Ziihera (zanidatamab-hrii) / Zymeworks, BeOne Medicines, Jazz - LARVOL DELTA

Zanidatamab (Zani) + chemotherapy (Chemo) for patients (Pts) with HER2-expressing metastatic breast cancer (mBC): Final results of a phase I trial (ESMO-BC 2025) - P1 | "We report the final analysis of a phase I trial of zani + chemo in pts with HER2-expressing mBC. Part 3 of the phase I trial (NCT02892123) evaluated zani + chemo (paclitaxel [pac], capecitabine [cap] or vinorelbine [vin]) or zani + cap + tucatinib (tuc) in pts with HER2-expressing mBC...Prior (>5% of pts) anti-HER2 therapies included trastuzumab (93%), T-DM1 (91%), pertuzumab (80%), lapatinib (24%), T-DXd (9%), tuc (9%), and neratinib (7%)... Zani + chemo had a manageable safety profile and good tolerability with promising antitumour activity and durable responses in heavily pretreated pts with HER2-expressing mBC. Among pts with HER2+ mBC with prior HER2-targeted regimens, adding zani to chemo showed encouraging PFS."

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Long-term outcomes and overall survival (OS) for zanidatamab + chemotherapy in HER2-positive (HER2+) advanced or metastatic gastroesophageal adenocarcinoma (mGEA): 4-year follow-up of a phase 2 trial. (ASCO 2025) - P2 | " The phase 2 trial (NCT03929666) evaluated zani + chemo (mFOLFOX6, CAPOX, or FP) in the 1L treatment of mGEA... After a median 4-year follow-up, zani + chemo demonstrated clinically meaningful efficacy in the 1L treatment of HER2+ mGEA, with durable responses and a median OS > 3 years, and a manageable safety profile. Zani + chemo markedly reduced total plasma ctDNA levels early in treatment of mGEA. aResponse evaluable (n = 42 and 37)."

Clinical • Metastases • P2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Oncology • Solid Tumor • HER-2

Zanidatamab plus chemotherapy as first-line treatment for patients with HER2-positive advanced gastro-oesophageal adenocarcinoma: primary results of a multicentre, single-arm, phase 2 study. (PubMed, Lancet Oncol) - P2 | "Zanidatamab plus chemotherapy as first-line treatment of HER2-positive advanced gastro-oesophageal adenocarcinoma demonstrated clinically meaningful and durable antitumour activity, with a manageable safety profile."

Journal • P2 data • Acute Kidney Injury • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Nephrology • Oncology • Renal Disease • Solid Tumor • HER-2

Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): Primary analysis from HERIZON-GEA-01. (ASCO-GI 2026) - P3 | "Background: HERIZON-GEA-01 (NCT05152147) is a global, open-label, phase 3 trial of zanidatamab (dual HER2-targeted bispecific antibody) + CT ± tislelizumab (anti–PD-1) vs trastuzumab (tras) + CT in 1L HER2+ mGEA. Eligible patients (pts) with previously untreated HER2+ mGEA, regardless of PD-L1 status, were randomized (1:1:1) to zanidatamab (1800 mg [12 mo) vs tras + CT. Zanidatamab + tislelizumab + CT also provided a statistically significant and clinically meaningful OS benefit (mOS >26 mo). The trial is ongoing with additional OS analyses planned for zanidatamab + CT."

Clinical • Late-breaking abstract • Metastases • Esophageal Adenocarcinoma • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Selective bladder preservation after neoadjuvant zanidatamab combined with tislelizumab and chemotherapy in patients with HER2-positive muscle-invasive bladder cancer (HARBOR): A multicenter study. (ASCO-GU 2026) - P2 | "Clinical Trial Registry Number: ChiCTR2500110562. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Clinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • HER-2

Primary results from a phase 2a study of zanidatamab (zani) + palbociclib (palbo) + fulvestrant (fulv) in HER2+/HR+ metastatic breast cancer (mBC) (SABCS 2023) - P2 | " Eligible pts had HER2+ (by local HER2 testing) and HR+, unresectable, locally advanced or mBC; ECOG PS ≤1; prior treatment with at least trastuzumab, pertuzumab, and T-DM1; and no prior CDK4/6 inhibitor...In the metastatic setting, pts received a median (range) of 4 (1-12) prior systemic regimens, 3 (1-10) prior different HER2-targeted therapies, and 1 (0-5) prior endocrine therapy; 12 (24%) pts had prior T-DXd and 11 (22%) had prior fulv... Zani + palbo + fulv showed a promising PFS6 and mPFS with durable responses. The safety profile was manageable. These results support further development of a novel chemotherapy-free treatment regimen for heavily pretreated pts with HER2+/HR+ mBC."

Late-breaking abstract • Metastases • P2a data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Zanidatamab plus palbociclib and fulvestrant in previously treated patients with hormone receptor-positive, HER2-positive metastatic breast cancer: primary results from a two-part, multicentre, single-arm, phase 2a study. (PubMed, Lancet Oncol) - P2 | "Zanidatamab plus palbociclib and fulvestrant was generally safe and showed promising antitumour activity, supporting further evaluation of this chemotherapy-free triplet regimen."

Journal • P2a data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • HER-2

Advancing HER2-Targeted Therapy in GI Cancers (YouTube) - "The treatment landscape for HER2-positive gastroesophageal cancer is rapidly evolving, with zanidatamab emerging as a new option following years of limited progress beyond trastuzumab. Dr. John Strickler joins us to share insights on how recent FDA approvals and novel agents are transforming outcomes in this complex disease setting."

Video

Paclitaxel and Ramucirumab +/- Zanidatamab in HER2 Postive Advanced Gastroesophageal Adenocarcinoma (clinicaltrials.gov) - P2 | N=168 | Recruiting | Sponsor: Canadian Cancer Trials Group | Trial completion date: Jun 2026 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

EMPOWER01: A phase II study of zanidatamab combined with bacillus Calmette-Guerin (BCG) in HER2-positive high-risk non-muscle-invasive bladder cancer (HR NMIBC). (ASCO-GU 2026) - P4 | "Clinical Trial Registry Number: ChiCTR2200067158. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • HER-2

Zanidatamab (Zani) + chemotherapy (CT) in first-line (1L) human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic colorectal cancer (mCRC) (ESMO 2024) - P2 | "Here, we report preliminary safety and antitumour activity of 1L zani + CT ± bevacizumab (bev) in HER2+ mCRC. This phase 2, open-label study (NCT03929666) is evaluating 1L zani + CT ± bev in pts with HER2-expressing (IHC 3+) or amplified (FISH+) mCRC...Eligible pts had an ECOG performance status (ECOG PS) of 0 or 1, had not received ≥1 prior cycle of a fluorouracil (5-FU)-based regimen for mCRC, and had no prior HER2-targeted agents. Pts received zani (1200 mg: pts <70 kg; 1600 mg: pts ≥70 kg; intravenous [IV] every two weeks) + mFOLFOX6-2 (leucovorin 400 mg/m2 IV and oxaliplatin 85 mg/m2 IV on days 1 and 15; 5-FU 1200 mg/m2/day IV on days 1-2 and 15-16) ± bev per physician's choice (5 mg/kg IV on days 1 and 15)... Zani ± bev demonstrated encouraging antitumor activity with a generally manageable safety profile in 1L HER2+ mCRC."

Clinical • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

New Data Demonstrate CD47 Expression Level Helps Predict Response to ALX Oncology’s Evorpacept in Combination with Ziihera (zanidatamab-hrii) in Advanced HER2-Positive Breast Cancer (The Manila Times) - "The additional exploratory analysis, conducted to identify biomarkers of response to the evorpacept/zanidatamab combination, shows that responses in this trial were largely restricted to patients with higher CD47 expression....The full biomarker analysis from the Phase 1b/2 clinical trial has been submitted to an upcoming scientific congress for presentation."

P1/2 data • HER2 Breast Cancer • HER2 Positive Breast Cancer

Neoadjuvant zanidatamab for stage I node negative HER2 positive breast cancer (BC) (ESMO-BC 2023) - "Background Outcome of patients (pts) w/ stage I node neg HER2+ treated w/ wkly paclitaxel x 12 doses and trastuzumab x 1yr is excellent (10yr RFS 96%)...Three received tamoxifen and 3 letrozole...Conclusions Neoadjuvant zanidatamab for 3 months showed significant efficacy, (pCR/RCB-1 64%) w/ acceptable safety profile in pts w/ stage I node neg HER2+ BC. The trial is ongoing and has been modified to increase treatment duration to 5mths (10 cycles)."

Clinical • Acne Vulgaris • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CD4 • HER-2

Novel HER2-Targeted Bispecific Improves Outcomes in Patients With Gastroesophageal Cancer (THE ASCO POST) - "'What I think is remarkable about this study is to see a duration of response that is truly meaningful: 20 months with zanidatamab and chemotherapy, in addition to a positive benefit in progression-free survival and at least a trend toward an overall survival benefit with just zanidatamab and chemotherapy,' Dr. Shroff said."

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Multimodal treatment and tumour biology-driven long-term survival in PSC-associated hilar cholangiocarcinoma: A case report. (PubMed, Med Int (Lond)) - "The tumour was HER2-positive, and the compassionate use of zanidatamab was initiated following progression on standard therapies...The prolonged survival of the patient despite delayed transplant and metastatic recurrence suggests that PSC-related hCCA may follow a more indolent course compared to de novo cases. Future efforts are required to focus on tumour profiling and stratified therapeutic approaches to better guide treatment in this complex disease."

Journal • Biliary Cancer • Cholangiocarcinoma • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Oncology • Solid Tumor • Transplantation • HER-2

Survival outcomes for zanidatamab-hrii compared to chemotherapy in previously treated HER2-positive (IHC3+) biliary tract cancer (BTC): HERIZON-BTC-01 vs a real-world (RW) external control arm (ECA). (ASCO 2025) - P2 | " HERIZON-BTC-01 (NCT04466891) evaluated zanidatamab-hrii (20 mg/kg IV every 2 weeks) in patients with HER2-amplified, unresectable locally advanced or metastatic BTC (gallbladder cancer [GBC], intra-/extra-hepatic cholangiocarcinoma [ICC/ECC]) who had received prior gemcitabine-containing therapy... Among patients with previously-treated HER2-positive (IHC3+) BTC, zanidatamab-hrii resulted in longer survival, including a >14 month increase in median OS, vs ECA patients treated with chemotherapy."

Clinical • Real-world • Real-world evidence • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology • Solid Tumor • HER-2

Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study. (PubMed, Lancet Oncol) - P1 | "These results support that HER2 is an actionable target in various cancer histologies, including biliary tract cancer and colorectal cancer. Evaluation of zanidatamab continues in ongoing studies."

Journal • P1 data • Biliary Cancer • Biliary Tract Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Zanidatamab (zani), a HER2-targeted bispecific antibody, in combination with docetaxel as first-line therapy (1L) for patients (pts) with advanced HER2-positive breast cancer (BC): Updated results from a phase 1b/2 study. (ASCO 2023) - P1b/2 | "Zani combined with docetaxel demonstrated promising antitumor activity as 1L therapy for advanced HER2+ BC, with a manageable safety profile. Clinical trial information: NCT04276493. >*Four pts without any postbaseline tumor assessments were excluded from the EE analysis set.Data cut off: November 22, 2022.†Censored."

Clinical • Combination therapy • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Zanidatamab in previously-treated HER2-positive (HER2+) biliary tract cancer (BTC): Overall survival (OS) and longer follow-up from the phase 2b HERIZON-BTC-01 study. (ASCO 2024) - P2 | " HERIZON-BTC-01 (NCT04466891) is an ongoing phase 2b trial assessing zanidatamab (20 mg/kg IV Q2W) in patients with HER2/ERBB2 gene amplification and immunohistochemistry (IHC) 2+ or 3+ (Cohort 1; HER2+); or 0 or 1+ (Cohort 2) locally advanced, unresectable, or metastatic BTC (gallbladder cancer, intra/extrahepatic cholangiocarcinoma) who received prior gemcitabine-containing treatment. With close to 2 years of median follow-up, zanidatamab demonstrated a median OS of 15.5 months and a median duration of response of 14.9 months (an increase compared with the initial report) in previously-treated patients with HER2+ BTC; a patient population with significant unmet need. With additional follow-up, safety remained manageable. A phase 3 trial of zanidatamab in the first-line setting for patients with metastatic BTC is planned."

Clinical • P2b data • Anemia • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Oncology • Pneumonia • Solid Tumor • HER-2

Results from the pivotal phase (Ph) 2b HERIZON-BTC-01 study: Zanidatamab in previously-treated HER2‑amplified biliary tract cancer (BTC). (ASCO 2023) - P2b | " HERIZON-BTC-01, an open-label, global Ph 2b study (NCT04466891), evaluated zani (20 mg/kg IV every 2 wks) in pts with HER2-amplified, locally advanced unresectable or metastatic BTC (gallbladder cancer [GBC], intra-/extra-hepatic cholangiocarcinoma [ICC/ECC]) who had received prior gemcitabine-containing therapy; pts with prior HER2-targeted therapies were excluded. Results of the pivotal HERIZON-BTC-01 study indicate that the HER2 bispecific antibody zani demonstrates rapid, durable responses with a manageable safety profile in pts with tx-refractory HER2-positive BTC. Given these data, zani continues to be developed as a tx option in HER2-positive BTC. Clinical trial information: NCT04466891."

Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Pneumonia • Solid Tumor • HER-2

Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study. (PubMed, Lancet Oncol) - P2b | "Zanidatamab demonstrated meaningful clinical benefit with a manageable safety profile in patients with treatment-refractory, HER2-positive biliary tract cancer. These results support the potential of zanidatamab as a future treatment option in HER2-positive biliary tract cancer."

Journal • Metastases • P2b data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Asia subgroup overall survival and long-term follow-up results of the phase IIb HERIZON-BTC-01 study: Zanidatamab in previously treated human epidermal growth factor receptor 2 (HER2)-amplified biliary tract cancer (BTC) (ESMO Asia 2024) - P2 | "Methods This open-label, phase IIb study enrolled adults with HER2-amplified, unresectable, locally advanced/metastatic BTC, and ≥1 prior gemcitabine-containing systemic therapy. d Greenwood. CI, confidence interval."

Clinical • P2b data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Zanidatamab + chemotherapy for first-line (1L) treatment of HER2+ advanced or metastatic gastro-oesophageal adenocarcinoma (mGEA): New and updated data from a phase II trial (ESMO 2024) - P2 | "Endpoints included confirmed objective response rate (cORR), duration of response (DoR), progression-free survival (PFS), OS and rate/severity of adverse events (AEs). As of 17 Jan 2024, 46 pts were enrolled (zani + mFOLFOX6 [n=24], CAPOX [n=20] or FP [n=2]); 41 (89%) had tumours that were centrally confirmed as HER2+ mGEA (ccHER2+; IHC 3+/FISH+ [n=36; 78%] or IHC 2+/FISH+ [n=5; ‍ 11%])... With >3.4 years of median follow-up, zani + chemo continues to show promising antitumour activity, with an encouraging OS, and a manageable safety profile for 1L treatment in pts with HER2+ mGEA. A global phase 3 HERIZON-GEA-01 is investigating zani + chemo ± tislelizumab for 1L treatment of HER2+ mGEA."

Clinical • Metastases • P2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

DiscovHER PAN-206: Phase 2 Tumour-Agnostic Study of Zanidatamab in Patients With Previously Treated Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Solid Tumours (SGO 2026) - No abstract available

Clinical • P2 data • Pan tumor • Oncology • Solid Tumor • HER-2

Preliminary results from a phase I study using the bispecific, human epidermal growth factor 2 (HER2)-targeting antibody-drug conjugate (ADC) zanidatamab zovodotin (ZW49) in solid cancers (ESMO 2022) - P1 | "Conclusions ZW49 has a manageable safety profile with encouraging single-agent antitumor activity in heavily pretreated pts with HER2+ cancers. Enrollment continues at 1.75 mg/kg QW in DE and 1.5 mg/kg QW in DX."

P1 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor