Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication ZIIHERA is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test [see Dosage and Administration ( 2.1 )]. This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies ( 14 )] . FDA label
Also known as ZW25, JZP598, ZIIHERA®
Zanidatamab · 12 trials · 26 indications
PFS is defined as the time in months from randomization to the date of first documented disease progression (as assessed by BICR according to RECIST v1.1) or death from any cause, whichever occurs first.
PFS is defined as the time from the date of randomization to the date of documented disease progression, or death from any cause.
The time from randomization to the date of documented disease progression (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1) as assessed by blinded independent central review (BICR) or death from any cause
The time from randomization to death due to any cause
Confirmed Objective Response Rate (ORR) for each cohort, based on best overall response, defined as the percentage of patients with a complete response (CR) or partial response (PR) during treatment or follow-up, assessed according to RECIST1.1, by investigator assessment and confirmed by a follow-up scan at ≥ 4 weeks from first response assessment.
Pathologic complete response (pCR) is defined as lacking all signs of cancer in the tissue samples removed in the breast or axilla (armpit) during surgery or biopsy after study treatment
The Independent Central Review (ICR) assessed cORR is defined as the proportion of participants who had a best overall response of Complete Response (CR), or Partial Response (PR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Number of participants who achieved a confirmed best overall response (BOR) of either complete response (CR) or partial response (PR) during treatment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response (CR) is defined as a disappearance of all target and non-target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of all target lesions.
Dose-limiting toxicities, defined using NCI CTCAE version 5.0, are events that 1) occur following administration of ZW25, palbociclib, and fulvestrant; and 2) meet the criteria as specified in the protocol.
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. TEAEs were coded using MedDRA v24.0.
The progression-free survival at 6 months (PFS6) is a binary endpoint variable based on the progression-free survival (PFS) time, defined as the proportion of participants having PFS time greater than or equal to 24 weeks (168 days).
Number of participants who experienced a DLT. DLTs include adverse events considered to be related to study treatment, including the evaluated dose level of ZW25, any component or combination of the components of a chemotherapy regimen, or the combination of ZW25 plus a chemotherapy regimen.
Number of participants who experienced an adverse event
Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology and chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Number of patients who experienced a DLT. DLTs include specifically defined adverse events (AEs) considered to be related to zanidatamab or evorpacept (ALX148), including combination of zanidatamab with evorpacept (ALX148)
Number of patients who experienced AEs, serious adverse events (SAEs), or adverse events of special interest (AESIs)
Number of patients who experienced a Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0
Number of patients who achieved a confirmed best overall response (BOR) of either complete response (CR) or partial response (PR) during treatment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
| Arm | Type | Description |
|---|---|---|
| Zanidatamab plus physician's choice of chemotherapy | EXPERIMENTAL | Participants with HER2-positive metastatic breast cancer (mBC) who have progressed on, or are intolerant to, previous T-DXd treatment will be randomized to receive intravenous infusion of zanidatamab plus physician's choice of chemotherapy (eribulin, or vinorelbine, or gemcitabine, or capecitabine). |
| Trastuzumab plus physician's choice of chemotherapy | ACTIVE_COMPARATOR | Participants with HER2-positive metastatic breast cancer (mBC) who have progressed on, or are intolerant to, previous T-DXd treatment will be randomized to receive intravenous infusion of trastuzumab plus physician's choice of chemotherapy (eribulin, or gemcitabine, or vinorelbine, or capecitabine). |
| Zanidatamab with Standard-of-care Therapy Arm | EXPERIMENTAL | Zanidatamab plus standard of care treatment of CisGem with or without a PD-1/L1 inhibitor. PD-1/L1 inhibitor will be physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations. |
| Standard-of-care Therapy Arm | ACTIVE_COMPARATOR | Standard of care treatment of CisGem with or without a PD-1/L1 inhibitor. PD-1/L1 inhibitor will be physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations. |
| Arm A | ACTIVE_COMPARATOR | Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP) |
| Arm B | EXPERIMENTAL | Zanidatamab plus physician's choice of CAPOX or FP |
| Arm C | EXPERIMENTAL | Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP |
| Paclitaxel and Ramucriumab | ACTIVE_COMPARATOR | - |
| Zanidatamab + Paclitaxel and Ramucirumab | EXPERIMENTAL | - |
| zanidatamab | EXPERIMENTAL | Single arm study where the experimental regimen used for all patients will be zanidatamab, administered intravenously every 3 weeks : * Patients \<70 kg: 1800 mg IV Q3W on Day 1 of each 21-day cycle * Patients ≥70 kg: 2400 mg IV Q3W on Day 1 of each 21-day cycle. |
| Zanidatamab with paclitaxel | ACTIVE_COMPARATOR | Zanidatamab in combination with chemotherapy paclitaxel |
| Zanidatamab with docetaxel and carboplatin | ACTIVE_COMPARATOR | Zanidatamab in combination with chemotherapy docetaxel and carboplatin |
| Trastuzumab and pertuzumab with docetaxel and carboplatin | ACTIVE_COMPARATOR | Trastuzumab and pertuzumab in combination with chemotherapy docetaxel and carboplatin |
| Zanidatamab treatment arm | EXPERIMENTAL | Eligible participants receiving zanidatamab treatment |
| ZW25 (Zanidatamab) Monotherapy | EXPERIMENTAL | - |
| ZW25 (zanidatamab) + palbociclib + fulvestrant | EXPERIMENTAL | Participants who received 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. |
| ZW25 + FP | EXPERIMENTAL | ZW25 plus fluorouracil (5-FU) and cisplatin |
| ZW25 + mFOLFOX6 | EXPERIMENTAL | ZW25 plus 5-FU, leucovorin, and oxaliplatin |
| ZW25 + XELOX | EXPERIMENTAL | ZW25 plus capecitabine and oxaliplatin |
| ZW25 + mFOLFOX6 with bevacizumab | EXPERIMENTAL | ZW25 plus 5-FU, leucovorin, oxaliplatin, and bevacizumab |
| ZW25 + CisGem | EXPERIMENTAL | ZW25 plus cisplatin and gemcitabine |
| Zanidatamab plus evorpacept (ALX148) | EXPERIMENTAL | - |
| ZW25 (Zanidatamab) Monotherapy and ZW25 Combination Therapy | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Zanidatamab | DRUG | Administered by intravenous infusion |
| Trastuzumab | DRUG | Administered by intravenous infusion |
| Eribulin | DRUG | Administered by intravenous infusion |
| Vinorelbine | DRUG | Administered by intravenous infusion |
| Gemcitabine | DRUG | Administered by intravenous infusion |
| Capecitabine | DRUG | Given orally |
| Cisplatin | DRUG | Administered intravenously (IV) |
| Pembrolizumab | DRUG | Administered intravenously (IV) |
| Durvalumab | DRUG | Administered intravenously (IV) |
| Tislelizumab | DRUG | Administered IV |
| Oxaliplatin | DRUG | Administered IV |
| 5-Fluorouracil | DRUG | Administered IV |
| Paclitaxel | DRUG | 80 mg/m² |
| Ramucirumab | DRUG | 8 mg/kg |
| Docetaxel | DRUG | Administered intravenously (IV) |
| Carboplatin | DRUG | Administered intravenously (IV) |
| Pertuzumab | DRUG | Administered intravenously (IV) |
| ZW25 (Zanidatamab) | DRUG | Administered intravenously |
| Palbociclib | DRUG | Administered orally |
| Fulvestrant | DRUG | Administered as an intramuscular injection |
| Fluorouracil | DRUG | Administered IV |
| Leucovorin | DRUG | Administered IV |
| Bevacizumab | DRUG | Administered IV |
| Evorpacept | DRUG | Administered IV |
| Tucatinib | DRUG | Combination therapy with ZW25 and Capecitabine - Part 3 Treatment Group 7 |
Participants are eligible to be included in the study only if all of the following criteria apply: 1. Is 18 years of age or of the legal adult age per local standard at the time of signing the informed consent. 2. Has histologically confirmed HER2-positive breast cancer according to ASCO-CAP Guidel...
Zanidatamab is an investigational monoclonal antibody being developed by Jazz Pharmaceuticals plc for HER2-expressing cancers. It is in Phase 3 clinical development for biliary tract cancer, breast cancer, gastric neoplasms, gastroesophageal adenocarcinoma, and other HER2-positive or HER2-expressing solid tumors. It has received FDA Fast Track, Orphan Drug, and Breakthrough Therapy designations.
Zanidatamab targets ERBB2, also known as HER2, and acts as an inhibitor of this receptor. By binding HER2, it is designed to interfere with signaling that drives tumor growth in HER2-expressing cancers, including HER2-positive breast cancer, biliary tract cancer, and gastroesophageal adenocarcinoma.
Zanidatamab is developed by Jazz Pharmaceuticals plc, which trades on the Nasdaq under the ticker JAZZ. Jazz Pharmaceuticals is the sponsor of the clinical development program evaluating zanidatamab across HER2-expressing solid tumors and HER2-positive breast cancer.
Zanidatamab is in Phase 3 clinical development. It is investigational and has not been approved by the FDA. The Phase 3 program includes a study comparing zanidatamab to trastuzumab, each combined with physician's choice chemotherapy, in patients with metastatic HER2-positive breast cancer.
Zanidatamab is being studied in several recruiting trials. NCT06435429 is a Phase 3 study in metastatic HER2-positive breast cancer. Phase 2 trials include NCT07192068 in solid tumors with HER2 gene alterations, NCT07102381 in neoadjuvant HER2-positive breast cancer, and NCT06695845 in HER2-expressing tumors. Total planned enrollment across these studies is approximately 980 participants.
Zanidatamab is being developed for biliary tract cancer among its HER2-expressing cancer indications. It holds FDA Orphan Drug, Fast Track, and Breakthrough Therapy designations, which are intended to support development in serious conditions. The clinical program also covers breast cancer, gastric neoplasms, and gastroesophageal adenocarcinoma.