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

Zanidatamab, a Dual HER2-Targeted Bispecific Antibody, in Patients With Unresectable Locally Advanced or Metastatic HER2-Positive Salivary Gland Cancer: A Combined Analysis of Early-Phase Studies. (PubMed, Clin Cancer Res) - P=N/A, P1, P1/2 | "Although the sample size is small, these findings support the clinical benefit of zanidatamab treatment for HER2-positive SGC."

First-in-human • Journal • Oncology • Salivary Gland Cancer • HER-2

Ziihera: Expiry of patents in China related to composition-of-matter in 2031, 2032 and 2034 (BeOne Medicines) - Annual Report 2025: Expiry of patents in China related to method of use in 2039

Patent • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

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

HER-OIC: Perioperative Zanidatamab and Chemotherapy for HER2 Positive Gastroesophageal Cancer (clinicaltrials.gov) - P1/2 | N=29 | Not yet recruiting | Sponsor: Universitaire Ziekenhuizen KU Leuven

New P1/2 trial • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • 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

A phase 2 single-arm open-label trial evaluating zanidatamab in patients with early stage HER2 positive breast cancer: The NeoZanHER Study (AACR 2026) - "Abstract is embargoed at this time."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

South Korea approves first HER2-positive bile duct cancer drug, Ziihera (Chosun Biz) - "The Ministery of Food and Drug Safety said on the 19th it approved the rare bile duct cancer treatment 'Ziihera 300 mg (zanidatamab)'....The domestic approval covers adult patients with unresectable or locally advanced or metastatic HER2-positive bile duct cancer who have previously received at least one line of systemic therapy....The Ministery of Food and Drug Safety designated the product as No. 40 under the 'Global Innovative product Fast Track (GIFT)' support system and applied priority review."

Korea approval • Biliary Tract Cancer

Zanidatamab modulates multiple pathways involved in tumor growth and survival and is efficacious post T-DXd (AACR 2026) - "Zanidatamab was efficacious on these progressed tumors with 100% regressions following the first dose. These data demonstrate HER2 domain specific binding affinity, zanidatamab impacting key cellular pathways in driving in vivo efficacy, and potential utility in a post-T-DXd population."

Biliary Cancer • Biliary Tract Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

DiscovHER PAN-206: Phase 2 tumor-agnostic study of zanidatamab in patients with previously treated human epidermal growth factor receptor 2-overexpressing solid tumors (AACR 2026) - "Abstract is embargoed at this time."

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

Zymeworks Inc…announced that the company’s partner, Jazz Pharmaceuticals, will present four abstracts featuring data from clinical trials evaluating Ziihera (zanidatamab-hrii) at the American Association for Cancer Research (AACR) Annual Meeting, being held April 17-22, 2026 in San Diego, CA. (GlobeNewswire) - "An oral presentation with results from the Phase 2 single-arm, open-label NeoZanHER trial (NCT05035836) evaluating zanidatamab for the investigational use as neoadjuvant monotherapy in patients with early-stage HER2+ breast cancer....A poster presentation detailing mechanistic and multi-omics analyses characterizing zanidatamab’s differentiated HER2 biology, including dual, domain-specific binding and downstream effects on key cellular signaling pathways, with insights into activity in models following progression on trastuzumab deruxtecan (T-DXd)."

Clinical data • Gastroesophageal Junction Adenocarcinoma • HER2 Positive Breast Cancer • Solid Tumor

BGB-A317-290-LTE1: Study of Tislelizumab, Pamiparib, and Other Investigational Agents in Participants With Advanced Malignancies (clinicaltrials.gov) - P3 | N=430 | Enrolling by invitation | Sponsor: BeOne Medicines | Trial completion date: Dec 2026 ➔ Jul 2026 | Trial primary completion date: Dec 2026 ➔ Jul 2026

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

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

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

EmpowHER 208: A Phase 2, randomized, multicenter, open-label neoadjuvant study evaluating zanidatamab in combination with chemotherapy in participants with HER2-positive breast cancer combination with chemotherapy in participants with HER2-positive breast cancer (clinicaltrialsregister.eu) - P1/2 | N=60 | Not yet recruiting | Sponsor: Jazz Pharmaceuticals Ireland Limited

New P1/2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Negative Breast Cancer • Inflammatory 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

SAFIR ABC10: Targeted maintenance therapy versus first-line standard of care in advanced biliary cancer. (BWG 2026) - "Introduction: The first-line standard of care (1L-SoC) for advanced biliary tract cancers (ABC), a heterogeneous group of malignancies of the bile ducts and gallbladder, is cisplatin and gemcitabine combined with anti-PD-(L)1...They were randomized to SoC (18 pts, 33%), Futibatinib (13 pts, 24%), Ivosidenib (13 pts, 24%), Zanidatamab (5 pts, 9%), Neratinib-Trastuzumab (1 pt, 2%), Binimetinib-Encorafenib (4 pts, 8%)... SAFIR ABC10 is recruiting at a high pace, with > 50% of the target sample screened, and 34.5% (55/159 pts) randomized. Targetable alterations were found in 104 pts (29%) of patients (including 1% MSI-High pts), of which 55 are randomized. Belgium centres are currently open(ing)."

Clinical • Metastases • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology • Solid Tumor • BRAF • FGFR2 • HER-2 • IDH1

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

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 | " The ongoing HARBOR trial is a multicenter, open-label, single-arm, phase II study designed to evaluate the efficacy and safety of a selective bladder-preservation strategy following neoadjuvant zanidatamab plus tislelizumab and gemcitabine-cisplatin (GC) in patients with HER2-positive (immunohistochemistry 2+ or 3+) MIBC (cT2-4aN0-1M0). Key secondary endpoints include 1- and 2-year bladder-intact disease-free survival (BI-DFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), safety, and patient-reported quality of life (QoL). Registration number: ChiCTR2500110562."

Clinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • 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

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 | "Secondary end points were bladder-preservation rate, OS and safety. Our study estimated a RFS rate at 12 months was no less than 75.5% and the study would enroll 20 pts."

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

In January 2026, the New Drug Submission for Ziihera was approved by Health Canada for the treatment of adults with previously treated, unresectable locally advanced or metastatic HER2+ (IHC 3+) biliary tract cancer, as monotherapy. (Zymeworks Press Release)

Canada approval • Biliary Tract Cancer

Zymeworks Inc…and Royalty Pharma plc…announced an agreement for $250 million in funding from Royalty Pharma in the form of a non-recourse royalty-backed note with repayments due from 30% of worldwide tiered royalties on Ziihera (zanidatamab-hrii) owed to Zymeworks from Jazz Pharmaceuticals (Jazz) and BeOne Medicines (BeOne). (GlobeNewswire) - "Repayment of the note will be secured by 30% of future royalties from the global sales of Ziihera, generated under collaboration agreements with partners Jazz and BeOne, equating to an approximately low to mid-single digit upward tiering royalty up to a pre-specified repayment limit....Under the collaboration agreement with Jazz, Zymeworks is eligible to receive tiered royalties of 10% to high teens on global (outside of Asia (other than Japan), Australia and New Zealand) annual sales of Ziihera up to $2.0 billion and 20% on annual net sales above $2.0 billion."

Financing • Biliary Tract Cancer • Gastric Cancer

UC-GMP-2505: Clinical trial evaluating the activity of zanidatamab for the treatment of patients with solid tumors with an alteration of the HER2 gene (clinicaltrialsregister.eu) - P1/2 | N=105 | Recruiting | Sponsor: Unicancer

New P1/2 trial • Endometrial Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor

JZP598-206: A Phase 2 study of zanidatamab in patients with HER2-expressing tumors (clinicaltrialsregister.eu) - P1/2 | N=50 | Not yet recruiting | Sponsor: Jazz Pharmaceuticals Ireland Limited

New P1/2 trial • Breast Cancer • Gallbladder Cancer • Gastric Cancer • Oncology • Solid Tumor

Anticipated R&D Milestones (Businesswire) - "TEVIMBRA: Supplemental Biologics License Application submissions in U.S. and China for the treatment of adult patients with first-line HER2-positive GEA in combination with zanidatamab: 1H 2026; Japan regulatory action for the treatment of adult patients with first-line gastric cancer: 2H 2026...Sonrotoclax (BCL2 inhibitor): FDA regulatory action on New Drug Application as monotherapy treatment of adult patients with R/R MCL: 1H 2026; Phase 3 trial initiation for the treatment of adult patients with R/R multiple myeloma t(11;14): 2H 2026...BGB-16673 (BTK CDAC): Phase 2 potential accelerated approval submission (if data support) for the treatment of adult patients with R/R CLL: 2H 2026."

Approval • Filing • New P3 trial • Chronic Lymphocytic Leukemia • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Mantle Cell Lymphoma • Multiple Myeloma