Abstract 495TiP
Background
GC/GEJC is the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death worldwide (Sung H, et al. CA Cancer J Clin 2021). Prognosis is poor in GC/GEJC; median overall survival (OS) is less than 10 months in the 2L setting and less than 6 months in the 3L+ setting (Wilke H, et al. Lancet Oncol 2014; Shitara K, et al. Lancet Oncol 2018). New treatment options are needed. CLDN18.2 has emerged as a new therapeutic target in GC/GEJC. AZD0901, a potential first-in-class CLDN18.2-targeted antibody conjugated to monomethyl auristatin E via a protease cleavable linker, has demonstrated clinical activity in a phase 1 study in advanced GC/GEJC (Xu RH, et al. J Clin Oncol 2023). CLARITY-Gastric 01 (NCT06346392) is a randomised, open-label, sponsor-blinded, global phase 3 study that will assess the efficacy and safety of AZD0901 vs investigator’s (INV) choice of therapy after ≥1 prior therapy for advanced GC/GEJC expressing CLDN18.2.
Trial design
Participants (pts) will be randomised to AZD0901 dose level 1 intravenous (IV) every three weeks (Q3W), AZD0901 dose level 2 IV Q3W or INV choice of therapy (2L: ramucirumab [ram] + paclitaxel [PTX], PTX or docetaxel [for pts with contraindication to ram only]; 3L+: irinotecan, TAS-102 [excluding China] or apatinib [China only]). Eligible pts must have histologically-confirmed, unresectable, locally advanced or metastatic GC/GEJC (non-HER2+, CLDN18.2 expression). Pts must have disease progression on/after ≥1 prior regimen (including platinum-fluoropyrimidine) and have an ECOG performance status of 0 or 1. Pts previously treated with CLDN18.2-targeting therapy (other than naked monoclonal antibody) are excluded. Recruitment has begun and pts are planned to be enrolled at 175 study sites across Asia, Europe and North America. Dual primary endpoints are progression-free survival (PFS; intent-to-treat [ITT] pts) and OS (3L+ pts). The secondary endpoints include OS (ITT pts), PFS (3L+ pts), objective response rate and duration of response (ITT and 3L+ pts), and safety/tolerability.
Clinical trial identification
NCT06346392.
Editorial acknowledgement
Medical writing support, under the direction of the authors, was provided by Eilidh McLachlan, PhD, on behalf of CMC Connect, a division of IPG Health Medical Communications, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
K. Shitara: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Takeda, Ono Pharmaceutical, MSD, Novartis, Daiichi Sankyo, Amgen, Guardant Health Japan Corp, Astellas Pharma Inc., Astellas, Bayer, AstraZeneca, Zymeworks Biopharmaceuticals Inc., ALX Oncology Inc; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Janssen, AstraZeneca, Eli Lilly, Astellas, Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Astellas, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, MSD, Eisai, Amgen, PRA Health Sciences. Y.Y. Janjigian: Financial Interests, Personal, Advisory Board: AbbVie, Arcus Biosciences, Ask- Gene Pharma, Inc., AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Inc., Eli Lilly, GSK, Guardant Health, Inc., Imugene, Lynx Health, Merck, Sanofi Genzyme, Seagen, Zymeworks Inc.; Financial Interests, Personal, Other, Consulting: Amerisource Bergen, Astellas, Basilea Pharmaceutica, Geneos Therapeutics, Imedex, Inspirna, Mersana Therapeutics, Paradigm Medical Communications, Pfizer, Silverback Therapeutics; Financial Interests, Personal, Other, Consulting and Invited Speaker: Arcus Biosciences, AstraZeneca, Clinical Care Options, HMP Education, Merck Serono, PeerView Institute, Research to Practice; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Ed MedResources (OncInfo), H.C. Wainwright & Co., LLC, Merck, TotalCME, AstraZeneca, Transcenta Holding Limited; Financial Interests, Personal, Other, Consulting, Invited Speaker and Chair of Giants of Cancer Care Steering Committee: Michael J. Hennessy Associates; Financial Interests, Personal, Other, Consulting and Moderator: Physicians' Education Resource, LLC; Financial Interests, Personal, Stocks/Shares, Stock option: Inspirna; Financial Interests, Personal and Institutional, Research Grant: NCI, Department of Defense, Cycle for Survival, Fred's Team, Inspirna, Bayer, Genentech/Roche, Bristol Myers Squibb, Eli Lilly, Merck, Transcenta, Stand Up To Cancer, AstraZeneca, Arcus Biosciences. E. Elimova: Financial Interests, Personal, Invited Speaker: Roche, Daiichi; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: BeiGene, Signatera, AbbVie, Astellas, Viracta Tx; Financial Interests, Institutional, Invited Speaker, Institution receives: Jazz; Financial Interests, Institutional, Invited Speaker: Jazz, Zymeworks, Amgen, AstraZeneca, BMS; Other, A family member employed by Merck Vaccines: Merck. J. Zhang: Financial Interests, Personal, Invited Speaker: Roche, HengRui Pharmacy, MSD; Financial Interests, Personal, Expert Testimony: AstraZeneca. M. Chen: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Roche; Financial Interests, Personal, Advisory Board: ONO, Astellas, Eli Lilly, TTY; Financial Interests, Personal and Institutional, Invited Speaker: Roche, MSD, Amgen, AstraZeneca, Ono; Financial Interests, Personal and Institutional, Research Grant: Boehringer Ingelheim; Non-Financial Interests, Personal, Product Samples: Eli Lilly. E. Smyth: Financial Interests, Personal, Invited Speaker: Amgen, Bristol Myers Squibb, Imedex, Merck, Novartis, Prova Education, Servier, TouchIME, Elsevier, Peervoice, Cor2Ed, Daiichi Sankyo, MSD, Suzhou Liangihui Network Technology Company Ltd.; Financial Interests, Personal, Other, TSC: Amgen; Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bristol Myers Squibb, My Personal Therapeutics, Novartis, Roche, Servier, Zymeworks, Viracta, Boehringer Ingelheim, AbbVie, Natera; Financial Interests, Personal, Other, IDMC: BeiGene, Zymeworks; Financial Interests, Personal, Expert Testimony: Bristol Myers Squibb; Financial Interests, Personal, Other, IDMC chair: Everest Clinical Research; Financial Interests, Personal, Other, IDMC Chair: Jazz Pharmaceuticals; Financial Interests, Personal, Officer: EORTC GI Clinical Trials Group; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Roche, AstraZeneca, Merus, Basilea, MSD, Amgen, Mirati; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, AstraZeneca; Non-Financial Interests, Leadership Role, Trustee: UK & Ireland Oesophagogastric Group (UKIOG). R. Miao: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. S. Liu: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. M. Holmblad: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. R. Xu: Financial Interests, Personal, Invited Speaker: BMS, MSD, Hutchison Pharm; Financial Interests, Personal, Advisory Board: Henrui, BeiGene, Astellas, Merck, Junshi, Innovent, Keymed Biosience. All other authors have declared no conflicts of interest.