1423P - 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

Background

In an ongoing phase 2 trial, zanidatamab (zani), a HER2-targeted bispecific antibody + chemotherapy (chemo) showed encouraging antitumour activity with a manageable safety profile in the 1L treatment of patients (pts) with HER2+ mGEA (prior data cut-off: Oct 2022). Here, we report new and updated results, including the latest overall survival (OS) data.

Methods

In this open-label phase 2 trial (NCT03929666), eligible pts (≥18 years with HER2-expressing mGEA) were treated with zani + physician’s choice of chemo (mFOLFOX6, CAPOX or FP). After the first 25 pts were enrolled, pretreatment with antidiarrhoeal prophylaxis was added for cycle 1. Endpoints included confirmed objective response rate (cORR), duration of response (DoR), progression-free survival (PFS), OS and rate/severity of adverse events (AEs).

Results

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%]). The median follow-up was 41.5 (range, 23.0-52.7) months; treatment was ongoing for 10 pts (22%) with 24 (52%) still on study. Among 37 response-evaluable pts with ccHER2+ mGEA, the cORR was 84% (95% CI: 68, 94); 4 achieved complete responses. The median DoR was 18.7 (95% CI: 8.3, not reached) months. Among all pts with ccHER2+ mGEA, the median PFS was 15.2 (95% CI: 9.5, 33.4) months. While median OS was not mature, the Kaplan-Meier–estimated 24-month OS was 65% (95% CI: 48, 78) and 30-month OS was 59% (95% CI: 41, 73). Grade ≥3 treatment-related AEs (TRAEs) occurring in ≥5% of all 46 pts enrolled in this study were diarrhoea (35%), hypokalaemia (22%), nausea (7%) and vomiting (7%). Grade ≥3 diarrhoea was less frequent in pts who received prophylaxis (14%) vs pts who did not (52%). Eight (17%) pts had serious TRAEs; there were no treatment-related deaths.

Conclusions

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 trial identification

NCT03929666.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Evelyn Huang, PhD, of CMC Affinity.

Legal entity responsible for the study

Jazz Pharmaceuticals.

Funding

Jazz Pharmaceuticals.

Disclosure

E. Elimova: Financial Interests, Personal, Invited Speaker: Roche, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: BeiGene, Signatera, AbbVie, Astellas, Viracta Tx; Financial Interests, Institutional, Steering Committee Member, Institution receives: Jazz; Financial Interests, Institutional, Local PI: Jazz, Zymeworks, Amgen, AstraZeneca, BMS, Trio-Oncology; Other, A family member employed by Merck Vaccines: Merck. J.A. Ajani: Financial Interests, Personal, Advisory Board: Acrotech Biopharma, Aduro Biotech, Amgen, Astellas Pharma, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, DAVA Pharmaceuticals, Eli Lilly, Fresenius Kabi, Gilead Sciences, Grail, Merck, Novartis, Oncotherics, Servier, Zymeworks; Financial Interests, Personal, Advisory Role: American Cancer Society, Amgen, Arcus Biosciences, Astellas Pharma, BeiGene, Bristol Myers Squibb, Geneos, Gilead Sciences, Insys Therapeutics, Merck, Novartis, Servier, Vaccinogen; Financial Interests, Research Funding: Amgen, Astellas Pharma (Inst), Bristol Myers Squibb, Daiichi Sankyo, Delta-Fly Pharma, Gilead Sciences, Lilly/ImClone, MedImmune, Merck, Novartis, ProLynx, Roche/Genentech, Taiho Pharmaceutical, Takeda, Zymeworks. H.A. Burris: Financial Interests, Institutional, Other, Consulting: AstraZeneca, Grail, Incyte, Roche, Vincerx Pharma; Financial Interests, Personal, Stocks/Shares: HCA Healthcare; Financial Interests, Institutional, Local PI: AbbVie, Agios, Arch Oncology, ARMO Biosciences, Array BioPharma, Arvinas, AstraZeneca, Bayer, BeiGene, BioAtla, BioMed Valley Discoveries, BioTheryX, Boehringer Ingelheim, Bristol Myers Squibb, CALGB, CicloMed, Coordination Pharmaceuticals, CytomX, eFFECTOR Therapeutics, Lilly, EMD Serono, Roche/Genentech, Gilead Sciences, GSK, Gossamer Bio, Harpoon Therapeutics, Hengrui Therapeutics, Incyte, Janssen, Jounce Therapeutics, Kymab, MacroGenics, MedImmune, Merck, Millennium/Takeda, Moderna, NGM Biopharmaceuticals, Novartis, Pfizer, Revolution Medicines, Ryvu Therapeutics, Foundation Medicine, Seagen, Tesaro, TG Therapeutics, Verastem, Vertex Pharmaceuticals, XBiotech, Zymeworks; Financial Interests, Institutional, Funding: Celgene; Non-Financial Interests, Other, Consulting: Bristol Myers Squibb, Novartis. C.S. Denlinger: Financial Interests, Personal, Research Funding: Eli Lilly & Co.; Financial Interests, Personal, Other, data safety monitoring board: Zymeworks; Financial Interests, Personal, Full or part-time Employment: National Comprehensive Cancer Network. S. Iqbal: Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas Pharma, AstraZeneca, BeiGene, Exelixis, Merck, Astellas Pharma; Financial Interests, Personal, Research Funding: Amgen, Aslan Pharmaceuticals, Astellas Pharma, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Indivumed, MSD Oncology, Roche/Genentech, SillaJen, Zymeworks. Y. Kang: Financial Interests, Personal, Advisory Board: ALX Oncology, Zymeworks, Amgen, Novartis, Macrogenics, Daehwa, Blueprint, Surface Oncology, BMS, Merck, Roche, Liscure. K. Lee: Financial Interests, Personal, Advisory Board: AbbVie, Astellas, BMS (Korea), Daiichi Sankyo (Korea), Merck Sharp & Dohme (Korea), MetaFines; Financial Interests, Personal, Invited Speaker: Bayer (Korea), Merck KGaA (Korea); Financial Interests, Institutional, Local PI, For conducting clinical trials: ALX Oncology, Amgen, Arcus Biosciences, Astellas Pharma, AstraZeneca, BeiGene, Bolt Therapeutics, Daiichi Sankyo, Elevar, Erasca, Inc., Exelixis, Genome & Company, GSK, IgM Biosciences, InventisBio, Jazz Pharmaceuticals, Leap Therapeutics, Macrogenics, MedPacto, Medicenna, Merck KGaA, Merck Sharp & Dohme, MetaFines, Ono Pharmaceutical, Panolos Bioscience, Pfizer, Seagen, TRIO Oncology, Taiho Pharmaceutical, Trishula Therapeutics, Wellmarker Bio, Y-Biologics; Non-Financial Interests, Leadership Role, SMC chair of ASPEN-06 study: ALX Oncology. B. Lin: Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Other, Clinical research institutional support: Exelixis, Jazz Pharmaceuticals, Incyte, Relay Therapeutics, Merck, Tvardi Therapeutics, Genentech/Roche, Pfizer/Cardiff Oncology. R. Mehta: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bristol Myers Squibb, BostonGene, Eli Lilly, GSK, Guardant Health, Merck, Novartis, Seagen; Financial Interests, Personal, Speaker, Consultant, Advisor: Eli Lilly; Financial Interests, Personal, Other, serves on the DSMB: Arcus Biosciences. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, Aslan, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA, MSD, LG Chem, Astellas, AbbVie, J-Pharma, Mirati Therapeutics, Eutilex, Moderna, Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, Amgen, LG Biochemical, Astellas, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: MSD, Daiichi Sankyo; Financial Interests, Personal, Steering Committee Member: Amgen; Financial Interests, Institutional, Funding: MSD, Lilly; Financial Interests, Institutional, Research Grant: BMS, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Indivumed, AstraZeneca; Financial Interests, Other, Drug supply for clinical trial: Merck; Financial Interests, Institutional, Coordinating PI, Drug supply for clinical trial: MSD; Financial Interests, Institutional, Local PI, drug supply for clinical trial: Zymeworks; Financial Interests, Institutional, Local PI, drug supply for clinical trial: BeiGene; Financial Interests, Local PI: Roche. C. Xie, P. Garfin: Financial Interests, Personal, Full or part-time Employment: Jazz Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Jazz Pharmaceuticals. G.Y. Ku: Financial Interests, Personal, Research Funding: AstraZeneca, BMS, CARsgen, Daiichi Sankyo, I-MAB, Jazz Pharmaceuticals, Merck, Oncolys, Pieris, Triumvira, Zymeworks; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting: Astellas, AstraZeneca, Bayer, BMS, Daiichi Sankyo, I-MAB, Jazz Pharmaceuticals, Merck, Pieris, Zymeworks; Financial Interests, Personal, Other, Travel support: Dava Oncology, I-MAB. All other authors have declared no conflicts of interest.