Ziihera (zanidatamab-hrii) / Zymeworks, BeOne Medicines, Jazz, Royalty - 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 | "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

Zanidatamab in patients with early stage HER2-positive breast cancer: the NeoZanHER phase 2 single-arm open-label trial. (PubMed, Nat Commun) - P2 | "Further research is needed to refine patient selection. This study is registered at ClinicalTrials.gov (NCT05035836)."

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

Comparative Efficacy and Safety of Biomarker-Guided Targeted Therapies Versus Conventional Treatment in Advanced Biliary Tract Cancer: A Systematic Review and Network Meta-Analysis (ACG 2026) - "14 studies involving 3,842 patients were included, comprising 2,116 males (55.1%) and 1,726 females (44.9%), with median age ranging from 58â69 years. Evaluated therapies included FGFR inhibitors (pemigatinib, futibatinib, infigratinib), the IDH1 inhibitor ivosidenib, HER2-directed regimens (trastuzumab-based therapies and zanidatamab), dabrafenib plus trametinib, zenocutuzumab, and conventional chemotherapy/immunotherapy controls. Most patients had metastatic disease (81.6%), ECOG 0â1 status (87.3%), and prior systemic therapy exposure."

Biomarker • IO biomarker • Metastases • Retrospective data • Review • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • FGFR2 • IDH1 • NRG1

HERIZON-GEA-01: Exploratory analysis of response characteristics and PFS2 in advanced or metastatic gastroesophageal adenocarcinoma (mGEA) (ESMO-GI 2026) - P3 | "Background HERIZON-GEA-01 (NCT05152147) is a global phase 3 trial evaluating zanidatamab (zani) + chemotherapy (CT) ± tislelizumab (tis) vs trastuzumab (tras) + CT in treatment (tx)-naive patients (pts) with HER2+ mGEA. Prolonged PFS2 in experimental arms suggests that pts still benefit from subsequent tx. Safety in responders was similar to the overall safety population."

Metastases • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PD-L1

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

Beyond trastuzumab: redefining first-line HER2-positive gastroesophageal cancer with bispecific HER2 targeting. (PubMed, J Gastrointest Oncol) - No abstract available

Journal • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor • HER-2

Zanidatamab in patients with HER2-positive biliary tract cancer (BTC) previously treated with PD-1 or PD-L1 inhibitors in the HERIZON-BTC-01 trial (ESMO 2026) - No abstract available

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

Beamion BCGC-1: Four new phase Ib/II cohorts to evaluate oral zongertinib with other agents in HER2-positive metastatic breast cancer (mBC) and metastatic colorectal cancer (mCRC). (ASCO 2026) - P1/2 | "Trial details for Cohorts A–K, evaluating zongertinib as monotherapy or combined with T-DM1, T-DXd, or trastuzumab ± capecitabine in patients (pts) with HER2-positive mBC, and with T-DXd in pts with HER2-positive metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEAC), have recently been published (Hurvitz et al, Future Oncol 2025)...Here, we report 4 new cohorts (L–O) to evaluate the efficacy and safety of zongertinib plus zanidatamab in HER2-positive mBC, or plus trastuzumab or mFOLFOX6 ± trastuzumab in HER2-positive mCRC...In Ph II, the primary endpoint is OR by RECIST v1.1; secondary endpoints include PFS, disease control, AEs leading to dose reduction, PK, and pt-reported outcomes. Pts will remain on treatment until any protocol-defined stopping criterion occurs."

Metastases • New P1/2 trial • P1/2 data • Breast Cancer • Colorectal Cancer • Esophageal Adenocarcinoma • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR • HER-2

PRE-I-SPY-PI: PRE-ISPY Phase I/II Oncology Platform Program (clinicaltrials.gov) - P1/2 | N=280 | Recruiting | Sponsor: QuantumLeap Healthcare Collaborative | Phase classification: P1 ➔ P1/2 | N=124 ➔ 280 | Trial completion date: Dec 2029 ➔ Dec 2031 | Trial primary completion date: Dec 2028 ➔ Dec 2030

Biomarker • Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Breast Cancer • Cholangiocarcinoma • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

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

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

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

Health-related quality of life (HRQoL) with zanidatamab (zani) + chemotherapy (CT) ± tislelizumab (TIS) for first-line (1L) HER2-positive (HER2+) advanced/metastatic gastroesophageal adenocarcinoma (mGEA): Results from HERIZON-GEA-01 (ESMO-GI 2026) - P3 | "Background In the first interim analysis of the phase 3 HERIZON-GEA-01 trial (NCT05152147), zani + CT ± TIS significantly improved progression-free survival (PFS; >4-month prolongation of median PFS) and, with TIS, yielded a significant overall survival (OS) benefit (>7-month prolongation of median OS) vs trastuzumab (tras) + CT in 1L HER2+ mGEA. Conclusions In HERIZON-GEA-01, zani-containing regimens demonstrated clinically meaningful survival benefits while maintaining physical functioning without detriment to overall HRQoL. These data support zani + CT ± TIS in the 1L setting for pts with HER2+ mGEA."

Clinical • HEOR • Metastases • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal 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

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

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) - P2 | "No prior HER2-targeted therapy is allowed for cohort 1; prior treatment with trastuzumab deruxtecan is required for cohorts 2 and 3. This trial is open for enrollment. Originally presented at the 2025 European Society for Medical Oncology Annual Meeting."

Clinical • P2 data • Pan tumor • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Unlocking HER2 as a target in KRAS-mutated rectal cancer: a case of significant response to zanidatamab-based regimen. (PubMed, Front Immunol) - "Although the combination of chemotherapy and bevacizumab yielded promising efficacy, but tumor markers still remained high. This case underscores the potential of HER2 inhibition as an effective therapeutic strategy in KRAS-mutated CRC. It also highlights zanidatamab's promise as part of a conversion therapy approach in patients with historically refractory disease."

Biomarker • Journal • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor • HER-2 • KRAS

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

Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (mGEA): PD-L1 subgroup analysis from HERIZON-GEA-01. (ASCO 2026) - P3 | " Eligible patients (pts) with previously untreated HER2+ mGEA, irrespective of PD-L1 status, were randomized (1:1:1) to zanidatamab (1800 mg [<70 kg]/2400 mg [≥70 kg] IV Q3W) + tislelizumab (200 mg IV Q3W) + capecitabine/oxaliplatin (CAPOX) or 5-FU/cisplatin (FP); zanidatamab + CAPOX or FP; or tras + CAPOX or FP... In HERIZON-GEA-01, zanidatamab + tislelizumab + CT demonstrated meaningful improvements in PFS and OS in both PD-L1–positive and PD-L1–negative pts as determined by TAP or CPS. The longer OS observed with tras + CT in PD-L1–positive vs –negative pts may be at least partially explained by differences in subsequent therapies. These findings are notable as they demonstrate benefit for this regimen regardless of PD-L1 status."

Clinical • IO biomarker • Metastases • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2 • PD-L1

Beamion BCGC-1: Phase Ib/II Trial of Zongertinib Monotherapy/Combination Therapy - Evaluation of a Cohort of Advanced HER2-Positive Metastatic Breast Cancer (JBCS 2026) - P1/2 | "The Beamion BCGC-1 trial (NCT06324357) is a phase Ib/II trial evaluating zongertinib monotherapy or combination therapy with T-DM1, T-DXd, trastuzumab ± capecitabine, or zanidatamab in patients with HER2-positive metastatic breast cancer (mBC) and gastric cancer (GC)/colorectal cancer (CRC), with eight participating centers from Japan. The primary endpoint of Phase II is ORR (RECIST v1.1), with secondary endpoints including progression-free survival (PFS), disease control, adverse events leading to dose reduction, pharmacokinetics (PK), and patient-reported outcomes. Treatment will continue until protocol-defined discontinuation criteria are met."

Combination therapy • Metastases • Monotherapy • P1/2 data • Breast Cancer • Colorectal Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast 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

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

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