NCT05593094
Version 7 to 8 · Hoffmann-La Roche
Patch inspector
Manual review pending.
arms_or_interventions_changecontact_admin_changeeligibility_criteria_changephase_changeprimary_outcome_any_changesecondary_outcome_any_change [
{
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"category": "timeline_actual_date_correction",
"new_type": "ACTUAL",
"old_type": "ACTUAL",
"severity": "low",
"direction": "earlier",
"new_value": "2020-09-03",
"old_value": "2020-10-15",
"delta_days": 42,
"date_struct": "startDateStruct",
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] 2a374afebd0beb926a805352620dfb031d9121a029edbd94e5e79c19df8bdb62/protocolSection/outcomesModule/primaryOutcomes/0/measure primary_outcome_any_change Any add/remove/replace under primary outcome measures is critical review priority. The Incidence of Treatment-Emergent Adverse Events of ZN-A-1041 as a monotherapy in Phase 1a
The Incidence of Treatment-emergent Adverse Events of ZN-A-1041 as a Monotherapy in Phase 1a
/protocolSection/outcomesModule/primaryOutcomes/0/description primary_outcome_any_change Any add/remove/replace under primary outcome measures is critical review priority. Dose at which no more than one out of six patient at the same dose level experiences a probable drug-related dose limiting toxicity.
Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.
/protocolSection/outcomesModule/primaryOutcomes/1/measure primary_outcome_any_change Any add/remove/replace under primary outcome measures is critical review priority. The Incidence of Treatment-Emergent Adverse Events of ZN-A-1041 in combination with T-DM1 or with T-DXd, or in combination with PHESGO or Herceptin plus Perjeta
The Incidence of Treatment-emergent Adverse Events of ZN-A-1041 in Combination with T-DM1 or with T-DXd, or in Combination with PHESGO or Herceptin plus Perjeta
/protocolSection/outcomesModule/primaryOutcomes/1/description primary_outcome_any_change Any add/remove/replace under primary outcome measures is critical review priority. Dose at which no more than one out of six patient at the same dose level experiences a probable drug-related dose limiting toxicity.
Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.
/protocolSection/outcomesModule/primaryOutcomes/2/measure primary_outcome_any_change Any add/remove/replace under primary outcome measures is critical review priority. RP2D Dose
RP2D
/protocolSection/outcomesModule/primaryOutcomes/2/description primary_outcome_any_change Any add/remove/replace under primary outcome measures is critical review priority. To evaluate the safety of ZN-A-1041 in combination with T-DM1 or with T-DXd, or in combination with PHESGO or Herceptin plus Perjeta in patients on the RP2D Dose
To evaluate the safety of ZN-A-1041 in combination with T-DM1 or with T-DXd, or in combination with PHESGO or Herceptin plus Perjeta in participants on the RP2D.
/protocolSection/outcomesModule/primaryOutcomes/2/timeFrame primary_outcome_any_change Any add/remove/replace under primary outcome measures is critical review priority. through study completion, an average of 1 year
Through study completion, an average of 1 year
/protocolSection/designModule/phases/1 phase_change Trial phase changes are high review-priority design changes. PHASE2
/protocolSection/armsInterventionsModule/armGroups/0/label arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 50mg
1a: ZN-A-1041
/protocolSection/armsInterventionsModule/armGroups/0/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. <p>Phase 1a:</p><p>Subjects will be given ZN-A-1041 orally 50mg Bid, for 21days as one cycle</p>
<p>Phase 1a:</p><p>Participants will receive escalating doses of ZN-A-1041 orally twice a day (BID) at pre-defined dosing regimens to determine the maximum tolerated dose (MTD).</p>
/protocolSection/armsInterventionsModule/armGroups/0/interventionNames/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. Drug: ZN-A-1041 50mg BID
Drug: ZN-A-1041
/protocolSection/armsInterventionsModule/armGroups/1/label arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 100mg
1b: ZN-A-1041 + T-DM1 3.6 mg/kg iv.
/protocolSection/armsInterventionsModule/armGroups/1/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. <p>Phase 1a:</p><p>Subjects will be given ZN-A-1041 orally 100mg Bid, for 21days as one cycle</p>
<p>Phase 1b Arm1:</p><ol><li>If the maximum tolerated dose (MTD) of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2).</li><li>If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.</li></ol>
/protocolSection/armsInterventionsModule/armGroups/1/interventionNames/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. Drug: ZN-A-1041 100mg BID
Drug: ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1b
/protocolSection/armsInterventionsModule/armGroups/2/label arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 200mg
1b: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.
/protocolSection/armsInterventionsModule/armGroups/2/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. <p>Phase 1a:</p><p>Subjects will be given ZN-A-1041 orally 200mg Bid, for 21days as one cycle</p>
<p>Phase 1b Arm2:</p><ol><li>If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2).</li><li>If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.</li></ol>
/protocolSection/armsInterventionsModule/armGroups/2/interventionNames/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. Drug: ZN-A-1041 200mg BID
Drug: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1b
/protocolSection/armsInterventionsModule/armGroups/3/label arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 400mg
1b: ZN-A-1041 + PHESGO / Herceptin plus Perjeta
/protocolSection/armsInterventionsModule/armGroups/3/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. <p>Phase 1a:</p><p>Subjects will be given ZN-A-1041 orally 400mg Bid, for 21days as one cycle</p>
<p>Phase 1b Arm3:</p><ol><li>If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2).</li><li>If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.</li></ol>
/protocolSection/armsInterventionsModule/armGroups/3/interventionNames/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. Drug: ZN-A-1041 400mg BID
Drug: ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1b
/protocolSection/armsInterventionsModule/armGroups/4/label arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 600mg
1c: ZN-A-1041 + T-DM1 3.6 mg/kg iv.
/protocolSection/armsInterventionsModule/armGroups/4/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. <p>Phase 1a:</p><p>Subjects will be given ZN-A-1041 orally 600mg Bid, for 21days as one cycle</p>
<p>Phase 1c Arm1:</p><p>The recommended dose combination for Phase 1c will be determined by the Investigator and the Sponsor based on the data from Phase 1b.</p>
/protocolSection/armsInterventionsModule/armGroups/4/interventionNames/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. Drug: ZN-A-1041 600mg BID
Drug: ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1c
/protocolSection/armsInterventionsModule/armGroups/5/label arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 800mg
1c: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.
/protocolSection/armsInterventionsModule/armGroups/5/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. <p>Phase 1a:</p><p>Subjects will be given ZN-A-1041 orally 800mg Bid, for 21days as one cycle</p>
<p>Phase 1c Arm2:</p><p>The recommended dose combination for Phase 1c will be determined by the Investigator and the Sponsor based on the data from Phase 1b.</p>
/protocolSection/armsInterventionsModule/armGroups/5/interventionNames/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. Drug: ZN-A-1041 800mg BID
Drug: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1c
/protocolSection/armsInterventionsModule/armGroups/6/label arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 1000mg
1c: ZN-A-1041 + Herceptin plus Perjeta/PHESGO
/protocolSection/armsInterventionsModule/armGroups/6/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. <p>Phase 1a:</p><p>Subjects will be given ZN-A-1041 orally 1000mg Bid, for 21days as one cycle</p>
<p>Phase 1c Arm3:</p><p>The recommended dose combination for Phase 1c will be determined by the Investigator and the Sponsor based on the data from Phase 1b.</p>
/protocolSection/armsInterventionsModule/armGroups/6/interventionNames/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. Drug: ZN-A-1041 1000mg BID
Drug: ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1c
/protocolSection/armsInterventionsModule/armGroups/7 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. {
"type": "EXPERIMENTAL",
"label": "1b: ZN-A-1041 + T-DM1 3.6 mg/kg iv.",
"description": "<p>Phase 1b Arm1:</p><ol><li>If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2)</li><li>If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.</li></ol>",
"interventionNames": [
"Drug: ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase1b"
]
} /protocolSection/armsInterventionsModule/armGroups/7 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. {
"type": "EXPERIMENTAL",
"label": "1b: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.",
"description": "<p>Phase 1b Arm2:</p><ol><li>If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2)</li><li>If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.</li></ol>",
"interventionNames": [
"Drug: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase1b"
]
} /protocolSection/armsInterventionsModule/armGroups/7 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. {
"type": "EXPERIMENTAL",
"label": "1b: ZN-A-1041 + PHESGO / Herceptin plus Perjeta",
"description": "<p>Phase 1b Arm3:</p><ol><li>If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2)</li><li>If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.</li></ol>",
"interventionNames": [
"Drug: ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase1b"
]
} /protocolSection/armsInterventionsModule/armGroups/7 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. {
"type": "EXPERIMENTAL",
"label": "1c: ZN-A-1041 + T-DM1 3.6 mg/kg iv.",
"description": "<p>Phase 1c Arm1:</p><p>The dose levels of ZN-A-1041 in the Phase 1c study will be the recommended doses determined in the Phase 1b study.</p>",
"interventionNames": [
"Drug: ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase1c"
]
} /protocolSection/armsInterventionsModule/armGroups/7 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. {
"type": "EXPERIMENTAL",
"label": "1c: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.",
"description": "<p>Phase 1c Arm2:</p><p>The dose levels of ZN-A-1041 in the Phase 1c study will be the recommended doses determined in the Phase 1b study.</p>",
"interventionNames": [
"Drug: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase1c"
]
} /protocolSection/armsInterventionsModule/armGroups/7 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. {
"type": "EXPERIMENTAL",
"label": "1c: ZN-A-1041 + Herceptin plus Perjeta/PHESGO",
"description": "<p>Phase 1c Arm3:</p><p>The dose levels of ZN-A-1041 in the Phase 1c study will be the recommended doses determined in the Phase 1b study.</p>",
"interventionNames": [
"Drug: ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase1c"
]
} /protocolSection/armsInterventionsModule/interventions/0/name arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 50mg BID
ZN-A-1041
/protocolSection/armsInterventionsModule/interventions/0/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. twice a day (BID) via oral administration
ZN-A-1041: escalating doses orally BID at pre-defined dosing regimens to determine the MTD
/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 50mg
1a: ZN-A-1041
/protocolSection/armsInterventionsModule/interventions/1/name arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 100mg BID
ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1b
/protocolSection/armsInterventionsModule/interventions/1/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. twice a day (BID) via oral administration
ZN-A-1041: BID via oral administration T-DM1: 3.6 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
/protocolSection/armsInterventionsModule/interventions/1/armGroupLabels/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 100mg
1b: ZN-A-1041 + T-DM1 3.6 mg/kg iv.
/protocolSection/armsInterventionsModule/interventions/2/name arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 200mg BID
ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1b
/protocolSection/armsInterventionsModule/interventions/2/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. twice a day (BID) via oral administration
ZN-A-1041: BID via oral administration T-DXd: 5.4 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
/protocolSection/armsInterventionsModule/interventions/2/armGroupLabels/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 200mg
1b: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.
/protocolSection/armsInterventionsModule/interventions/3/name arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 400mg BID
ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1b
/protocolSection/armsInterventionsModule/interventions/3/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. twice a day (BID) via oral administration
ZN-A-1041: BID via oral administration PHESGO dose is 600 mg pertuzumab/600 mg trastuzumab/2000 unites hyaluronidase every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta is 420 mg administered as an intravenous infusion Herceptin is 6 mg/kg administered as an intravenous infusion
/protocolSection/armsInterventionsModule/interventions/3/armGroupLabels/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 400mg
1b: ZN-A-1041 + PHESGO / Herceptin plus Perjeta
/protocolSection/armsInterventionsModule/interventions/4/name arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 600mg BID
ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1c
/protocolSection/armsInterventionsModule/interventions/4/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. twice a day (BID) via oral administration
ZN-A-1041: BID via oral administration T-DM1: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
/protocolSection/armsInterventionsModule/interventions/4/armGroupLabels/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 600mg
1c: ZN-A-1041 + T-DM1 3.6 mg/kg iv.
/protocolSection/armsInterventionsModule/interventions/5/name arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 800mg BID
ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1c
/protocolSection/armsInterventionsModule/interventions/5/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. twice a day (BID) via oral administration
ZN-A-1041: BID via oral administration T-DXd: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
/protocolSection/armsInterventionsModule/interventions/5/armGroupLabels/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 800mg
1c: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.
/protocolSection/armsInterventionsModule/interventions/6/name arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 1000mg BID
ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1c
/protocolSection/armsInterventionsModule/interventions/6/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. twice a day (BID) via oral administration
ZN-A-1041: BID via oral administration PHESGO: every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta: intravenous infusion Herceptin: intravenous infusion
/protocolSection/armsInterventionsModule/interventions/6/armGroupLabels/0 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. ZN-A-1041 1000mg
1c: ZN-A-1041 + Herceptin plus Perjeta/PHESGO
/protocolSection/armsInterventionsModule/interventions/7 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. {
"name": "ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase1b",
"type": "DRUG",
"otherNames": [
"ZN-A-1041 Enteric Capsules"
],
"description": "ZN-A-1041: twice a day (BID) via oral administration T-DM1: 3.6 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)",
"armGroupLabels": [
"1b: ZN-A-1041 + T-DM1 3.6 mg/kg iv."
]
} /protocolSection/armsInterventionsModule/interventions/7 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. {
"name": "ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase1b",
"type": "DRUG",
"otherNames": [
"ZN-A-1041 Enteric Capsules"
],
"description": "ZN-A-1041: twice a day (BID) via oral administration T-DXd: 5.4 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)",
"armGroupLabels": [
"1b: ZN-A-1041 + T-Dxd 5.4 mg/kg iv."
]
} /protocolSection/armsInterventionsModule/interventions/7 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. {
"name": "ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase1b",
"type": "DRUG",
"otherNames": [
"ZN-A-1041 Enteric Capsules"
],
"description": "ZN-A-1041: twice a day (BID) via oral administration PHESGO dose is 600 mg pertuzumab/600 mg trastuzumab/2000 unites hyaluronidase every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta is 420 mg administered as an intravenous infusion Herceptin is 6 mg/kg administered as an intravenous infusion",
"armGroupLabels": [
"1b: ZN-A-1041 + PHESGO / Herceptin plus Perjeta"
]
} /protocolSection/armsInterventionsModule/interventions/7 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. {
"name": "ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase1c",
"type": "DRUG",
"otherNames": [
"ZN-A-1041 Enteric Capsules"
],
"description": "ZN-A-1041: twice a day (BID) via oral administration T-DM1: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)",
"armGroupLabels": [
"1c: ZN-A-1041 + T-DM1 3.6 mg/kg iv."
]
} /protocolSection/armsInterventionsModule/interventions/7 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. {
"name": "ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase1c",
"type": "DRUG",
"otherNames": [
"ZN-A-1041 Enteric Capsules"
],
"description": "ZN-A-1041: twice a day (BID) via oral administration T-DXd: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)",
"armGroupLabels": [
"1c: ZN-A-1041 + T-Dxd 5.4 mg/kg iv."
]
} /protocolSection/armsInterventionsModule/interventions/7 arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. {
"name": "ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase1c",
"type": "DRUG",
"otherNames": [
"ZN-A-1041 Enteric Capsules"
],
"description": "ZN-A-1041: twice a day (BID) via oral administration PHESGO: every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta: intravenous infusion Herceptin: intravenous infusion",
"armGroupLabels": [
"1c: ZN-A-1041 + Herceptin plus Perjeta/PHESGO"
]
} /protocolSection/eligibilityModule/eligibilityCriteria eligibility_criteria_change Eligibility criteria changes can alter the studied population. <ul><li><p>Inclusion Criteria:</p><ol><li>ECOG performance status of 0 to 1</li><li>HER2 positive is defined as Immunohistochemistry (IHC) (++) and Fluorescence In Situ Hybridization (FISH) positive, or IHC (+++).</li><li><p>Phase 1a study will enroll patients with unresectable or metastatic HER2-positive advanced solid tumor.</p><p>For patients who have no brain metastases, the following criteria should be met:</p><ol><li>Patients should be relapsed or refractory to existing therapy(ies) or have been intolerant of such therapies</li><li>Patients with HER2-positive breast cancer should have previously received Trastuzumab, Pertuzumab, Trastuzumab emtansine(T-DM1) and a taxane.</li><li>Patients with HER2-positive gastric cancer must have previously received trastuzumab.</li><li>Have measurable or non-measurable disease assessable by RECIST 1.1.</li></ol><p>For patients with brain metastasis, the following criteria should be met:</p><ol><li>Patients with HER2-positive breast cancer must have received prior treatment with Trastuzumab, Pertuzumab and T-DM1, and a taxane or patient declined the above treatment.</li><li>Patients with HER2-positive gastric cancer must have previously received Trastuzumab</li><li>Do not require immediate local treatment during the trial period, and meet either of the following two criteria: i) For patients who have received previous local treatment (surgery, whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS)) for brain metastases, stable or progression of intracranial lesions is required. Interval from prior local therapy could be 3 weeks from WBRT and 2 weeks from SRS; ii) Symptomatic or not, patient has not received previous local treatment (surgery or radiotherapy) for brain metastases as long as no local therapy is needed during the trial period.</li></ol><p>For patients who have received previous tyrosine kinase inhibitor (TKI) treatment, chemotherapy, antibody, or antibody-drug conjugate (ADC), the interval between the last treatment and the first administration of the study drug in this trial should be at least 2 weeks.</p></li><li><p>Phase 1b and Phase 1c study will enroll patients with unresectable locally advanced or metastatic HER2+ breast cancer.</p><p>For Phase 1b patients who have no brain metastases, the following criteria should be met:</p><ol><li>For arm 1 and arm 2, patients should be relapsed or refractory to existing therapy(ies), with a history of prior treatment with trastuzumab and a taxane. For arm3, patients have received 4-8 cycles (21-day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression.</li><li>Have measurable or non-measurable disease assessable by RECIST 1.1</li></ol><p>For Phase 1c patients who have no brain metastases, the following criteria should be met:</p><ol><li>For arm 1 and arm 2, patients should be refractory to existing therapy(ies), with a history of prior treatment with trastuzumab. For arm3, patients have received a pertuzumab plus trastuzumab or T-DXd for advanced HER2+breast cancer with no evidence of disease progression.</li><li>In arms 1 and 2, patients should have at least one measurable lesion either extracranially or intracranially per RECIST v1.1.</li></ol><p>For patients with brain metastasis, the following criteria should be met:</p><ol><li>For arm 1 and arm 2 of phase 1b, patients should be relapsed or refractory to existing therapy(ies), with a history of prior treatment with trastuzumab and a taxane. For arm3, patients have received 4-8 cycles (21-day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression. For arm 1 and arm 2 of phase 1c, patients should be refractory to existing therapy(ies), with a history of prior treatment with trastuzumab. For arm3, patients have received previous treatment with a pertuzumab plus trastuzumab or T-DXd for advanced HER2+ breast cancer with no evidence of disease progression (except brain metastases).</li><li>Do not require immediate local treatment during the trial period, and meet either of the following two criteria: i) For patients who have received previous local treatment (surgery, whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS)) for brain metastases, stable or progression of intracranial lesions is required. Interval from prior local therapy could be 3 weeks from WBRT, 2 weeks from SRS and 4 weeks from surgery; ii) Symptomatic or not, patient has not received previous local treatment (surgery or radiotherapy) for brain metastases as long as no local therapy is needed during the trial period.</li></ol></li><li>Suspected or confirmed leptomeningeal metastasis are allowed.</li><li>In Phase 1b arm1 and arm2, patients who have received previous tyrosine kinase inhibitor (TKI) treatment, chemotherapy, antibody, or antibody-drug conjugate (ADC), the interval between the last treatment and the first administration of the study drug in this trial should be at least 2 weeks. For arm3, patients should not have prior treatment for unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis, except for ongoing Herceptin, Perjeta or PHESGO and taxane.</li><li>In Phase 1c arm1 and arm2, Patients should not have received prior treatment with tucatinib, afatinib, or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib or neratinib within 12 months of starting study treatment (except in cases where they were given for ≤ 21 days and was discontinued for reasons other than disease progression or severe toxicity). Prior treatment with pyrotinib for recurrent of mBC (except in cases where pyrotinib was given for ≤ 21 days and was discontinued for reasons other than disease progression or severe toxicity). For arm3, patients should not have prior treatment for unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis, except for ongoing Herceptin, Perjeta or PHESGO or T-Dxd based induction.</li></ol></li><li><p>Exclusion Criteria:</p><ol><li>Subjects who have participated in any clinical study or received any clinical study drug within 4 weeks prior to the first administration except for on-going Herceptin, Perjeta or PHESGO in arm3</li><li><p>CNS Exclusion - Based on screening brain MRI and clinical assessment</p><ol><li>Progressive neurologic impairment or increased intracranial pressure (including nausea, vomiting, blurred vision, headache, epilepsy, etc.)</li><li>Any intracranial lesion thought to require immediate local therapy</li><li>Require antiepileptic treatment (except for these patients with stable seizures require continuous Levetiracetam therapy).</li><li>Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent)</li></ol></li></ol></li></ul>
<p>Inclusion Criteria:</p><ul><li>Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1</li><li>Life expectancy of at least 6 months, as determined by the investigator</li><li>Histologically or cytologically confirmed with unresectable or metastatic HER2-positive advanced solid tumors</li><li>Must be relapsed or refractory after prior treatment for metastatic disease that included a taxane and trastuzumab or must have received first-line induction therapy for advanced disease a pertuzumab plus trastuzumab-based regimen or a T-DXd-based regimen</li><li>Participants with new, untreated, progressive, or stable brain metastases are eligible</li></ul><p>Exclusion Criteria:</p><ul><li>Participation in any other clinical study involving an investigational drug or device within 4 weeks prior to the first dose of study treatment</li><li>Any intracranial lesion (brain metastasis) that requires immediate local therapy, such as surgery or radiation, or systemic corticosteroids at the time of enrollment</li></ul>
/protocolSection/outcomesModule/secondaryOutcomes/0/measure secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Plasma, urine and potentially CSF level of ZN-A-1041 and its main metabolites
Plasma, Urine and Potentially Cerebrospinal Fluid (CSF) Level of ZN-A-1041 and its Main Metabolites
/protocolSection/outcomesModule/secondaryOutcomes/0/description secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. To assess the PK of ZN-A-1041 and its major metabolites
To assess the PK of ZN-A-1041 and its major metabolites.
/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. From baseline to Cycle 9 (each cycel is 21 days)
From baseline to cycle 9 (each cycel is 21 days)
/protocolSection/outcomesModule/secondaryOutcomes/1/measure secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Serum level of combination drugs in phase 1c
Serum Level of Combination Drugs in Phase 1c
/protocolSection/outcomesModule/secondaryOutcomes/1/description secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. To assess the serum concentration of combination drugs
To assess the serum concentration of combination drugs.
/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. through study completion, an average of 2 year
Through study completion, an average of 2 year
/protocolSection/outcomesModule/secondaryOutcomes/2/measure secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Anti-drug antibodies (ADAs) evaluation in Phase 1c
Anti-drug Antibodies (ADAs) Evaluation in Phase 1c
/protocolSection/outcomesModule/secondaryOutcomes/2/description secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. To assess the incidence of ADAs
To assess the incidence of ADAs.
/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. through study completion, an average of 2 year
Through study completion, an average of 2 year
/protocolSection/outcomesModule/secondaryOutcomes/3/measure secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. overall Response Rate (ORR)
Overall Response Rate (ORR)
/protocolSection/outcomesModule/secondaryOutcomes/3/description secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a,phase 1b and 1c
The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a, Phase 1b and 1c.
/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. through study completion, an average of 2 year
Through study completion, an average of 2 year
/protocolSection/outcomesModule/secondaryOutcomes/4/measure secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Progression free survival(PFS)
Progression Free Survival (PFS)
/protocolSection/outcomesModule/secondaryOutcomes/4/description secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a,phase 1b and 1c
The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a, Phase 1b and 1c.
/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. through study completion, an average of 2 year
Through study completion, an average of 2 year
/protocolSection/statusModule/startDateStruct/date start_timeline_change Start date changes are operational timeline signals. 2020-10-15
2020-09-03
/protocolSection/contactsLocationsModule/centralContacts contact_admin_change Central contact updates are usually administrative. [
{
"name": "Ding Zhou, Ph.D",
"role": "CONTACT",
"email": "ding.zhou@zionpharma.com",
"phone": "(86)-13916360900"
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] /protocolSection/contactsLocationsModule/overallOfficials/0/name Anders Carey K, MD
Clinical Trials
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Hoffmann-La Roche
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STUDY_DIRECTOR
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Arizona Clinical Research Center, Inc.;Hematology Oncology Physicians - Aoa
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85712
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{
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UCSF Helen Diller Family CCC
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San Francisco
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94158
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37.77493
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Dana Farber Cancer Institute
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University of Michigan Hospital
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Ann Arbor
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48109
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42.27756
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Barbara Ann Karmanos Cancer Institute
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Detroit
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Michigan
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48201
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42.33143
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Duke University School of Medicine
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Durham
/protocolSection/contactsLocationsModule/locations/6/state Texas
North Carolina
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27710
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MD Anderson Cancer Center
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Houston
/protocolSection/contactsLocationsModule/locations/7/state Victoria
Texas
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77030-4000
/protocolSection/contactsLocationsModule/locations/7/country Australia
United States
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29.76328
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Geelong Hospital
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Geelong
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3220
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Sunshine Hospital
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St Albans
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Victoria
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3021
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Australia
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EDOG - Institut Claudius Regaud - PPDS
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Toulouse
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31059
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Centre Georges Francois Leclerc
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Dijon
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21000
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Centre Oscar Lambret
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Lille
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59020
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France
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50.63391
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3.05512
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Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
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Lyon
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69373
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France
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45.74906
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4.84789
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Institut Paoli-Calmettes
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Marseille
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13009
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France
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43.29695
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Institut de Cancerologie de l Ouest
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Saint-Herblain
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44805
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France
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47.21154
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Gustave Roussy
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Villejuif
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94800
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France
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48.7939
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2.35992
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Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l - PPDS
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Parma
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43126
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Italy
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44.79935
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10.32618
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Asst Papa Giovanni XXIII
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Bergamo
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24127
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Italy
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9.66721
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Fondazione Policlinico Universitario A Gemelli-Rome
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Magnago
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20020
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Italy
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Auckland City Hospital
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Auckland
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1023
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New Zealand
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Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON
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Argentona
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08310
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2.40114
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Hospital Clinico Universitario de Santiago
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Santiago de Compostela
/protocolSection/contactsLocationsModule/locations/22/state Lancashire
LA Coruna
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15706
/protocolSection/contactsLocationsModule/locations/22/country United Kingdom
Spain
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42.88052
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}
} /protocolSection/contactsLocationsModule/locations/27 {
"zip": "23007",
"city": "Jaén",
"country": "Spain",
"facility": "Hospital Universitario de Jaen",
"geoPoint": {
"lat": 37.76922,
"lon": -3.79028
}
} /protocolSection/contactsLocationsModule/locations/28 {
"zip": "28007",
"city": "Madrid",
"country": "Spain",
"facility": "Hospital Beata Maria Ana",
"geoPoint": {
"lat": 40.4165,
"lon": -3.70256
}
} /protocolSection/contactsLocationsModule/locations/29 {
"zip": "28040",
"city": "Madrid",
"country": "Spain",
"facility": "Hospital Clinico San Carlos",
"geoPoint": {
"lat": 40.4165,
"lon": -3.70256
}
} /protocolSection/contactsLocationsModule/locations/30 {
"zip": "28041",
"city": "Madrid",
"country": "Spain",
"facility": "Hospital Universitario 12 de Octubre",
"geoPoint": {
"lat": 40.4165,
"lon": -3.70256
}
} /protocolSection/contactsLocationsModule/locations/31 {
"zip": "41009",
"city": "Seville",
"country": "Spain",
"facility": "Hospital Universitario Virgen Macarena",
"geoPoint": {
"lat": 37.38283,
"lon": -5.97317
}
} /protocolSection/contactsLocationsModule/locations/32 {
"zip": "46009",
"city": "Valencia",
"country": "Spain",
"facility": "Fundacion Instituto Valenciano de Oncologia (IVO)",
"geoPoint": {
"lat": 39.47391,
"lon": -0.37966
}
} /protocolSection/contactsLocationsModule/locations/33 {
"zip": "46010",
"city": "Valencia",
"country": "Spain",
"facility": "Hospital Clinico Universitario de Valencia",
"geoPoint": {
"lat": 39.47391,
"lon": -0.37966
}
} /protocolSection/contactsLocationsModule/locations/34 {
"zip": "M20 4BX",
"city": "Manchester",
"state": "Lancashire",
"country": "United Kingdom",
"facility": "The Christie",
"geoPoint": {
"lat": 53.48095,
"lon": -2.23743
}
} /protocolSection/contactsLocationsModule/locations/35 {
"zip": "L69 3GL",
"city": "Liverpool",
"state": "Merseyside",
"country": "United Kingdom",
"facility": "Clatterbridge Cancer Centre",
"geoPoint": {
"lat": 53.41058,
"lon": -2.97794
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} /protocolSection/statusModule/statusVerifiedDate 2024-08
2025-08
/protocolSection/statusModule/lastUpdateSubmitDate 2024-08-29
2025-08-28
/protocolSection/statusModule/lastUpdatePostDateStruct/date 2024-09-03
2025-09-04
/protocolSection/descriptionModule/briefSummary <p>This will be a Phase 1, multicenter, open-label trial to evaluate the safety, tolerability, PK and efficacy of ZN-A-1041 as a monotherapy or in combination in patients with HER2-positive advanced solid tumors with or without brain metastases.</p><p>The study will consist of three phases: Phase 1a (dose escalation with ZN-A-1041 monotherapy), Phase 1b (dose escalation with ZN-A-1041 combination therapy) and Phase 1c (dose expansion with ZN-A-1041 combination therapy).</p>
<p>This will be a Phase 1, multicenter, open-label trial to evaluate the safety, tolerability, PK and efficacy of ZN-A-1041 as a monotherapy or in combination in participants with HER2-positive advanced solid tumors with or without brain metastases.</p><p>The study will consist of three phases: Phase 1a (dose escalation with ZN-A-1041 monotherapy), Phase 1b (dose escalation with ZN-A-1041 combination therapy) and Phase 1c (dose expansion with ZN-A-1041 combination therapy).</p>
/protocolSection/descriptionModule/detailedDescription <p>Phase 1a of the study will adopt the "modified 3+3" dose escalation design with a total of 7 planned dose levels. Patients with HER2-positive advanced solid tumor (including those with brain metastases) will be enrolled to receive a single-dose administration of ZN-A-1041 followed by multiple-dose administration of ZN-A-1041.Phase 1b of the study will adopt the "traditional 3+3" dose escalation design. The dose levels will be based on the results of the Phase 1a study and the results of a food effect study. In Phase 1b, patients with unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis will be enrolled in three arms: Arm1 will receive multiple doses of ZN-A-1041 in combination with T-DM1; Arm2 will receive multiple doses of ZN-A-1041 in combination with T-DXd. Arm 3 will receive multiple doses of ZN-A-1041 in combination with PHESGO or Herceptin plus Perjeta after Herceptin plus Perjeta and 4-8-cycle treatment of taxane. Patients will be assessed for an appropriate arm by the sponsor and the investigator at the time of consent. Patients with unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis are planned to be enrolled in Phase 1c of the study: Arm1 will receive multiple doses of ZN-A-1041 in combination with T-DM1; Arm2 will receive multiple doses of ZN-A-1041 in combination with T-DXd; Arm 3 will receive multiple doses of ZN-A-1041 in combination with PHESGO or Herceptin plus Perjeta after Herceptin plus Perjeta or T-DXd based induction regimen. Patients will be assessed for an appropriate arm by the sponsor and the investigator at the time of consent. Arm1 of Phase 1c can start independently after the DLT observation period of the last patient in Phase 1b Arm1. Arm 2 of Phase 1c can start independently after the DLT observation of the last patient in Phase 1b Arm 2. Arm 3 of Phase 1c can start independently after the DLT observation of the last patient in Phase 1b Arm 3. The dose levels used in Phase 1c will be based on the recommended doses obtained from the Phase 1b study.</p><p>Each phase of the study includes a screening period (from 28 days prior to the first administration of the study drug), a treatment period (until there are no clinical benefits as deemed by the Investigator, disease progression, death, intolerable toxicity, withdrawal of informed consent, loss of follow-up, or the start of new anti-tumor treatment), and a follow-up period (until 28 days after the last administration of the study drug). During the trial, the safety, tolerability, PK and efficacy data of ZN-A-1041 as monotherapy and in combination in the subjects will be collected and analyzed, thereby providing RP2D for subsequent future clinical trials.</p>
<p>This study is composed of three parts designed to evaluate the safety and efficacy of ZN-A-1041 in participants with HER2-positive advanced solid tumors.</p><p>Phase 1a (Monotherapy Dose Escalation): In this first phase, participants will receive ZN-A-1041 alone. The study will begin with a low dose of ZN-A-1041, which will be gradually increased in new groups of participants to find the highest dose that can be given safely. This will establish the recommended dose for further study.</p><p>Phase 1b (Combination Dose Escalation): In the second phase, the study will evaluate the safety of giving ZN-A-1041 together with established standard-of-care therapies for HER2-positive breast cancer. Participants will be enrolled into one of three combination arms to receive ZN-A-1041 with either T-DM1, T-DXd, or a pertuzumab/trastuzumab-based regimen. This phase will identify the recommended dose for these combination therapies.</p><p>Phase 1c (Combination Dose Expansion): In the final phase, additional participants will be enrolled to receive ZN-A-1041 at the recommended combination doses identified in Phase 1b. This will allow for a more thorough evaluation of the safety and preliminary efficacy of these treatment regimens.</p><p>Throughout the study, participants will undergo screening, treatment, and follow-up periods to collect comprehensive data on the safety, tolerability, pharmacokinetics, and anti-tumor activity of ZN-A-1041, both as a single agent and in combination.</p>
/protocolSection/ipdSharingStatementModule {
"ipdSharing": "YES",
"description": "For eligible studies, qualified researchers may request access to individual patient level clinical data.\nSee Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing"
} /protocolSection/identificationModule/orgStudyIdInfo/id ZN-A-1041-101-US
XO45189
/protocolSection/identificationModule/organization/fullName Suzhou Zanrong Pharma Limited
Hoffmann-La Roche
/protocolSection/identificationModule/briefTitle A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Patients With HER2-Positive Advanced Solid Tumors
A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Solid Tumors
/protocolSection/identificationModule/officialTitle A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ZN-A-1041 Enteric Capsules as a Single Agent or in Combination in Patients With HER2-Positive Advanced Solid Tumors
A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Efficacy of ZN-A-1041 Enteric Capsules as a Single Agent or in Combination in Patients With HER2-Positive Advanced Solid Tumors
/protocolSection/identificationModule/secondaryIdInfos [
{
"id": "ZN-A-1041-101-US",
"type": "OTHER",
"domain": "Suzhou Zanrong Pharma Limited"
},
{
"id": "2023-508459-37-00",
"type": "CTIS"
}
] /protocolSection/sponsorCollaboratorsModule/leadSponsor/name Suzhou Zanrong Pharma Limited
Hoffmann-La Roche
/protocolSection/statusModule/overallStatus RECRUITING
ACTIVE_NOT_RECRUITING
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"value": "<p>This study is composed of three parts designed to evaluate the safety and efficacy of ZN-A-1041 in participants with HER2-positive advanced solid tumors.</p><p>Phase 1a (Monotherapy Dose Escalation): In this first phase, participants will receive ZN-A-1041 alone.\nThe study will begin with a low dose of ZN-A-1041, which will be gradually increased in new groups of participants to find the highest dose that can be given safely.\nThis will establish the recommended dose for further study.</p><p>Phase 1b (Combination Dose Escalation): In the second phase, the study will evaluate the safety of giving ZN-A-1041 together with established standard-of-care therapies for HER2-positive breast cancer.\nParticipants will be enrolled into one of three combination arms to receive ZN-A-1041 with either T-DM1, T-DXd, or a pertuzumab/trastuzumab-based regimen.\nThis phase will identify the recommended dose for these combination therapies.</p><p>Phase 1c (Combination Dose Expansion): In the final phase, additional participants will be enrolled to receive ZN-A-1041 at the recommended combination doses identified in Phase 1b.\nThis will allow for a more thorough evaluation of the safety and preliminary efficacy of these treatment regimens.</p><p>Throughout the study, participants will undergo screening, treatment, and follow-up periods to collect comprehensive data on the safety, tolerability, pharmacokinetics, and anti-tumor activity of ZN-A-1041, both as a single agent and in combination.</p>"
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"value": "<p>Phase 1b Arm2:</p><ol><li>If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2).</li><li>If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.</li></ol>"
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"value": "<p>Phase 1b Arm3:</p><ol><li>If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2).</li><li>If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.</li></ol>"
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},
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},
{
"op": "replace",
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},
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},
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"op": "replace",
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"value": "Plasma, Urine and Potentially Cerebrospinal Fluid (CSF) Level of ZN-A-1041 and its Main Metabolites"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/0/description",
"value": "To assess the PK of ZN-A-1041 and its major metabolites."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame",
"value": "From baseline to cycle 9 (each cycel is 21 days)"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/1/measure",
"value": "Serum Level of Combination Drugs in Phase 1c"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/1/description",
"value": "To assess the serum concentration of combination drugs."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
"value": "Through study completion, an average of 2 year"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/2/measure",
"value": "Anti-drug Antibodies (ADAs) Evaluation in Phase 1c"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/2/description",
"value": "To assess the incidence of ADAs."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
"value": "Through study completion, an average of 2 year"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/3/measure",
"value": "Overall Response Rate (ORR)"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/3/description",
"value": "The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a, Phase 1b and 1c."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
"value": "Through study completion, an average of 2 year"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/4/measure",
"value": "Progression Free Survival (PFS)"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/4/description",
"value": "The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a, Phase 1b and 1c."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame",
"value": "Through study completion, an average of 2 year"
},
{
"op": "replace",
"path": "/protocolSection/eligibilityModule/eligibilityCriteria",
"value": "<p>Inclusion Criteria:</p><ul><li>Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1</li><li>Life expectancy of at least 6 months, as determined by the investigator</li><li>Histologically or cytologically confirmed with unresectable or metastatic HER2-positive advanced solid tumors</li><li>Must be relapsed or refractory after prior treatment for metastatic disease that included a taxane and trastuzumab or must have received first-line induction therapy for advanced disease a pertuzumab plus trastuzumab-based regimen or a T-DXd-based regimen</li><li>Participants with new, untreated, progressive, or stable brain metastases are eligible</li></ul><p>Exclusion Criteria:</p><ul><li>Participation in any other clinical study involving an investigational drug or device within 4 weeks prior to the first dose of study treatment</li><li>Any intracranial lesion (brain metastasis) that requires immediate local therapy, such as surgery or radiation, or systemic corticosteroids at the time of enrollment</li></ul>"
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{
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},
{
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"value": "Hoffmann-La Roche"
},
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"value": "STUDY_DIRECTOR"
},
{
"op": "replace",
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},
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"path": "/protocolSection/contactsLocationsModule/locations/0/zip",
"value": "85712"
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{
"op": "remove",
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{
"op": "replace",
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"value": "UCSF Helen Diller Family CCC"
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{
"op": "remove",
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},
{
"op": "replace",
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"value": "San Francisco"
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/2/zip",
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{
"op": "remove",
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{
"op": "replace",
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{
"op": "remove",
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"op": "replace",
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{
"op": "replace",
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"op": "replace",
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"value": "Detroit"
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/5/state",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/5/zip",
"value": "48201"
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{
"op": "remove",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/5/geoPoint/lat",
"value": 42.33143
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/5/geoPoint/lon",
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},
{
"op": "replace",
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"value": "Durham"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/6/state",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/6/zip",
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{
"op": "remove",
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"op": "replace",
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"value": 35.99403
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/6/geoPoint/lon",
"value": -78.89862
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"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/7/facility",
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},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/7/city",
"value": "Houston"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/7/state",
"value": "Texas"
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"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/7/zip",
"value": "77030-4000"
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/7/country",
"value": "United States"
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/7/geoPoint/lat",
"value": 29.76328
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/7/geoPoint/lon",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/8/facility",
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{
"op": "replace",
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"value": "Geelong"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/8/zip",
"value": "3220"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/8/geoPoint/lat",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/8/geoPoint/lon",
"value": 144.36069
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/9/facility",
"value": "Sunshine Hospital"
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{
"op": "remove",
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},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/9/city",
"value": "St Albans"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/9/state",
"value": "Victoria"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/9/zip",
"value": "3021"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/9/country",
"value": "Australia"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/9/geoPoint/lat",
"value": -37.74496
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/9/geoPoint/lon",
"value": 144.80049
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/10/facility",
"value": "EDOG - Institut Claudius Regaud - PPDS"
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{
"op": "remove",
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},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/10/city",
"value": "Toulouse"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/10/zip",
"value": "31059"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/10/geoPoint/lat",
"value": 43.60426
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/10/geoPoint/lon",
"value": 1.44367
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{
"op": "add",
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{
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},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/11/city",
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},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/11/zip",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/11/geoPoint/lat",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/11/geoPoint/lon",
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"op": "replace",
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"op": "replace",
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{
"op": "replace",
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},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/12/country",
"value": "France"
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/12/geoPoint/lat",
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{
"op": "replace",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/13/facility",
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{
"op": "remove",
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},
{
"op": "replace",
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{
"op": "replace",
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{
"op": "replace",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/13/geoPoint/lat",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/13/geoPoint/lon",
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{
"op": "replace",
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{
"op": "replace",
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{
"op": "replace",
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},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/14/country",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/14/geoPoint/lat",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/14/geoPoint/lon",
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"op": "replace",
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{
"op": "replace",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/15/country",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/15/geoPoint/lat",
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{
"op": "replace",
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{
"op": "replace",
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"value": "Gustave Roussy"
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"op": "remove",
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},
{
"op": "replace",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/16/zip",
"value": "94800"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/16/country",
"value": "France"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/16/geoPoint/lat",
"value": 48.7939
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/16/geoPoint/lon",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/17/facility",
"value": "Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l - PPDS"
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{
"op": "remove",
"path": "/protocolSection/contactsLocationsModule/locations/17/status"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/17/city",
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},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/17/zip",
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},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/17/country",
"value": "Italy"
},
{
"op": "remove",
"path": "/protocolSection/contactsLocationsModule/locations/17/contacts"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/17/geoPoint/lat",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/17/geoPoint/lon",
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{
"op": "add",
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},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/18/facility",
"value": "Asst Papa Giovanni XXIII"
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{
"op": "remove",
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},
{
"op": "replace",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/18/zip",
"value": "24127"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/18/country",
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},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/18/geoPoint/lat",
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{
"op": "replace",
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"op": "add",
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"op": "replace",
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{
"op": "remove",
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{
"op": "replace",
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{
"op": "replace",
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{
"op": "replace",
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{
"op": "replace",
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"op": "replace",
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"op": "replace",
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{
"op": "replace",
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{
"op": "replace",
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"op": "replace",
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"op": "remove",
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{
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{
"op": "replace",
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"op": "replace",
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"op": "replace",
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{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/22/geoPoint/lat",
"value": 42.88052
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/22/geoPoint/lon",
"value": -8.54569
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/23",
"value": {
"zip": "32540",
"city": "A Gudiña",
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"country": "Spain",
"facility": "Hospital Universitario Ramon y Cajal",
"geoPoint": {
"lat": 42.06103,
"lon": -7.13875
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/24",
"value": {
"zip": "41730",
"city": "Las Cabezas de San Juan",
"state": "Sevilla",
"country": "Spain",
"facility": "Hospital Universitario Virgen del Rocio",
"geoPoint": {
"lat": 36.9838,
"lon": -5.93933
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/25",
"value": {
"zip": "08028",
"city": "Barcelona",
"country": "Spain",
"facility": "Instituto Oncologico Dr. Rosell-Hospital Universitari Dexeus-Grupo Quironsalud",
"geoPoint": {
"lat": 41.38879,
"lon": 2.15899
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/26",
"value": {
"zip": "08036",
"city": "Barcelona",
"country": "Spain",
"facility": "Hospital Clinic de Barcelona",
"geoPoint": {
"lat": 41.38879,
"lon": 2.15899
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/27",
"value": {
"zip": "23007",
"city": "Jaén",
"country": "Spain",
"facility": "Hospital Universitario de Jaen",
"geoPoint": {
"lat": 37.76922,
"lon": -3.79028
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/28",
"value": {
"zip": "28007",
"city": "Madrid",
"country": "Spain",
"facility": "Hospital Beata Maria Ana",
"geoPoint": {
"lat": 40.4165,
"lon": -3.70256
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/29",
"value": {
"zip": "28040",
"city": "Madrid",
"country": "Spain",
"facility": "Hospital Clinico San Carlos",
"geoPoint": {
"lat": 40.4165,
"lon": -3.70256
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/30",
"value": {
"zip": "28041",
"city": "Madrid",
"country": "Spain",
"facility": "Hospital Universitario 12 de Octubre",
"geoPoint": {
"lat": 40.4165,
"lon": -3.70256
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/31",
"value": {
"zip": "41009",
"city": "Seville",
"country": "Spain",
"facility": "Hospital Universitario Virgen Macarena",
"geoPoint": {
"lat": 37.38283,
"lon": -5.97317
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/32",
"value": {
"zip": "46009",
"city": "Valencia",
"country": "Spain",
"facility": "Fundacion Instituto Valenciano de Oncologia (IVO)",
"geoPoint": {
"lat": 39.47391,
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}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/33",
"value": {
"zip": "46010",
"city": "Valencia",
"country": "Spain",
"facility": "Hospital Clinico Universitario de Valencia",
"geoPoint": {
"lat": 39.47391,
"lon": -0.37966
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/34",
"value": {
"zip": "M20 4BX",
"city": "Manchester",
"state": "Lancashire",
"country": "United Kingdom",
"facility": "The Christie",
"geoPoint": {
"lat": 53.48095,
"lon": -2.23743
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/35",
"value": {
"zip": "L69 3GL",
"city": "Liverpool",
"state": "Merseyside",
"country": "United Kingdom",
"facility": "Clatterbridge Cancer Centre",
"geoPoint": {
"lat": 53.41058,
"lon": -2.97794
}
}
},
{
"op": "add",
"path": "/protocolSection/ipdSharingStatementModule",
"value": {
"ipdSharing": "YES",
"description": "For eligible studies, qualified researchers may request access to individual patient level clinical data.\nSee Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing"
}
}
]