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

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 | "Funded by Jazz Pharmaceuticals, BeOne Medicines Ltd Clinical Trial Registration Number: NCT05152147 The full, final text of this abstract will be available on Jan 08 at 10:00 AM EST."

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

Pre-ispy trial: a phase i/ib oncology platform program (pre-i-spy-p1) nct05868226 (SABCS 2025) - P1 | "The current arms under study are PRE1 ALX-148/T-DXd; PRE2 tucatinib/zanidatamab; and PRE3 vidutolimod/cemiplimab. Conclusion The PRE-ISPY phase I/Ib trial has been successfully implemented nationally as part of the Consortium of I-SPY trials. Once safety is established, promising regimens can be rapidly transitioned to I-SPY2.2, K-SPY or other phase II/III trials."

P1 data • Breast Cancer

Combinatory treatments of VRN101099 with antibody therapies for HER2-driven breast cancer (SABCS 2025) - "In BT474 or SKBR3, HER2 amplified breast cancer cells, xenograft models with subcutaneous or intracranial implantation, VRN101099 showed combinatory and synergistic anti-tumor effects with Trastuzumab, Pertuzumab, T-DM1, T-DXd, and Zanidatamab. The first-in-human dose escalation study of VRN101099 monotherapy will determine the maximal tolerable dose, and an optimal dose finding study for the combination will be followed."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR • HER-2

Zanidatamab Combined With Chemotherapy as Neoadjuvant Therapy for HER2-high Expression G/GEJC (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Xijing Hospital

New P2 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

EmpowHER-208: A phase 2 neoadjuvant study of zanidatamab in combination with chemotherapy in patients with stage II-III HER2-positive early breast cancer (SABCS 2025) - "One standard-of-care (SOC) neoadjuvant regimen for patients with stage II-III HER2+ early breast cancer is docetaxel (T) and carboplatin (C) + dual HER2-directed therapy (trastuzumab [H] and pertuzumab [P]; collectively TCHP), with single-agent taxane (docetaxel or paclitaxel [T]) + HP regimens becoming increasingly common...Patients who do not achieve pCR will receive fourteen 3-week cycles of SOC ado-trastuzumab emtansine (T-DM1). Adjuvant endocrine therapy, extended neratinib, radiotherapy, or additional chemotherapy (ZT arm only) may be administered based on investigator preference and institutional SOC. The primary endpoint is pCR rate by blinded local assessment. Key secondary endpoints include pathologic response by residual cancer burden score at time of surgery, breast-conserving surgery rate, safety and tolerability, event-free survival, and overall survival."

Clinical • Combination therapy • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2

Jazz Pharmaceuticals to Present Pivotal Phase 3 Results of Ziihera (zanidatamab-hrii) Combinations in First-Line HER2-Positive Locally Advanced or Metastatic Gastroesophageal Adenocarcinoma at the 2026 ASCO Gastrointestinal Cancers Symposium (PRNewswire) - "The Phase 3 HERIZON-GEA-01 trial results in first-line HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA) were accepted as a late-breaking presentation. Additionally, a new post-hoc overall survival (OS) analysis from the HERIZON-BTC-01 Phase 2b trial in previously treated HER2+ biliary tract cancer (BTC) will be presented, providing further information for this approved indication."

Clinical data • Late-breaking abstract • Biliary Tract Cancer • Gastroesophageal Junction Adenocarcinoma

Phase 1b/2 Study of Zanidatamab in Combination with Tislelizumab and Chemotherapy in First-Line HER2-Positive Gastric/Gastroesophageal Junction Adenocarcinoma. (PubMed, Clin Cancer Res) - P1/2, P3 | "Zanidatamab, in combination with tislelizumab and CAPOX, demonstrated clinically meaningful antitumor activity with a manageable safety profile as first-line therapy for patients with HER2+ GC/GEJC. These results support further development of zanidatamab and tislelizumab with chemotherapy in this patient population in the ongoing phase 3 HERIZON-GEA-01 trial (NCT05152147)."

Journal • P1/2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

…Final results from the phase 2 HERIZON-BTC-01 trial (NCT04466891) published in JAMA Oncology (Cancer Network) - "Data showed a confirmed objective response rate (ORR) of 41.3% (95% CI, 30.4%-52.8%) along with a median duration of response (DOR) of 14.9 months (95% CI, 7.4-24.0). Additionally, the median overall survival (OS) was 15.5 months (95% CI, 10.4-18.7). Among 62 patients with immunohistochemistry (IHC) tumors of 3+, zanidatamab elicited a confirmed ORR of 51.6% (95% CI, 38.6%-64.5%) and a median OS of 18.1 months (95% CI, 12.2-22.9). Regarding 18 patients with IHC 2+ status, 1 patient experienced a partial response for a confirmed ORR of 5.6% (95% CI, 0.1%-27.3%); the median OS was 5.2 months (95% CI, 3.1-10.2)."

P2 data • Biliary Tract Cancer

Phase II Basket Trial: Zanidatamab Plus Tislelizumab in HER2-Positive GI Tumors (UNION-HER2-BASKET) (clinicaltrials.gov) - P2 | N=70 | Not yet recruiting | Sponsor: Tao Zhang

New P2 trial • Pan tumor • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

AcSé HER2: Clinical Trial Evaluating the Activity of Zanidatamab for the Treatment of Patients With Solid Tumors With an Alteration of the HER2 Gene. (clinicaltrials.gov) - P2 | N=105 | Active, not recruiting | Sponsor: UNICANCER | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Colorectal Cancer • Endometrial Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor

HER2-targeted therapy shows promising results in rare bile duct cancers (MD Anderson Press Release) - "Zanidatamab...delivered clinically meaningful and durable responses for patients with HER2-positive biliary tract cancer (BTC), according to final results from the HERIZON-BTC-01 clinical trial led by researchers at The University of Texas MD Anderson Cancer Center. In this clinical trial, zanidatamab demonstrated an objective response rate of 41.3% and a median duration of response of 15.5 months, while patients whose tumors showed strongest levels of HER2 overexpression experienced even greater benefit – a 51.6% response rate and a median duration of response of 18.1 months."

P2 data • Biliary Tract Cancer

Zanidatamab in HER2-Positive Metastatic Biliary Tract Cancer: Final Results From HERIZON-BTC-01. (PubMed, JAMA Oncol) - No abstract available

Journal • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • HER-2

Systematic Literature Review (SLR) of First-Line (1L) Treatments of Patients With Advanced or Metastatic HER2-Positive Gastroesophageal Adenocarcinoma (GEA) (ISPOR-EU 2025) - "Recently, a phase 3 RCT demonstrated the anti-PD-1 antibody pembrolizumab plus trastuzumab and chemotherapy improved OS versus trastuzumab and chemotherapy alone in the subset of patients with HER2-positive gastric/GEJ cancer and a PD-L1 CPS score ≥1 (20.1 months vs 15.7 months). Dual HER2-inhibition with the introduction of pertuzumab to trastuzumab and chemotherapy did not further improve patient outcomes in the rest of the RCTs. Other immunotherapy and/or biomarker-driven combinations, such as with bevacizumab, nivolumab, and zanidatamab, were studied in small RCTs or single-arm trials... There is no new HER2-targeted treatment since trastuzumab that has demonstrated OS benefits in combination regimens for 1L HER2-positive GEA. Dual blockade of HER2 and PD-L1, with the addition of immunotherapy to trastuzumab-based chemotherapy, improved survival for the subset of patients who also expressed PD-L1. Multiple trials are currently underway to investigate novel regimens..."

Clinical • IO biomarker • Metastases • Review • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

Zymeworks Inc…announced a novel strategic initiative focused on optimizing future cash flows from Ziihera (zanidatamab-hrii), other licensed products and other healthcare assets. (GlobeNewswire) - "For Ziihera, under the Company’s existing arrangements with Jazz and BeOne, Zymeworks has the potential to receive substantial near-term milestone payments related to future regulatory approvals in GEA totaling $440.0 million, as follows: USA - $250.0 million; EU - $100.0 million; Japan - $75.0 million; China - $15.0 million. The Company also expects that royalty revenue from Ziihera sales will increase as potential regulatory approvals are obtained in global markets for GEA. In addition, Zymeworks could be eligible to receive future milestones and increased royalties from the development, regulatory approval, and commercialization of any additional indications for Ziihera by Jazz and BeOne, including breast cancer."

Financing • Breast Cancer • Gastroesophageal Junction Adenocarcinoma

Zymeworks Announces Positive HERIZON-GEA-01 Phase 3 Results Supporting Ziihera (zanidatamab-hrii) as HER2-Targeted Agent-of-Choice and New Standard of Care in First-Line HER2-Positive Locally Advanced or Metastatic Gastroesophageal Adenocarcinoma (Yahoo Finance) - "Both Ziihera plus chemotherapy and Ziihera plus Tevimbra and chemotherapy demonstrated highly statistically significant and clinically meaningful improvements in progression-free survival (PFS) compared to the control arm, trastuzumab plus chemotherapy...The trial is ongoing with an additional planned OS interim analysis for Ziihera plus chemotherapy currently expected in mid-2026...Jazz expects to submit a supplemental Biologics License Application in the first half of 2026 to support Ziihera as a first-line treatment for patients with HER2+ locally advanced or metastatic GEA for use as part of a standard chemotherapy regimen with or without Tevimbra."

FDA filing • P3 data: top line • Gastroesophageal Junction Adenocarcinoma

Therapeutic Potential of Bispecific Antibodies in Adenocarcinoma: A Targeted Literature Review (ISPOR-EU 2025) - "Molecules more frequently studied are AK104 (PD-1/CTLA-4 bispecific), zanidatamab (anti-HER2), and CDX-527 (PD-L1/CD27)...In hepatocellular carcinoma, AK104 plus lenvatinib achieved a disease control rate (DCR) of 77.8%... Our findings indicate promising efficacy of BsAbs in gastric, hepatic, and HER2-positive adenocarcinomas, with encouraging disease control and survival outcomes. While most TRAEs were manageable, frequent higher-grade events highlight the need for close monitoring. Biomarker-enriched trials may help optimize safety and patient selection."

IO biomarker • Review • Gastroesophageal Junction Adenocarcinoma • Hepatocellular Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • CD27 • CTLA4 • PD-1 • PD-L1

Advancing Targeted Therapy: Exploring the HORIZON Study and Novel HER2 Strategies in Gastric Cancer - "An expert panel convened to discuss the rapidly advancing treatment landscape in upper gastrointestinal cancers, focusing on the integration of perioperative immunotherapy, biomarker-driven decision-making, and novel therapeutic approaches such as tislelizumab, zanidatamab, and emerging antibody-drug conjugates (ADCs)."

Video

From Progress to Promise: Advancing Biomarkers, ADCs, and the Next Wave of Innovation - "An expert panel convened to discuss the rapidly advancing treatment landscape in upper gastrointestinal cancers, focusing on the integration of perioperative immunotherapy, biomarker-driven decision-making, and novel therapeutic approaches such as tislelizumab, zanidatamab, and emerging antibody-drug conjugates (ADCs)."

Biomarker • Video

Zanidatamab in combination with docetaxel in first-line HER2-positive breast cancer: results from an open-label, multicenter, phase Ib/II study. (PubMed, ESMO Open) - "Zanidatamab demonstrated efficacy and a manageable and tolerable safety profile with docetaxel as first-line treatment in patients with HER2-positive breast cancer. These data support the further development of zanidatamab in this patient population."

Journal • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Respiratory Diseases • Solid Tumor • HER-2

Zanidatamab on the HERizont in HER2+ biliary carcinomas (DGHO 2025) - "Sponsored by JAZZ."

Biliary Cancer • Oncology • Solid Tumor • HER-2

Business Updates:…Ziihera (zanidatamab-hrii) (PRNewswire) - "Net product sales were $8.3 million in 3Q25 following product launch in December 2024."

Sales • Biliary Tract Cancer

Key Highlights (PRNewswire.co.uk) - "Top-line PFS data from zanidatamab in Phase 3 1L GEA expected in 4Q25; updated intent-to-treat population for PFS to include all patients enrolled in the trial."

P3 data: top line • Esophageal Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

Iambic Announces Research Collaboration with Jazz Pharmaceuticals for IAM1363 and Zanidatamab Combination Cohort in HER2-Positive Breast Cancer (Businesswire) - "Under the agreement, Jazz will provide zanidatamab (Ziihera), a HER2-targeted bispecific antibody, at no cost to Iambic for evaluation in combination with IAM1363....The combination will be studied in patients with HER2-positive breast cancer....As part of the Phase 1/1b IAM1363-01 study, Iambic will initiate a cohort in patients with HER2-positive breast cancer to evaluate IAM1363 in combination with zanidatamab and capecitabine."

Commercial • Trial status • HER2 Positive Breast Cancer

Neoadjuvant Zanidatamab + Tislelizumab + Gemcitabine/Cisplatin for Selective Bladder Preservation in HER2-Positive MIBC (ChiCTR) - P2 | N=25 | Not yet recruiting | Sponsor: Fujian Medical University Union Hospital; Fujian Medical University Union Hospital

New P2 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Opportunities and Approaches to Optimising Advanced Cholangiocarcinoma Outcomes in the Era of Targeted Therapies: A Narrative Review. (PubMed, Oncol Ther) - "If the tumour is unresectable, the recommended first-line treatment is cisplatin + gemcitabine + durvalumab a programmed cell death ligand 1 [PD-L1] inhibitor or pembrolizumab a programmed cell death protein 1 [PD-1] inhibitor. The development of targeted therapies has led to these treatments being recommended as second- or third-line therapy for patients with actionable gene alterations, while 5-fluorouracil-based chemotherapy is recommended for those without. Robust data support the use of ivosidenib in patients with IDH1 mutations (phase 3), and phase 2 trials showed efficacy of pemigatinib and futibatinib for patients with FGFR2 gene fusions, trastuzumab deruxtecan and zanidatamab for patients with HER2 overexpression/amplification, and dabrafenib + trametinib for patients with BRAFV600E mutations. It is hoped that wider dissemination of the content from this meeting will improve outcomes of patients with CCA by encouraging earlier referral,..."

IO biomarker • Journal • Review • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • FGFR2 • HER-2 • IDH1