NCT04482309

A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors

Version 28 to 29 · AstraZeneca

Patch inspector

Version 28 to 29

56 operations 7 path groups ctgov_internal_history

Severity is deterministic uncalibrated triage metadata, not validated review priority. Operation-level severity is inferred from deterministic path rules. Rule matches shown per operation are approximate previews (they skip the pipeline's suppression passes); the authoritative classification is the stored event record.

Plain-language summary

Manual review pending.

Rules fired

arms_or_interventions_changedesign_info_changeeligibility_criteria_changeprimary_outcome_any_changesecondary_outcome_any_change

Value signals

[
  {
    "path": "/protocolSection/statusModule/completionDateStruct/date",
    "signal": "timeline_significant_shift",
    "category": "timeline_significant_shift",
    "new_type": "ESTIMATED",
    "old_type": "ESTIMATED",
    "severity": "medium",
    "direction": "later",
    "new_value": "2027-07-30",
    "old_value": "2027-03-31",
    "delta_days": 121,
    "date_struct": "completionDateStruct",
    "new_precision": "day",
    "old_precision": "day"
  }
]

Provenance

Source: ctgov_internal_history
Fetched: 2026-06-18 19:00:24+00
Raw hash: 61ac586543459074003a4f7d2b23725f09c723f9c890863b953ba57177d23995
Payload: Source URL

Primary outcomes Outcome measures that define the trial's primary evidence target. Triage: Critical 1 ops

replace /protocolSection/outcomesModule/primaryOutcomes/0/timeFrame

Triage: Critical

Primary Outcome Change Operation 40

Matched rules

primary_outcome_any_change Any add/remove/replace under primary outcome measures is critical review priority.

Before

An average of approximately 41 months

After

An average of approximately 6 months

Design Trial model, phase, allocation, masking, arms, or interventions. Triage: High 32 ops

replace /protocolSection/designModule/designInfo/interventionModelDescription

Triage: High

Design Change Operation 8

Matched rules

design_info_change Design information changes can alter allocation, masking, model, or purpose and need review.

Before

This study will consist of seven cohorts of urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, Pancreatic cancer, and rare tumors.

After

This study will consist of Part 1 which includes 7 cohorts of: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors; and Part 2 which includes 5 cohorts A to E of: A) any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer), B) any tumor type that is HER2 IHC 2+&#x2F;ISH+ (excluding breast, gastric cancer, and colorectal cancer), C) HER2 IHC 2+ or 1+ endometrial cancer, D) HER2 IHC 2+ or 1+ ovarian cancer, and E) HER2 IHC 2+ or 1+ cervical cancer.

replace /protocolSection/armsInterventionsModule/armGroups/0/label

Triage: High

Arm Intervention Change Operation 9

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 1

After

Part 1 Cohort 1

replace /protocolSection/armsInterventionsModule/armGroups/0/description

Triage: High

Arm Intervention Change Operation 10

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Cohort 1: Biliary tract cancer

After

Biliary tract cancer

replace /protocolSection/armsInterventionsModule/armGroups/1/label

Triage: High

Arm Intervention Change Operation 11

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 2

After

Part 1 Cohort 2

replace /protocolSection/armsInterventionsModule/armGroups/1/description

Triage: High

Arm Intervention Change Operation 12

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Cohort 2: Bladder cancer

After

Bladder cancer

replace /protocolSection/armsInterventionsModule/armGroups/2/label

Triage: High

Arm Intervention Change Operation 13

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 3

After

Part 1 Cohort 3

replace /protocolSection/armsInterventionsModule/armGroups/2/description

Triage: High

Arm Intervention Change Operation 14

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Cohort 3: Cervical cancer

After

Cervical cancer

replace /protocolSection/armsInterventionsModule/armGroups/3/label

Triage: High

Arm Intervention Change Operation 15

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 4

After

Part 1 Cohort 4

replace /protocolSection/armsInterventionsModule/armGroups/3/description

Triage: High

Arm Intervention Change Operation 16

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Cohort 4: Endometrial cancer

After

Endometrial cancer

replace /protocolSection/armsInterventionsModule/armGroups/4/label

Triage: High

Arm Intervention Change Operation 17

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 5

After

Part 1 Cohort 5

replace /protocolSection/armsInterventionsModule/armGroups/4/description

Triage: High

Arm Intervention Change Operation 18

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Cohort 5: Ovarian cancer

After

Ovarian cancer

replace /protocolSection/armsInterventionsModule/armGroups/5/label

Triage: High

Arm Intervention Change Operation 19

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 6

After

Part 1 Cohort 6

replace /protocolSection/armsInterventionsModule/armGroups/5/description

Triage: High

Arm Intervention Change Operation 20

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Cohort 6: Pancreatic cancer

After

Pancreatic cancer

replace /protocolSection/armsInterventionsModule/armGroups/6/label

Triage: High

Arm Intervention Change Operation 21

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 7

After

Part 1 Cohort 7

replace /protocolSection/armsInterventionsModule/armGroups/6/description

Triage: High

Arm Intervention Change Operation 22

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Cohort 7: Rare tumors

After

Rare tumors

add /protocolSection/armsInterventionsModule/armGroups/7

Triage: High

Arm Intervention Change Operation 23

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

After

{
  "type": "EXPERIMENTAL",
  "label": "Part 2 Cohort A",
  "description": "Any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer)",
  "interventionNames": [
    "Drug: Trastuzumab deruxtecan"
  ]
}

add /protocolSection/armsInterventionsModule/armGroups/8

Triage: High

Arm Intervention Change Operation 24

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

After

{
  "type": "EXPERIMENTAL",
  "label": "Part 2 Cohort B",
  "description": "Any tumor type that is HER2 IHC 2+&#x2F;ISH+ (excluding breast, gastric cancer, and colorectal cancer)",
  "interventionNames": [
    "Drug: Trastuzumab deruxtecan"
  ]
}

add /protocolSection/armsInterventionsModule/armGroups/9

Triage: High

Arm Intervention Change Operation 25

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

After

{
  "type": "EXPERIMENTAL",
  "label": "Part 2 Cohort C",
  "description": "HER2 IHC 2+ or 1+ endometrial cancer",
  "interventionNames": [
    "Drug: Trastuzumab deruxtecan"
  ]
}

add /protocolSection/armsInterventionsModule/armGroups/10

Triage: High

Arm Intervention Change Operation 26

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

After

{
  "type": "EXPERIMENTAL",
  "label": "Part 2 Cohort D",
  "description": "HER2 IHC 2+ or 1+ ovarian cancer",
  "interventionNames": [
    "Drug: Trastuzumab deruxtecan"
  ]
}

add /protocolSection/armsInterventionsModule/armGroups/11

Triage: High

Arm Intervention Change Operation 27

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

After

{
  "type": "EXPERIMENTAL",
  "label": "Part 2 Cohort E",
  "description": "HER2 IHC 2+ or 1+ cervical cancer",
  "interventionNames": [
    "Drug: Trastuzumab deruxtecan"
  ]
}

replace /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/0

Triage: High

Arm Intervention Change Operation 28

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 1

After

Part 1 Cohort 1

replace /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/1

Triage: High

Arm Intervention Change Operation 29

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 2

After

Part 1 Cohort 2

replace /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/2

Triage: High

Arm Intervention Change Operation 30

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 3

After

Part 1 Cohort 3

replace /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/3

Triage: High

Arm Intervention Change Operation 31

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 4

After

Part 1 Cohort 4

replace /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/4

Triage: High

Arm Intervention Change Operation 32

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 5

After

Part 1 Cohort 5

replace /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/5

Triage: High

Arm Intervention Change Operation 33

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 6

After

Part 1 Cohort 6

replace /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/6

Triage: High

Arm Intervention Change Operation 34

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

Before

Arm 7

After

Part 1 Cohort 7

add /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/7

Triage: High

Arm Intervention Change Operation 35

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

After

Part 2 Cohort A

add /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/8

Triage: High

Arm Intervention Change Operation 36

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

After

Part 2 Cohort B

add /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/9

Triage: High

Arm Intervention Change Operation 37

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

After

Part 2 Cohort C

add /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/10

Triage: High

Arm Intervention Change Operation 38

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

After

Part 2 Cohort D

add /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/11

Triage: High

Arm Intervention Change Operation 39

Matched rules

arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure.

After

Part 2 Cohort E

Eligibility Criteria and population definition changes. Triage: High 1 ops

replace /protocolSection/eligibilityModule/eligibilityCriteria

Triage: High

Eligibility Change Operation 48

Matched rules

eligibility_criteria_change Eligibility criteria changes can alter the studied population.

Before

<p>Inclusion Criteria:</p><ul><li>Locally advanced, unresectable, or metastatic disease based on most recent imaging.</li><li><p>The respective cohorts for patient inclusion are:</p><ul><li>Cohort 1: Biliary tract cancer</li><li>Cohort 2: Bladder cancer</li><li>Cohort 3: Cervical cancer</li><li>Cohort 4: Endometrial cancer</li><li>Cohort 5: Epithelial ovarian cancer</li><li>Cohort 6: Pancreatic cancer</li><li>Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer.</li></ul></li><li>Progressed following prior treatment or who have no satisfactory alternative treatment option.</li><li>Prior HER2 targeting therapy is permitted.</li><li>HER2 expression for eligibility may be based on local or central assessment.</li><li>Has measurable target disease assessed by the Investigator based on RECIST version 1.1.</li><li>Has protocol- defined adequate organ function including cardiac, renal and hepatic function.</li></ul><p>Exclusion Criteria:</p><ul><li>History of non-infectious pneumonitis&#x2F;ILD that required steroids, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening</li><li>Lung-specific intercurrent clinically significant severe illnesses</li><li>Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals</li><li>Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART</li><li>Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression.</li><li>Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer.</li><li>Medical conditions that may interfere with the subject&#x27;s participation in the study.</li></ul>

After

<p>Inclusion Criteria:</p><ul><li>Locally advanced, unresectable, or metastatic disease based on most recent imaging.</li><li><p>Part 1:The respective cohorts for patient inclusion are:</p><ul><li>Cohort 1: Biliary tract cancer</li><li>Cohort 2: Bladder cancer</li><li>Cohort 3: Cervical cancer</li><li>Cohort 4: Endometrial cancer</li><li>Cohort 5: Epithelial ovarian cancer</li><li>Cohort 6: Pancreatic cancer</li><li>Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer.</li></ul></li><li><p>Part 2:The respective cohorts for patient inclusion are:</p><ul><li>Cohort A: Metastatic or advanced solid tumors that are HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer).
Patients with non-small cell lung cancer can be included.</li><li>Cohort B: Metastatic or advanced solid tumors that are HER2 IHC 2+&#x2F;ISH+ any tumor type (excluding breast, gastric cancer, and colorectal cancer).
Patients with non-small cell lung cancer can be included.</li><li>Cohort C: Metastatic or advanced solid endometrial cancer that is HER2 IHC 2+ or 1+.</li><li>Cohort D: Metastatic or advanced ovarian cancer that is HER2 IHC 2+ or 1+.</li><li>Cohort E: Metastatic or advanced solid cervical cancer that is HER2 IHC 2+ or 1+.</li></ul></li><li>Progressed following prior treatment or who have no satisfactory alternative treatment option.</li><li>Prior HER2 targeting therapy is permitted.</li><li><p>HER2 expression scored using current ASCO&#x2F;CAP guidelines for scoring HER2 for gastric cancer.</p><ul><li>Part 1: IHC 3+ or IHC 2+ by local or central assessment</li><li>Part 2: IHC and ISH results by central assessment as pre-defined for each cohort</li></ul></li><li>Has measurable target disease assessed by the Investigator based on RECIST version 1.1.</li><li>Has protocol- defined adequate organ function including cardiac, renal and hepatic function.</li></ul><p>Exclusion Criteria:</p><ul><li>History of non-infectious pneumonitis&#x2F;ILD that required steroids, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening</li><li>Lung-specific intercurrent clinically significant severe illnesses</li><li>Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals</li><li>Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART</li><li>Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression.</li><li>Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer for Part 1.
For Part 2, patients with primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction will be excluded.</li><li>Medical conditions that may interfere with the subject&#x27;s participation in the study.</li></ul>

Secondary outcomes Additional endpoints and outcome descriptions. Triage: High 7 ops

replace /protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame

Triage: High

Secondary Outcome Change Operation 41

Matched rules

secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.

Before

An average of approximately 41 months

After

An average of approximately 6 months

replace /protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame

Triage: High

Secondary Outcome Change Operation 42

Matched rules

secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.

Before

An average of approximately 41 months

After

An average of approximately 6 months

replace /protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame

Triage: High

Secondary Outcome Change Operation 43

Matched rules

secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.

Before

An average of approximately 41 months

After

An average of approximately 6 months

replace /protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame

Triage: High

Secondary Outcome Change Operation 44

Matched rules

secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.

Before

An average of approximately 41 months

After

An average of approximately 14 months

replace /protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame

Triage: High

Secondary Outcome Change Operation 45

Matched rules

secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.

Before

An average of approximately 41 months

After

An average of approximately 8 months

replace /protocolSection/outcomesModule/secondaryOutcomes/7/timeFrame

Triage: High

Secondary Outcome Change Operation 46

Matched rules

secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.

Before

An average of approximately 41 months

After

An average of approximately 8 months

replace /protocolSection/outcomesModule/secondaryOutcomes/8/timeFrame

Triage: High

Secondary Outcome Change Operation 47

Matched rules

secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.

Before

An average of approximately 41 months

After

An average of approximately 6 months

Timeline Start, primary completion, and completion date movement. Triage: Medium 1 ops

replace /protocolSection/statusModule/completionDateStruct/date

Triage: Medium

Timeline Shift Operation 2

Matched rules

completion_timeline_change Completion date changes are operational timeline signals.

Before

2027-03-31

After

2027-07-30

Contacts and locations Site, contact, and location updates that are usually operational. Triage: Uncategorized 8 ops

remove /protocolSection/contactsLocationsModule/locations/6

Triage: Uncategorized

Uncategorized Operation 49

Before

{
  "zip": "11725",
  "city": "Commack",
  "state": "New York",
  "country": "United States",
  "facility": "Research Site",
  "geoPoint": {
    "lat": 40.84288,
    "lon": -73.29289
  }
}

add /protocolSection/contactsLocationsModule/locations/8

Triage: Uncategorized

Uncategorized Operation 50

After

{
  "zip": "10065",
  "city": "New York",
  "state": "New York",
  "country": "United States",
  "facility": "Research Site",
  "geoPoint": {
    "lat": 40.71427,
    "lon": -74.00597
  }
}

replace /protocolSection/contactsLocationsModule/locations/11/zip

Triage: Uncategorized

Uncategorized Operation 51

Before

After

replace /protocolSection/contactsLocationsModule/locations/23/zip

Triage: Uncategorized

Uncategorized Operation 52

Before

775 20

After

remove /protocolSection/contactsLocationsModule/locations/32

Triage: Uncategorized

Uncategorized Operation 53

Before

{
  "zip": "00128",
  "city": "Roma",
  "country": "Italy",
  "facility": "Research Site",
  "geoPoint": {
    "lat": 44.99364,
    "lon": 11.10642
  }
}

replace /protocolSection/contactsLocationsModule/locations/38/zip

Triage: Uncategorized

Uncategorized Operation 54

Before

30-688

After

31-501

add /protocolSection/contactsLocationsModule/locations/52

Triage: Uncategorized

Uncategorized Operation 55

After

{
  "zip": "06351",
  "city": "Seoul",
  "country": "South Korea",
  "facility": "Research Site",
  "geoPoint": {
    "lat": 37.566,
    "lon": 126.9784
  }
}

remove /protocolSection/contactsLocationsModule/locations/54

Triage: Uncategorized

Uncategorized Operation 56

Before

{
  "zip": "6351",
  "city": "Seoul",
  "country": "South Korea",
  "facility": "Research Site",
  "geoPoint": {
    "lat": 37.566,
    "lon": 126.9784
  }
}

Other registry fields Changes outside the current high-signal rule families. Triage: Uncategorized 6 ops

replace /protocolSection/statusModule/statusVerifiedDate

Triage: Uncategorized

Uncategorized Operation 1

Before

2023-07

After

2024-01

replace /protocolSection/statusModule/lastUpdateSubmitDate

Triage: Uncategorized

Uncategorized Operation 3

Before

2023-07-07

After

2024-02-05

replace /protocolSection/statusModule/lastUpdatePostDateStruct/date

Triage: Uncategorized

Uncategorized Operation 4

Before

2023-07-10

After

2024-02-06

replace /protocolSection/descriptionModule/briefSummary

Triage: Uncategorized

Uncategorized Operation 5

Before

<p>This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors.</p><p>This study will enroll 7 cohorts: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors.</p><p>Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.</p>

After

<p>This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors.</p><p>This study will consist of Part 1 which includes 7 cohorts of: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors; and Part 2 which includes 5 cohorts A to E of: A) any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer), B) any tumor type that is HER2 IHC 2+&#x2F;ISH+ (excluding breast, gastric cancer, and colorectal cancer), C) HER2 IHC 2+ or 1+ endometrial cancer, D) HER2 IHC 2+ or 1+ ovarian cancer, and E) HER2 IHC 2+ or 1+ cervical cancer.</p><p>Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.</p>

replace /protocolSection/conditionsModule/conditions/0

Triage: Uncategorized

Uncategorized Operation 6

Before

Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Rare Tumors

After

Part 1: Bladder, Biliary Tract, Cervical, Endometrial, Ovarian, Pancreatic Cancer, Rare Tumors, Any Tumor Type Excluding Breast, Gastric, Colorectal Cancer

add /protocolSection/conditionsModule/conditions/1

Triage: Uncategorized

Uncategorized Operation 7

After

Part 2: HER2 Expressing&#x2F;Amplified Solid Tumors Excluding Breast, Gastric, Colorectal Cancer

Raw JSON Patch

[
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/statusVerifiedDate",
    "value": "2024-01"
  },
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/completionDateStruct/date",
    "value": "2027-07-30"
  },
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/lastUpdateSubmitDate",
    "value": "2024-02-05"
  },
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
    "value": "2024-02-06"
  },
  {
    "op": "replace",
    "path": "/protocolSection/descriptionModule/briefSummary",
    "value": "<p>This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors.</p><p>This study will consist of Part 1 which includes 7 cohorts of: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors; and Part 2 which includes 5 cohorts A to E of: A) any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer), B) any tumor type that is HER2 IHC 2+&#x2F;ISH+ (excluding breast, gastric cancer, and colorectal cancer), C) HER2 IHC 2+ or 1+ endometrial cancer, D) HER2 IHC 2+ or 1+ ovarian cancer, and E) HER2 IHC 2+ or 1+ cervical cancer.</p><p>Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.</p>"
  },
  {
    "op": "replace",
    "path": "/protocolSection/conditionsModule/conditions/0",
    "value": "Part 1: Bladder, Biliary Tract, Cervical, Endometrial, Ovarian, Pancreatic Cancer, Rare Tumors, Any Tumor Type Excluding Breast, Gastric, Colorectal Cancer"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/conditions/1",
    "value": "Part 2: HER2 Expressing&#x2F;Amplified Solid Tumors Excluding Breast, Gastric, Colorectal Cancer"
  },
  {
    "op": "replace",
    "path": "/protocolSection/designModule/designInfo/interventionModelDescription",
    "value": "This study will consist of Part 1 which includes 7 cohorts of: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors; and Part 2 which includes 5 cohorts A to E of: A) any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer), B) any tumor type that is HER2 IHC 2+&#x2F;ISH+ (excluding breast, gastric cancer, and colorectal cancer), C) HER2 IHC 2+ or 1+ endometrial cancer, D) HER2 IHC 2+ or 1+ ovarian cancer, and E) HER2 IHC 2+ or 1+ cervical cancer."
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/0/label",
    "value": "Part 1 Cohort 1"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/0/description",
    "value": "Biliary tract cancer"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/1/label",
    "value": "Part 1 Cohort 2"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/1/description",
    "value": "Bladder cancer"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/2/label",
    "value": "Part 1 Cohort 3"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/2/description",
    "value": "Cervical cancer"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/3/label",
    "value": "Part 1 Cohort 4"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/3/description",
    "value": "Endometrial cancer"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/4/label",
    "value": "Part 1 Cohort 5"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/4/description",
    "value": "Ovarian cancer"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/5/label",
    "value": "Part 1 Cohort 6"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/5/description",
    "value": "Pancreatic cancer"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/6/label",
    "value": "Part 1 Cohort 7"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/armGroups/6/description",
    "value": "Rare tumors"
  },
  {
    "op": "add",
    "path": "/protocolSection/armsInterventionsModule/armGroups/7",
    "value": {
      "type": "EXPERIMENTAL",
      "label": "Part 2 Cohort A",
      "description": "Any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer)",
      "interventionNames": [
        "Drug: Trastuzumab deruxtecan"
      ]
    }
  },
  {
    "op": "add",
    "path": "/protocolSection/armsInterventionsModule/armGroups/8",
    "value": {
      "type": "EXPERIMENTAL",
      "label": "Part 2 Cohort B",
      "description": "Any tumor type that is HER2 IHC 2+&#x2F;ISH+ (excluding breast, gastric cancer, and colorectal cancer)",
      "interventionNames": [
        "Drug: Trastuzumab deruxtecan"
      ]
    }
  },
  {
    "op": "add",
    "path": "/protocolSection/armsInterventionsModule/armGroups/9",
    "value": {
      "type": "EXPERIMENTAL",
      "label": "Part 2 Cohort C",
      "description": "HER2 IHC 2+ or 1+ endometrial cancer",
      "interventionNames": [
        "Drug: Trastuzumab deruxtecan"
      ]
    }
  },
  {
    "op": "add",
    "path": "/protocolSection/armsInterventionsModule/armGroups/10",
    "value": {
      "type": "EXPERIMENTAL",
      "label": "Part 2 Cohort D",
      "description": "HER2 IHC 2+ or 1+ ovarian cancer",
      "interventionNames": [
        "Drug: Trastuzumab deruxtecan"
      ]
    }
  },
  {
    "op": "add",
    "path": "/protocolSection/armsInterventionsModule/armGroups/11",
    "value": {
      "type": "EXPERIMENTAL",
      "label": "Part 2 Cohort E",
      "description": "HER2 IHC 2+ or 1+ cervical cancer",
      "interventionNames": [
        "Drug: Trastuzumab deruxtecan"
      ]
    }
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/0",
    "value": "Part 1 Cohort 1"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/1",
    "value": "Part 1 Cohort 2"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/2",
    "value": "Part 1 Cohort 3"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/3",
    "value": "Part 1 Cohort 4"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/4",
    "value": "Part 1 Cohort 5"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/5",
    "value": "Part 1 Cohort 6"
  },
  {
    "op": "replace",
    "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/6",
    "value": "Part 1 Cohort 7"
  },
  {
    "op": "add",
    "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/7",
    "value": "Part 2 Cohort A"
  },
  {
    "op": "add",
    "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/8",
    "value": "Part 2 Cohort B"
  },
  {
    "op": "add",
    "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/9",
    "value": "Part 2 Cohort C"
  },
  {
    "op": "add",
    "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/10",
    "value": "Part 2 Cohort D"
  },
  {
    "op": "add",
    "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/11",
    "value": "Part 2 Cohort E"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
    "value": "An average of approximately 6 months"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame",
    "value": "An average of approximately 6 months"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
    "value": "An average of approximately 6 months"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
    "value": "An average of approximately 6 months"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame",
    "value": "An average of approximately 14 months"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame",
    "value": "An average of approximately 8 months"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/7/timeFrame",
    "value": "An average of approximately 8 months"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/8/timeFrame",
    "value": "An average of approximately 6 months"
  },
  {
    "op": "replace",
    "path": "/protocolSection/eligibilityModule/eligibilityCriteria",
    "value": "<p>Inclusion Criteria:</p><ul><li>Locally advanced, unresectable, or metastatic disease based on most recent imaging.</li><li><p>Part 1:The respective cohorts for patient inclusion are:</p><ul><li>Cohort 1: Biliary tract cancer</li><li>Cohort 2: Bladder cancer</li><li>Cohort 3: Cervical cancer</li><li>Cohort 4: Endometrial cancer</li><li>Cohort 5: Epithelial ovarian cancer</li><li>Cohort 6: Pancreatic cancer</li><li>Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer.</li></ul></li><li><p>Part 2:The respective cohorts for patient inclusion are:</p><ul><li>Cohort A: Metastatic or advanced solid tumors that are HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer).\nPatients with non-small cell lung cancer can be included.</li><li>Cohort B: Metastatic or advanced solid tumors that are HER2 IHC 2+&#x2F;ISH+ any tumor type (excluding breast, gastric cancer, and colorectal cancer).\nPatients with non-small cell lung cancer can be included.</li><li>Cohort C: Metastatic or advanced solid endometrial cancer that is HER2 IHC 2+ or 1+.</li><li>Cohort D: Metastatic or advanced ovarian cancer that is HER2 IHC 2+ or 1+.</li><li>Cohort E: Metastatic or advanced solid cervical cancer that is HER2 IHC 2+ or 1+.</li></ul></li><li>Progressed following prior treatment or who have no satisfactory alternative treatment option.</li><li>Prior HER2 targeting therapy is permitted.</li><li><p>HER2 expression scored using current ASCO&#x2F;CAP guidelines for scoring HER2 for gastric cancer.</p><ul><li>Part 1: IHC 3+ or IHC 2+ by local or central assessment</li><li>Part 2: IHC and ISH results by central assessment as pre-defined for each cohort</li></ul></li><li>Has measurable target disease assessed by the Investigator based on RECIST version 1.1.</li><li>Has protocol- defined adequate organ function including cardiac, renal and hepatic function.</li></ul><p>Exclusion Criteria:</p><ul><li>History of non-infectious pneumonitis&#x2F;ILD that required steroids, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening</li><li>Lung-specific intercurrent clinically significant severe illnesses</li><li>Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals</li><li>Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART</li><li>Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression.</li><li>Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer for Part 1.\nFor Part 2, patients with primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction will be excluded.</li><li>Medical conditions that may interfere with the subject&#x27;s participation in the study.</li></ul>"
  },
  {
    "op": "remove",
    "path": "/protocolSection/contactsLocationsModule/locations/6"
  },
  {
    "op": "add",
    "path": "/protocolSection/contactsLocationsModule/locations/8",
    "value": {
      "zip": "10065",
      "city": "New York",
      "state": "New York",
      "country": "United States",
      "facility": "Research Site",
      "geoPoint": {
        "lat": 40.71427,
        "lon": -74.00597
      }
    }
  },
  {
    "op": "replace",
    "path": "/protocolSection/contactsLocationsModule/locations/11/zip",
    "value": "98195"
  },
  {
    "op": "replace",
    "path": "/protocolSection/contactsLocationsModule/locations/23/zip",
    "value": "77900"
  },
  {
    "op": "remove",
    "path": "/protocolSection/contactsLocationsModule/locations/32"
  },
  {
    "op": "replace",
    "path": "/protocolSection/contactsLocationsModule/locations/38/zip",
    "value": "31-501"
  },
  {
    "op": "add",
    "path": "/protocolSection/contactsLocationsModule/locations/52",
    "value": {
      "zip": "06351",
      "city": "Seoul",
      "country": "South Korea",
      "facility": "Research Site",
      "geoPoint": {
        "lat": 37.566,
        "lon": 126.9784
      }
    }
  },
  {
    "op": "remove",
    "path": "/protocolSection/contactsLocationsModule/locations/54"
  }
]