Abstract 2392
Background
Despite treatment advances, gastric cancer (GC) remains a leading cause of cancer-related death worldwide. Standard first-line chemotherapeutic regimen for advanced GC consists of fluoropyrimidine with platinum-based combinations, such as capecitabine + oxaliplatin (CAPOX). Recently, CLDN18.2 has emerged as a promising targetable biomarker. In healthy tissue, CLDN18.2 is confined to gastric mucosa tight junctions. Upon malignant transformation, cell polarity perturbations lead to exposure of CLDN18.2 on the cell surface. Zolbetuximab is a chimeric IgG1 monoclonal antibody that specifically binds to CLDN18.2 and mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. In a randomized phase II study (NCT01630083), patients (pts) with CLDN18.2+advanced GC/GEJ treated with zolbetuximab + epirubicin, oxaliplatin, and capecitabine (EOX) showed prolonged survival compared to EOX alone.
Trial design
This global, phase III, double-blind, placebo-controlled study (NCT03653507) will enroll ∼500 adult pts with CLDN18.2+/HER2– locally advanced unresectable or metastatic GC or GEJ not previously treated with chemotherapy for advanced/metastatic disease. Patients will be randomized 1:1 to receive zolbetuximab + CAPOX or placebo + CAPOX. Zolbetuximab will be administered by IV infusion as an 800 mg/m2 loading dose (Cycle 1, Day 1) followed by 600 mg/m2 Q3W in combination with CAPOX. Tumor tissue will be collected at screening to determine CLDN18.2 and HER2 status (if unknown) by central testing; pts will be considered CLDN18.2+ if ≥ 75% of tumor cells demonstrate moderate-to-strong membranous IHC staining. The primary objective is to compare progression-free survival of zolbetuximab + CAPOX vs placebo + CAPOX; secondary efficacy objectives include comparison of overall survival, objective response rate, and duration of response. The safety/tolerability profile, effects on health-related quality-of-life, PK profile, and immunogenicity of zolbetuximab are other secondary endpoints.
Clinical trial identification
NCT03653507.
Editorial acknowledgement
Patrick Tucker of OPEN Health Medical Communications.
Legal entity responsible for the study
Astellas Pharma, Inc.
Funding
Astellas Pharma, Inc.
Disclosure
J.A. Ajani: Advisory / Consultancy, Research grant / Funding (self): Astellas. S. Al-Batran: Advisory / Consultancy: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: Servier; Speaker Bureau / Expert testimony: Nordic Bioscience; Research grant / Funding (institution): Hospira; Research grant / Funding (institution): Medac; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Vifor Pharma; Research grant / Funding (self): Roche Pharma AG. Y. Bang: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Merck Serano; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Taiho; Advisory / Consultancy: Daiich-Sankyo; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): FivePrime; Research grant / Funding (institution): Curis; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Ono; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): BieGene; Advisory / Consultancy, Research grant / Funding (institution): GreenCross; Advisory / Consultancy, Research grant / Funding (institution): Genexine; Advisory / Consultancy: Samyang Biopharm; Advisory / Consultancy: Hanmi; Research grant / Funding (institution): CKD Pharma. D.V. Catenacci: Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self): Gritstone; Honoraria (self), Advisory / Consultancy: Taiho; Honoraria (self), Advisory / Consultancy: Genentech/Roche; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo. P. Enzinger: Advisory / Consultancy: Merck; Advisory / Consultancy: Astellas; Advisory / Consultancy: Celgene; Advisory / Consultancy: Lilly; Advisory / Consultancy: Loxo; Advisory / Consultancy: Taiho. D. Ilson: Advisory / Consultancy: Astellas. S. Kim: Honoraria (self): Merck. F. Lordick: Honoraria (self): Astellas; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self): AstraZeneca; Advisory / Consultancy: Biontech; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self): Elsevier; Travel / Accommodation / Expenses: Infomedica; Honoraria (self): Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self): Servier; Honoraria (self): Amgen; Honoraria (self): Nordic Group; Honoraria (self): Ganymed Pharma; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Fresenius Biotech; Travel / Accommodation / Expenses: Taiho Pharma. K. Shitara: Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy: BMS; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (institution): Novartis; Honoraria (institution): AbbVie; Honoraria (institution): Yakult; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Chugai pharma; Advisory / Consultancy, Research grant / Funding (institution): MSD; Research grant / Funding (institution): Medi Science. E. Van Cutsem: Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: Incyte; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Merck Sharp & Dohme; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Research grant / Funding (institution): Amgen. A. Arozullah: Full / Part-time employment: Astellas Pharma Global Development. J.W. Park: Full / Part-time employment: Astellas Pharma Global Development. All other authors have declared no conflicts of interest.
Resources from the same session
3392 - Post-hoc analysis of the nintedanib exposure-response relationships in the CHIVA trial in advanced ovarian cancer: (a GINECO study)
Presenter: Skerdi HAVIARI
Session: Poster Display session 2
Resources:
Abstract
714 - The feasibility and efficacy of gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian insufficiency in patient with malignant ovarian germ cell tumors
Presenter: Min Kyu Kim
Session: Poster Display session 2
Resources:
Abstract
1753 - Ex vivo cytotoxicity and in vivo antitumor activity of a novel highly selective STAT3 inhibitor YHO-1701 for ovarian and endometrial cancer
Presenter: Kosei Hasegawa
Session: Poster Display session 2
Resources:
Abstract
3739 - Mutational landscapes and tumor mutational burden expression in endometrial cancer
Presenter: Yingli Zhang
Session: Poster Display session 2
Resources:
Abstract
2109 - Clinical features and frequency of mismatch repair protein deficiency in ovarian clear cell and endometrioid carcinoma patients.
Presenter: Kazuhiro Takehara
Session: Poster Display session 2
Resources:
Abstract
4554 - Prospective study evaluating white adipose tissue inflammation and clinicopathologic features in endometrial cancer
Presenter: Lea Moukarzel
Session: Poster Display session 2
Resources:
Abstract
3645 - Cancer-specific survival with or without adjuvant chemotherapy in high-risk stage I endometrial cancer
Presenter: Jenny Ko
Session: Poster Display session 2
Resources:
Abstract
3394 - Pembrolizumab in Patients with MSI-H Advanced Endometrial Cancer from the KEYNOTE-158 Study
Presenter: David Omalley
Session: Poster Display session 2
Resources:
Abstract
3388 - Who drops out of cervical cancer screening? Results from the EDIFICE 6 survey
Presenter: Thibault de La Motte Rouge
Session: Poster Display session 2
Resources:
Abstract
2485 - Identification of a RNA-Seq Based Signature to Improve Prognostic for Uterine Sarcoma
Presenter: Jian-Guo Zhou
Session: Poster Display session 2
Resources:
Abstract