Abstract 261TiP
Background
HER2-expressing (immunohistochemistry [IHC] 3+/2+) BTC has a poor prognosis. First-line gemcitabine, cisplatin, and immunotherapy has demonstrated clinical benefit in LA/m BTC and is SOC in this setting; however, outcomes need to be further improved. T-DXd is a HER2-directed antibody-drug conjugate that has shown clinically meaningful antitumor activity in pretreated patients with LA/m BTC, as shown in the Phase II HERB study and BTC cohort of the Phase II DESTINY-PanTumor02 study. Here, we describe DESTINY-BTC01, evaluating first-line T-DXd with rilvegostomig (a bispecific, humanized immunoglobulin G1 antibody targeting programmed cell death 1 and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitor motif domains) vs SOC in patients with HER2-expressing LA/m BTC.
Trial design
DESTINY-BTC01 (NCT06467357) is a randomized, open-label, multicenter, Phase 3 study in patients with histologically confirmed HER2-expressing (IHC 3+/2+), unresectable, previously untreated LA/m BTC. Prior perioperative and/or adjuvant treatment is permitted if >6 months between end of adjuvant treatment and diagnosis of LA/m disease. A safety run-in will evaluate the safety and tolerability of T-DXd with rilvegostomig, prior to randomization of patients to 3 arms: T-DXd with rilvegostomig; T-DXd alone; or gemcitabine, cisplatin, and durvalumab. The primary efficacy endpoint is overall survival (OS) in the HER2 IHC 3+ population receiving T-DXd with rilvegostomig vs SOC. Key secondary endpoints are OS in the HER2 IHC 3+/2+ population receiving T-DXd with rilvegostomig vs SOC, and the HER2 IHC 3+ and IHC 3+/2+ populations receiving T-DXd monotherapy vs SOC. Other secondary endpoints include objective response rate (per Response Evaluation Criteria in Solid Tumours version 1.1), duration of response, and progression-free survival in the IHC 3+ and IHC 3+/2+ populations receiving T-DXd with or without rilvegostomig vs SOC. Safety and tolerability will also be assessed. Enrollment is ongoing, with a recruitment target of 620 patients.
Clinical trial identification
NCT06467357.
Legal entity responsible for the study
AstraZeneca and Daiichi Sankyo.
Funding
This study is sponsored by AstraZeneca. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201).
Disclosure
M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eisai, Nihon Servier, Novartis, Bristol Myers Squibb, MSD, Boehringer Ingelheim, Astellas Pharma, GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Eli Lilly Japan, Eisai, Nihon Servier, Novartis, Taiho, Yakult, Teijin Pharma, AbbVie, Fujifilm Toyama Chemical, Incyte Biosciences Japan, Takeda, Ono, MSD, Taisho Pharmaceutical, Nippon Kayaku, Guardant Health Japan, Nobelpharma, EA Pharma; Financial Interests, Institutional, Coordinating PI: Bayer, Bristol Myers Squibb, Eisai, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, MSD, Ono, Novartis, J-Pharma, Chiome Bioscience, Nihon Servier, Delta-Fly Pharma, Syneos Health, Merus.N.V., Merck biopharma, Boehringer Ingelheim, Invitae, Nobelpharma; Financial Interests, Personal, Steering Committee Member: Chugai, Nihon Servier, Takeda, Novartis, Eisai, Rakuten Medical. 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, Alligator Bioscience AB; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. G. Cohen: Financial Interests, Personal, Full or part-time Employment, I am a full time employee of AstraZeneca. Position is Global Clinical Lead in Immuno-oncology: AstraZeneca; Financial Interests, Personal, Stocks/Shares, Own stock in the company as an employee: AstraZeneca. S. Raoufmoghaddam: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Winter: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. All other authors have declared no conflicts of interest.