Evidence Record
evt_NCT04224272_v16_v17_b0a08c4f6b0a
NCT04224272 · A Study of ZW25 (Zanidatamab) With Palbociclib Plus Fulvestrant in Patients With HER2+/HR+ Advanced Breast Cancer
Severity is deterministic, reproducible, uncalibrated triage metadata, not validated review priority or proven wrongdoing. This page states what the registry evidence supports and what it does not support.
Triage severity
Triage: Low Category
Results Reconciliation
Versions
v16 to v17
Timing
Late Recruitment
Claims Supported
- TrialDiff compared ClinicalTrials.gov record version 16 to version 17 for NCT04224272.
- The JSON Patch for this comparison has hash a8c71eea396a25024fa25c27f7889f2205fdc6331fd436f4257d3ee232ac477f.
- The active deterministic rule set hash was fc87f4f0a74bc789dbe4ba85893c2c96f55db62c22970be4e991288104291621.
- The deterministic triage label was low; before timing adjustment it was low.
- The triage label is uncalibrated metadata, not a validated review-priority finding.
- The patch satisfied these deterministic event-class predicates: outcome_edit_cooccurs_with_results_posting.
- The timing context for the from-version record was late_recruitment.
- The changed JSON Pointer paths were: /protocolSection/statusModule/statusVerifiedDate, /protocolSection/statusModule/lastUpdateSubmitDate, /protocolSection/statusModule/lastUpdatePostDateStruct/date, /protocolSection/statusModule/resultsFirstSubmitDate, /protocolSection/outcomesModule/primaryOutcomes/0/measure, /protocolSection/outcomesModule/primaryOutcomes/0/description, /protocolSection/outcomesModule/primaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/primaryOutcomes/1/measure, /protocolSection/outcomesModule/primaryOutcomes/1/description, /protocolSection/outcomesModule/primaryOutcomes/1/timeFrame, /protocolSection/outcomesModule/primaryOutcomes/2/measure, /protocolSection/outcomesModule/primaryOutcomes/2/description, /protocolSection/outcomesModule/primaryOutcomes/2/timeFrame, /protocolSection/outcomesModule/primaryOutcomes/2/reviewUnit, /protocolSection/outcomesModule/primaryOutcomes/3, /protocolSection/outcomesModule/secondaryOutcomes/0/measure, /protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/0/description, /protocolSection/outcomesModule/secondaryOutcomes/1/measure, /protocolSection/outcomesModule/secondaryOutcomes/1/description, /protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/2/measure, /protocolSection/outcomesModule/secondaryOutcomes/2/description, /protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/3/measure, /protocolSection/outcomesModule/secondaryOutcomes/3/description, /protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/4/measure, /protocolSection/outcomesModule/secondaryOutcomes/4/description, /protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/5/measure, /protocolSection/outcomesModule/secondaryOutcomes/5/description, /protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/6/measure, /protocolSection/outcomesModule/secondaryOutcomes/6/description, /protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/7/measure, /protocolSection/outcomesModule/secondaryOutcomes/7/description, /protocolSection/outcomesModule/secondaryOutcomes/7/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/8/measure, /protocolSection/outcomesModule/secondaryOutcomes/8/description, /protocolSection/outcomesModule/secondaryOutcomes/8/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/9/measure, /protocolSection/outcomesModule/secondaryOutcomes/9/description, /protocolSection/outcomesModule/secondaryOutcomes/9/timeFrame, /hasResults, /resultsSection, /annotationSection, /documentSection.
- An outcome path changed between versions 16 and 17 in a patch that also carried a hasResults or resultsSection co-occurrence signal.
Claims Not Supported
- That the amendment was scientifically unjustified.
- That the change constitutes misconduct or wrongdoing.
- That sponsor intent can be inferred from this registry change.
- That the change caused or altered the trial's results.
- That the change was or was not disclosed in a manuscript.
- That TrialDiff determines regulatory compliance or non-compliance.
- That co-occurrence with results posting proves the outcome edit was harmless, administrative, or substantively benign.
- That event-class membership is a validated global review-priority ranking.
Neutral Review Question
What source document explains this registry amendment, and does it change interpretation of the trial record?
Citation
TrialDiff Evidence Record evt_NCT04224272_v16_v17_b0a08c4f6b0a. ClinicalTrials.gov NCT04224272, versions 16-17. Evidence version 1.
Event Classes
outcome_edit_cooccurs_with_results_posting Changed Paths
/protocolSection/statusModule/statusVerifiedDate
/protocolSection/statusModule/lastUpdateSubmitDate
/protocolSection/statusModule/lastUpdatePostDateStruct/date
/protocolSection/statusModule/resultsFirstSubmitDate
/protocolSection/outcomesModule/primaryOutcomes/0/measure
/protocolSection/outcomesModule/primaryOutcomes/0/description
/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame
/protocolSection/outcomesModule/primaryOutcomes/1/measure
/protocolSection/outcomesModule/primaryOutcomes/1/description
/protocolSection/outcomesModule/primaryOutcomes/1/timeFrame
/protocolSection/outcomesModule/primaryOutcomes/2/measure
/protocolSection/outcomesModule/primaryOutcomes/2/description
/protocolSection/outcomesModule/primaryOutcomes/2/timeFrame
/protocolSection/outcomesModule/primaryOutcomes/2/reviewUnit
/protocolSection/outcomesModule/primaryOutcomes/3
/protocolSection/outcomesModule/secondaryOutcomes/0/measure
/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/0/description
/protocolSection/outcomesModule/secondaryOutcomes/1/measure
/protocolSection/outcomesModule/secondaryOutcomes/1/description
/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/2/measure
/protocolSection/outcomesModule/secondaryOutcomes/2/description
/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/3/measure
/protocolSection/outcomesModule/secondaryOutcomes/3/description
/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/4/measure
/protocolSection/outcomesModule/secondaryOutcomes/4/description
/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/5/measure
/protocolSection/outcomesModule/secondaryOutcomes/5/description
/protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/6/measure
/protocolSection/outcomesModule/secondaryOutcomes/6/description
/protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/7/measure
/protocolSection/outcomesModule/secondaryOutcomes/7/description
/protocolSection/outcomesModule/secondaryOutcomes/7/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/8/measure
/protocolSection/outcomesModule/secondaryOutcomes/8/description
/protocolSection/outcomesModule/secondaryOutcomes/8/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/9/measure
/protocolSection/outcomesModule/secondaryOutcomes/9/description
/protocolSection/outcomesModule/secondaryOutcomes/9/timeFrame
/hasResults
/resultsSection
/annotationSection
/documentSection
View the field-level diff for before/after values on each changed path.
Deterministic Rules
No deterministic rules recorded.
Provenance
- Package generation
v0.1.3(active)- Supersedes
- evt_NCT04224272_v16_v17_6b94b2e4bfd9
- Patch hash
a8c71eea396a25024fa25c27f7889f2205fdc6331fd436f4257d3ee232ac477f- Canonical hash
845e157415908a554f737106ad0047829b1097821f8e6642c6c9059890c49248- Rule set hash
fc87f4f0a74bc789dbe4ba85893c2c96f55db62c22970be4e991288104291621- From snapshot
1eb69556ed6a452369e37075ff2f3161a172836d59c796ae0a6ab53d0b5ca54d- To snapshot
0a05389475c64483d67a86b9f1c4b0fc058b0014a8f94ddff08ba22edacf89d1- Patch source
- ctgov_internal_history
- Generated at
- 2026-08-03T06:46:43.000Z
- Source URL
- Registry payload
Canonical JSON Preview
Stored payload{
"changed_paths": [
"/protocolSection/statusModule/statusVerifiedDate",
"/protocolSection/statusModule/lastUpdateSubmitDate",
"/protocolSection/statusModule/lastUpdatePostDateStruct/date",
"/protocolSection/statusModule/resultsFirstSubmitDate",
"/protocolSection/outcomesModule/primaryOutcomes/0/measure",
"/protocolSection/outcomesModule/primaryOutcomes/0/description",
"/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
"/protocolSection/outcomesModule/primaryOutcomes/1/measure",
"/protocolSection/outcomesModule/primaryOutcomes/1/description",
"/protocolSection/outcomesModule/primaryOutcomes/1/timeFrame",
"/protocolSection/outcomesModule/primaryOutcomes/2/measure",
"/protocolSection/outcomesModule/primaryOutcomes/2/description",
"/protocolSection/outcomesModule/primaryOutcomes/2/timeFrame",
"/protocolSection/outcomesModule/primaryOutcomes/2/reviewUnit",
"/protocolSection/outcomesModule/primaryOutcomes/3",
"/protocolSection/outcomesModule/secondaryOutcomes/0/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/0/description",
"/protocolSection/outcomesModule/secondaryOutcomes/1/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/1/description",
"/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/2/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/2/description",
"/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/3/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/3/description",
"/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/4/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/4/description",
"/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/5/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/5/description",
"/protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/6/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/6/description",
"/protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/7/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/7/description",
"/protocolSection/outcomesModule/secondaryOutcomes/7/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/8/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/8/description",
"/protocolSection/outcomesModule/secondaryOutcomes/8/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/9/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/9/description",
"/protocolSection/outcomesModule/secondaryOutcomes/9/timeFrame",
"/hasResults",
"/resultsSection",
"/annotationSection",
"/documentSection"
],
"citation_text": "TrialDiff Evidence Record evt_NCT04224272_v16_v17_b0a08c4f6b0a. ClinicalTrials.gov NCT04224272, versions 16-17. Evidence version 1.",
"claims_not_supported": [
"That the amendment was scientifically unjustified.",
"That the change constitutes misconduct or wrongdoing.",
"That sponsor intent can be inferred from this registry change.",
"That the change caused or altered the trial's results.",
"That the change was or was not disclosed in a manuscript.",
"That TrialDiff determines regulatory compliance or non-compliance.",
"That co-occurrence with results posting proves the outcome edit was harmless, administrative, or substantively benign.",
"That event-class membership is a validated global review-priority ranking."
],
"claims_supported": [
"TrialDiff compared ClinicalTrials.gov record version 16 to version 17 for NCT04224272.",
"The JSON Patch for this comparison has hash a8c71eea396a25024fa25c27f7889f2205fdc6331fd436f4257d3ee232ac477f.",
"The active deterministic rule set hash was fc87f4f0a74bc789dbe4ba85893c2c96f55db62c22970be4e991288104291621.",
"The deterministic triage label was low; before timing adjustment it was low.",
"The triage label is uncalibrated metadata, not a validated review-priority finding.",
"The patch satisfied these deterministic event-class predicates: outcome_edit_cooccurs_with_results_posting.",
"The timing context for the from-version record was late_recruitment.",
"The changed JSON Pointer paths were: /protocolSection/statusModule/statusVerifiedDate, /protocolSection/statusModule/lastUpdateSubmitDate, /protocolSection/statusModule/lastUpdatePostDateStruct/date, /protocolSection/statusModule/resultsFirstSubmitDate, /protocolSection/outcomesModule/primaryOutcomes/0/measure, /protocolSection/outcomesModule/primaryOutcomes/0/description, /protocolSection/outcomesModule/primaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/primaryOutcomes/1/measure, /protocolSection/outcomesModule/primaryOutcomes/1/description, /protocolSection/outcomesModule/primaryOutcomes/1/timeFrame, /protocolSection/outcomesModule/primaryOutcomes/2/measure, /protocolSection/outcomesModule/primaryOutcomes/2/description, /protocolSection/outcomesModule/primaryOutcomes/2/timeFrame, /protocolSection/outcomesModule/primaryOutcomes/2/reviewUnit, /protocolSection/outcomesModule/primaryOutcomes/3, /protocolSection/outcomesModule/secondaryOutcomes/0/measure, /protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/0/description, /protocolSection/outcomesModule/secondaryOutcomes/1/measure, /protocolSection/outcomesModule/secondaryOutcomes/1/description, /protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/2/measure, /protocolSection/outcomesModule/secondaryOutcomes/2/description, /protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/3/measure, /protocolSection/outcomesModule/secondaryOutcomes/3/description, /protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/4/measure, /protocolSection/outcomesModule/secondaryOutcomes/4/description, /protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/5/measure, /protocolSection/outcomesModule/secondaryOutcomes/5/description, /protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/6/measure, /protocolSection/outcomesModule/secondaryOutcomes/6/description, /protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/7/measure, /protocolSection/outcomesModule/secondaryOutcomes/7/description, /protocolSection/outcomesModule/secondaryOutcomes/7/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/8/measure, /protocolSection/outcomesModule/secondaryOutcomes/8/description, /protocolSection/outcomesModule/secondaryOutcomes/8/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/9/measure, /protocolSection/outcomesModule/secondaryOutcomes/9/description, /protocolSection/outcomesModule/secondaryOutcomes/9/timeFrame, /hasResults, /resultsSection, /annotationSection, /documentSection.",
"An outcome path changed between versions 16 and 17 in a patch that also carried a hasResults or resultsSection co-occurrence signal."
],
"classification": {
"calibration_status": "uncalibrated",
"categories": [
"results_reconciliation"
],
"category": "results_reconciliation",
"deterministic_rules": [],
"event_class_rule_set_hash": "74a6f55a686c29aa023171acd6b43f27ea95f2b0af2d49094ac70287ba4e502c",
"event_classes": [
"outcome_edit_cooccurs_with_results_posting"
],
"rule_set_hash": "fc87f4f0a74bc789dbe4ba85893c2c96f55db62c22970be4e991288104291621",
"severity": "low",
"severity_pre_timing": "low",
"timing_context": "late_recruitment",
"triage_label": "low",
"triage_rule_set_hash": "af5e5835e00a5fcfe2a17fd02b5fc244c2564104f93f78a1d77d7889f12a178b",
"value_signals": [
{
"category": "results_reconciliation",
"paths": [
"/protocolSection/outcomesModule/primaryOutcomes/0/description",
"/protocolSection/outcomesModule/primaryOutcomes/0/measure",
"/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
"/protocolSection/outcomesModule/primaryOutcomes/1/description",
"/protocolSection/outcomesModule/primaryOutcomes/1/measure",
"/protocolSection/outcomesModule/primaryOutcomes/1/timeFrame",
"/protocolSection/outcomesModule/primaryOutcomes/2/description",
"/protocolSection/outcomesModule/primaryOutcomes/2/measure",
"/protocolSection/outcomesModule/primaryOutcomes/2/reviewUnit",
"/protocolSection/outcomesModule/primaryOutcomes/2/timeFrame",
"/protocolSection/outcomesModule/primaryOutcomes/3",
"/protocolSection/outcomesModule/secondaryOutcomes/0/description",
"/protocolSection/outcomesModule/secondaryOutcomes/0/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/1/description",
"/protocolSection/outcomesModule/secondaryOutcomes/1/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/2/description",
"/protocolSection/outcomesModule/secondaryOutcomes/2/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/3/description",
"/protocolSection/outcomesModule/secondaryOutcomes/3/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/4/description",
"/protocolSection/outcomesModule/secondaryOutcomes/4/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/5/description",
"/protocolSection/outcomesModule/secondaryOutcomes/5/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/6/description",
"/protocolSection/outcomesModule/secondaryOutcomes/6/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/7/description",
"/protocolSection/outcomesModule/secondaryOutcomes/7/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/7/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/8/description",
"/protocolSection/outcomesModule/secondaryOutcomes/8/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/8/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/9/description",
"/protocolSection/outcomesModule/secondaryOutcomes/9/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/9/timeFrame"
],
"severity": "low",
"signal": "results_reconciliation_outcome_suppression"
}
]
},
"event_id": "evt_NCT04224272_v16_v17_b0a08c4f6b0a",
"evidence_version": 1,
"patch": [
{
"op": "replace",
"path": "/protocolSection/statusModule/statusVerifiedDate",
"value": "2024-04"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/lastUpdateSubmitDate",
"value": "2024-04-26"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
"value": "2024-05-24"
},
{
"op": "add",
"path": "/protocolSection/statusModule/resultsFirstSubmitDate",
"value": "2024-04-26"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
"value": "Number of Participants With Dose-Limiting Toxicities"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/0/description",
"value": "Dose-limiting toxicities, defined using NCI CTCAE version 5.0, are events that 1) occur following administration of ZW25, palbociclib, and fulvestrant, or any combination of ZW25 and 1 or more of these drugs; and 2) meet the criteria as specified in the protocol."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
"value": "Cycle 1 Day 1 to Day 28 (each cycle is 28 days)"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/1/measure",
"value": "Number of Participants Reporting Grade 3 or Higher Treatment-emergent Adverse Events"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/1/description",
"value": "A treatment-emergent adverse event occurs after the start of study treatment and is defined as any unfavorable or unintended symptom, sign, or disease (including abnormal lab) temporally associated with the use of treatment that may or may not be considered related to treatment.\nTEAEs were coded using MedDRA v24.0."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/1/timeFrame",
"value": "Baseline from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 2 years 10 months."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/2/measure",
"value": "Progression-free Survival 6"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/2/description",
"value": "Progression-free survival at 6 months (PFS6) is defined as having a progression-free survival time greater than or equal to 24 weeks at the time of analysis where PFS time is defined as the time from the first dose of ZW25, palbociclib, and/or fulvestrant to the date of documented disease progression (per RECIST 1.1) or death from any cause."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/2/timeFrame",
"value": "6 months from first dose of any study drug to the date of documented disease progression or death, up to approximately 2 years 10 months"
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/primaryOutcomes/2/reviewUnit",
"value": {
"resetReasons": [
"There does not appear to be sufficient information to understand the Time Frame."
]
}
},
{
"op": "remove",
"path": "/protocolSection/outcomesModule/primaryOutcomes/3"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/0/measure",
"value": "Number of Participants Reporting Any Treatment-emergent Adverse Event, Serious Adverse Event, and Adverse Event of Special Interest"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame",
"value": "From the start of dosing of any study drug up until 30 days after last study dose, up to approximately 2 years 10 months"
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/0/description",
"value": "A treatment-emergent adverse events (TEAEs) was defined as an adverse event (AE) with onset on or after 1st dose of study treatment through 30 days after final dose of study treatment inclusive.\nAn AE is classified as a serious adverse event (SAE) if fatal, life threatening, requires hospitalization, is disabling/incapacitating, causes congenital anomaly or birth defect, and medically significant.\nAdverse events of special interest (AESI) include absolute decreases in LVEF greater than or equal to 10 percentage points from baseline, symptomatic heart failure, infusion-related reactions, and all greater than or equal to Grade 2 events of pneumonitis and/or interstitial lung disease, including pulmonary fibrosis."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/1/measure",
"value": "Maximum Serum Concentration of ZW25"
},
{
"op": "remove",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/1/description"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
"value": "Cycle 1, Days 1, 2, 5, 15; Cycle 2, Days 1 and 15; Day 1 of all subsequent cycles (each cycle is 28 days); and end of treatment, up to approximately 5 years 4 months"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/2/measure",
"value": "Trough Concentration of ZW25"
},
{
"op": "remove",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/2/description"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
"value": "Cycle 1, Days 1, 2, 5, 15; Cycle 2, Days 1 and 15; Day 1 of all subsequent cycles (each cycle is 28 days); and end of treatment, up to approximately 5 years 4 months"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/3/measure",
"value": "Incidence of Anti-drug Antibodies (ADAs)"
},
{
"op": "remove",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/3/description"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
"value": "Cycles 1 and 2, Day 15; Day 1 of all subsequent cycles (each cycle is 28 days); end of treatment, 30 days post-last dose (safety follow up), and every 8 weeks (efficacy follow up), up to approximately 5 years 4 months"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/4/measure",
"value": "Objective Response Rate"
},
{
"op": "remove",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/4/description"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame",
"value": "Baseline up to end of study, approximately 5 years 4 months"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/5/measure",
"value": "Duration of Response"
},
{
"op": "remove",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/5/description"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame",
"value": "Baseline up to end of study, approximately 5 years 4 months"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/6/measure",
"value": "Disease Control Rate"
},
{
"op": "remove",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/6/description"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame",
"value": "Baseline up to end of study, approximately 5 years 4 months"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/7/measure",
"value": "Progression-free Survival"
},
{
"op": "remove",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/7/description"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/7/timeFrame",
"value": "Baseline up to end of study, approximately 5 years 4 months"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/8/measure",
"value": "Overall Survival"
},
{
"op": "remove",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/8/description"
},
{
"op": "replace",
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"type": "PRIMARY",
"unitOfMeasure": "Participants"
},
{
"classes": [
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "51"
}
]
}
],
"title": "TEAE"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "8"
}
]
}
],
"title": "SAE"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "10"
}
]
}
],
"title": "AESI"
}
],
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "51"
}
],
"units": "Participants"
}
],
"description": "A treatment-emergent adverse events (TEAEs) was defined as an adverse event (AE) with onset on or after 1st dose of study treatment through 30 days after final dose of study treatment inclusive.\nAn AE is classified as a serious adverse event (SAE) if fatal, life threatening, requires hospitalization, is disabling/incapacitating, causes congenital anomaly or birth defect, and medically significant.\nAdverse events of special interest (AESI) include absolute decreases in LVEF greater than or equal to 10 percentage points from baseline, symptomatic heart failure, infusion-related reactions, and all greater than or equal to Grade 2 events of pneumonitis and/or interstitial lung disease, including pulmonary fibrosis.",
"groups": [
{
"description": "Participants who received an intravenous dose of 20 mg/kg ZW25 (zanidatamab) every 2 weeks (Q2W) in combination with an oral administration of 125 mg palbociclib once daily from Days 1 to 21, and an intramuscular injection of 500 mg fulvestrant Q2W for 3 doses (Cycle 1 Days 1 and 15 and Cycle 2 Day 1), and every 4 weeks (Q4W) thereafter.",
"id": "OG000",
"title": "ZW25 (Zanidatamab) + Palbociclib + Fulvestrant"
}
],
"paramType": "COUNT_OF_PARTICIPANTS",
"populationDescription": "Safety data were assessed in the Safety Analysis Set.",
"reportingStatus": "POSTED",
"timeFrame": "From the start of dosing of any study drug up until 30 days after last study dose, up to approximately 2 years 10 months",
"title": "Number of Participants Reporting Any Treatment-emergent Adverse Event, Serious Adverse Event, and Adverse Event of Special Interest",
"type": "SECONDARY",
"unitOfMeasure": "Participants"
},
{
"classes": [
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "20"
}
]
}
],
"title": "Any Blood and Lymphatic System Disorders AE"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "16"
}
]
}
],
"title": "Neutropenia"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "6"
}
]
}
],
"title": "Anaemia"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "3"
}
]
}
],
"title": "Thrombocytopenia"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "13"
}
]
}
],
"title": "Any Gastrointestinal Disorder AE"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "8"
}
]
}
],
"title": "Diarrhoea"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Abdominal pain"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Duodenal ulcer"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Gastric ulcer"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Nausea"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Small intestinal obstruction"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Stomatitis"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Vomiting"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "12"
}
]
}
],
"title": "Any Investigation AE"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "11"
}
]
}
],
"title": "Neutrophil count decreased"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Ejection fraction decreased"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Transaminases increased"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "White blood cell count decreased"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "8"
}
]
}
],
"title": "Any Metabolism and Nutrition Disorder AE"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "4"
}
]
}
],
"title": "Hypokalaemia"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "3"
}
]
}
],
"title": "Hypomagnesaemia"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "2"
}
]
}
],
"title": "Hypercalcaemia"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "2"
}
]
}
],
"title": "Any General Disorders and Administration Site Conditions AE"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Fatigue"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Pyrexia"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "2"
}
]
}
],
"title": "Any Infections and Infestations AE"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "COVID-19 pneumonia"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Psoas abscess"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Staphylococcal bacteraemia"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "2"
}
]
}
],
"title": "Any Respiratory, Thoracic and Mediastinal Disorder AE"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Pleural effusion"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Pneumothorax"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Any Renal and Urinary Disorder AE"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Acute kidney injury"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Any Skin and Subcutaneous Tissue Disorder AE"
},
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "1"
}
]
}
],
"title": "Rash maculo-papular"
}
],
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "51"
}
],
"units": "Participants"
}
],
"description": "A treatment-emergent adverse event occurs after the start of study treatment and is defined as any unfavorable or unintended symptom, sign, or disease (including abnormal lab) temporally associated with the use of treatment that may or may not be considered related to treatment.\nTEAEs were coded using MedDRA v24.0.",
"groups": [
{
"description": "Participants who received an intravenous dose of 20 mg/kg ZW25 (zanidatamab) every 2 weeks (Q2W) in combination with an oral administration of 125 mg palbociclib once daily from Days 1 to 21, and an intramuscular injection of 500 mg fulvestrant Q2W for 3 doses (Cycle 1 Days 1 and 15 and Cycle 2 Day 1), and every 4 weeks (Q4W) thereafter.",
"id": "OG000",
"title": "ZW25 (Zanidatamab) + Palbociclib + Fulvestrant"
}
],
"paramType": "COUNT_OF_PARTICIPANTS",
"populationDescription": "Treatment-emergent adverse events were assessed in the Safety Analysis Set.",
"reportingStatus": "POSTED",
"timeFrame": "Baseline from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 2 years 10 months.",
"title": "Number of Participants Reporting Grade 3 or Higher Treatment-emergent Adverse Events",
"type": "PRIMARY",
"unitOfMeasure": "Participants"
},
{
"classes": [
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "34"
}
]
}
]
}
],
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "51"
}
],
"units": "Participants"
}
],
"description": "Progression-free survival at 6 months (PFS6) is defined as having a progression-free survival time greater than or equal to 24 weeks at the time of analysis where PFS time is defined as the time from the first dose of ZW25, palbociclib, and/or fulvestrant to the date of documented disease progression (per RECIST 1.1) or death from any cause.",
"groups": [
{
"description": "Participants who received an intravenous dose of 20 mg/kg ZW25 (zanidatamab) every 2 weeks (Q2W) in combination with an oral administration of 125 mg palbociclib once daily from Days 1 to 21, and an intramuscular injection of 500 mg fulvestrant Q2W for 3 doses (Cycle 1 Days 1 and 15 and Cycle 2 Day 1), and every 4 weeks (Q4W) thereafter.",
"id": "OG000",
"title": "ZW25 (Zanidatamab) + Palbociclib + Fulvestrant"
}
],
"paramType": "COUNT_OF_PARTICIPANTS",
"populationDescription": "Progression-free survival 6 will be assessed in the Safety Analysis Set.",
"reportingStatus": "POSTED",
"reviewUnit": {
"resetReasons": [
"There does not appear to be sufficient information to understand the Time Frame."
]
},
"timeFrame": "6 months from first dose of any study drug to the date of documented disease progression or death, up to approximately 2 years 10 months",
"title": "Progression-free Survival 6",
"type": "PRIMARY",
"unitOfMeasure": "Participants"
},
{
"anticipatedPostingDate": "2026-10",
"denomUnitsSelected": "Participants",
"reportingStatus": "NOT_POSTED",
"timeFrame": "Cycle 1, Days 1, 2, 5, 15; Cycle 2, Days 1 and 15; Day 1 of all subsequent cycles (each cycle is 28 days); and end of treatment, up to approximately 5 years 4 months",
"title": "Maximum Serum Concentration of ZW25",
"type": "SECONDARY"
},
{
"anticipatedPostingDate": "2026-10",
"denomUnitsSelected": "Participants",
"reportingStatus": "NOT_POSTED",
"timeFrame": "Cycle 1, Days 1, 2, 5, 15; Cycle 2, Days 1 and 15; Day 1 of all subsequent cycles (each cycle is 28 days); and end of treatment, up to approximately 5 years 4 months",
"title": "Trough Concentration of ZW25",
"type": "SECONDARY"
},
{
"anticipatedPostingDate": "2026-10",
"denomUnitsSelected": "Participants",
"reportingStatus": "NOT_POSTED",
"timeFrame": "Cycles 1 and 2, Day 15; Day 1 of all subsequent cycles (each cycle is 28 days); end of treatment, 30 days post-last dose (safety follow up), and every 8 weeks (efficacy follow up), up to approximately 5 years 4 months",
"title": "Incidence of Anti-drug Antibodies (ADAs)",
"type": "SECONDARY"
},
{
"anticipatedPostingDate": "2026-10",
"denomUnitsSelected": "Participants",
"reportingStatus": "NOT_POSTED",
"timeFrame": "Baseline up to end of study, approximately 5 years 4 months",
"title": "Objective Response Rate",
"type": "SECONDARY"
},
{
"anticipatedPostingDate": "2026-10",
"denomUnitsSelected": "Participants",
"reportingStatus": "NOT_POSTED",
"timeFrame": "Baseline up to end of study, approximately 5 years 4 months",
"title": "Duration of Response",
"type": "SECONDARY"
},
{
"anticipatedPostingDate": "2026-10",
"denomUnitsSelected": "Participants",
"reportingStatus": "NOT_POSTED",
"timeFrame": "Baseline up to end of study, approximately 5 years 4 months",
"title": "Disease Control Rate",
"type": "SECONDARY"
},
{
"anticipatedPostingDate": "2026-10",
"denomUnitsSelected": "Participants",
"reportingStatus": "NOT_POSTED",
"timeFrame": "Baseline up to end of study, approximately 5 years 4 months",
"title": "Progression-free Survival",
"type": "SECONDARY"
},
{
"anticipatedPostingDate": "2026-10",
"denomUnitsSelected": "Participants",
"reportingStatus": "NOT_POSTED",
"timeFrame": "Baseline up to end of study, approximately 5 years 4 months",
"title": "Overall Survival",
"type": "SECONDARY"
},
{
"anticipatedPostingDate": "2026-10",
"denomUnitsSelected": "Participants",
"reportingStatus": "NOT_POSTED",
"timeFrame": "Baseline up to end of study, approximately 5 years 4 months",
"title": "Incidence of Lab Abnormalities",
"type": "SECONDARY"
}
]
},
"participantFlowModule": {
"groups": [
{
"description": "Participants who received an intravenous dose of 20 mg/kg ZW25 (zanidatamab) every 2 weeks (Q2W) in combination with an oral administration of 125 mg palbociclib once daily from Days 1 to 21, and an intramuscular injection of 500 mg fulvestrant Q2W for 3 doses (Cycle 1 Days 1 and 15 and Cycle 2 Day 1), and every 4 weeks (Q4W) thereafter.",
"id": "FG000",
"title": "ZW25 (Zanidatamab) + Palbociclib + Fulvestrant"
}
],
"periods": [
{
"dropWithdraws": [
{
"reasons": [
{
"groupId": "FG000",
"numSubjects": "4"
}
],
"type": "Death"
},
{
"reasons": [
{
"groupId": "FG000",
"numSubjects": "2"
}
],
"type": "Withdrawal by Subject"
},
{
"reasons": [
{
"groupId": "FG000",
"numSubjects": "1"
}
],
"type": "Lost to Follow-up"
}
],
"milestones": [
{
"achievements": [
{
"groupId": "FG000",
"numSubjects": "8"
}
],
"type": "STARTED"
},
{
"achievements": [
{
"groupId": "FG000",
"numSubjects": "1"
}
],
"type": "COMPLETED"
},
{
"achievements": [
{
"groupId": "FG000",
"numSubjects": "7"
}
],
"type": "NOT COMPLETED"
}
],
"title": "Part 1 - Dose Finding"
},
{
"dropWithdraws": [
{
"reasons": [
{
"groupId": "FG000",
"numSubjects": "10"
}
],
"type": "Death"
},
{
"reasons": [
{
"groupId": "FG000",
"numSubjects": "3"
}
],
"type": "Withdrawal by Subject"
}
],
"milestones": [
{
"achievements": [
{
"groupId": "FG000",
"numSubjects": "43"
}
],
"type": "STARTED"
},
{
"achievements": [
{
"groupId": "FG000",
"numSubjects": "30"
}
],
"type": "COMPLETED"
},
{
"achievements": [
{
"groupId": "FG000",
"numSubjects": "13"
}
],
"type": "NOT COMPLETED"
}
],
"title": "Part 2 - Dose Expansion"
}
],
"recruitmentDetails": "A total of 51 participants who met all eligibility criteria were enrolled and received treatment."
}
}
},
{
"op": "add",
"path": "/annotationSection",
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"annotationModule": {
"unpostedAnnotation": {
"unpostedEvents": [
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"type": "RESET"
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],
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},
{
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"review_question": "What source document explains this registry amendment, and does it change interpretation of the trial record?",
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