1533P - Advantig-105: Phase Ib dose-expansion study of ociperlimab (OCI) + tislelizumab (TIS) with chemotherapy (CT) in patients (pts) with metastatic oesophageal squamous cell carcinoma (ESCC) and oesophageal adenocarcinoma (EAC)

Background

A T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) inhibitor + an anti-PD-1 antibody is a promising combination which shows potent efficacy in solid tumors. AdvanTIG-105 (NCT04047862) is a phase I/1b open-label study designed to assess the safety and preliminary antitumor activity of anti-TIGIT mAb OCI + anti-PD-1 mAb TIS in pts with metastatic unresectable solid tumors. OCI + TIS was well tolerated in the dose-escalation part, preliminary efficacy was observed, and the recommended phase II dose (RP2D) of OCI 900 mg IV Q3W + TIS 200 mg IV Q3W was established. Here we report results from dose-expansion cohorts 6 (C6) and 7 (C7).

Methods

Treatment-naïve adult pts with histologically/cytologically confirmed metastatic ESCC (C6) or EAC (C7) were enrolled. Pts received the RP2D of OCI + TIS with cisplatin + 5-fluorouracil/paclitaxel until disease progression, intolerable toxicity, or consent withdrawal. Primary endpoint: investigator-assessed ORR per RECIST v1.1. Secondary endpoints: efficacy (PFS, DoR, DCR), safety and PD-L1 and TIGIT expression as predictive efficacy biomarkers.

Results

As of Feb 2, 2023, 27 pts (C6: n=21; C7: n=6) with a median age of 63.0 y (range C6: 51-72; C7: 58-69) were enrolled; 24 (C6: n=19; C7: n=5) were efficacy evaluable. Efficacy and safety data are summarized in the table. ORRs by biomarker subgroups: C6, 100% in pts with PD-L1 tumor area positivity (TAP) score ≥10% (n=4) vs 76.9% in pts with PD-L1 TAP <10% (n=13); 80.0% in pts with TIGIT IC score ≥5% (n=10) vs 87.5% in pts with TIGIT IC <5% (n=8). C7 had too few pts for biomarker subgroup analysis.

Table: 1533P

Efficacy and Safety Summary

DCR, disease control rate; DoR, duration of response; imAE, immune-mediate adverse event; mo, months; NE, not estimable; ORR, objective response rate; PFS, progression-free survival; TEAE, treatment-emergent adverse event.

Conclusions

These results demonstrate that OCI 900 mg + TIS 200 mg + CT had a safety profile consistent with previous reports and showed encouraging antitumor activity in pts with stage IV ESCC and EAC.

Clinical trial identification

NCT04047862.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Apurva Davé, PhD, of MedicalExpressions, an Inizio company, and was funded by BeiGene, Ltd.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

D.R. Spigel: Financial Interests, Personal, Research Funding: AbbVie, Aeglea Biotherapeutics, Agios, Amgen, AnHeart Therapeutics, Apollomics, Arcus, Arrys Therapeutics, Ascendis Pharma, Astellas, AstraZeneca, Bayer, BeiGene, BIND Therapeutics, BioNTech RNA Pharmaceuticals, Blueprint Medicine, Boehringer Ingelheim, Bristol Myers Squibb, Calithera, Celgene, Celldex, Clovis, Cyteir Therapeutics, Daiichi Sankyo, Denovo Biopharma, Eisai, Elevation Oncology, Endeavor, Erasca, Faeth Therapeutics, FujiFilm Pharmaceuticals, G1 Therapeutics, Roche/Genentech, Gilead Sciences, GSK, GRAIL, Hutchison medipharma, ImClone Systems, Incyte, Ipsen, Janssen, Jazz Pharmaceuticals, Kronos Bio, Lilly, Loxo Oncology, Lyell Immunopharma, MacroGenics, MedImmune, Merck, Millennium Pharmaceuticals, Moderna, Molecular Template, Monte Rosa Therapeutics, Nektar, Neon Therapeutics, Novartis, Novocure, Peloton Therapeutics, PureTech Health, Razor Genomics, Repare Therapeutics, Rgenix, Seagen, Shenzhen Chipscreen Biosciences, Stemline Therapeutics, Synthekine, Taiho, Tango Therapeutics, Tarveda, Tesaro, Tizona Therapeutics, Transgene, UT Southwestern, Verastem, Zai Laboratory; Financial Interests, Personal, Advisory Role: AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Evidera, GSK, Ipsen Biopharmaceuticals, Janssen, Jazz Pharmaceuticals, Lilly, Molecular Templates, Monte Rosa Therapeutics, Novartis, Novocure, Pfizer, Regeneron Pharmaceuticals, Roche/Genentech, Sanofi-Aventis. H.H. Yoon: Financial Interests, Personal, Speaker, Consultant, Advisor: ALX Oncology, AstraZeneca, BeiGene, Bristol Myer Squibb, MacroGenics, Merck, OncXerna, Zymeworks, Novartis, Amgen; Financial Interests, Personal, Expert Testimony: MJH Life Sciences; Financial Interests, Personal, Other, Honoraria: MJH Life Sciences, Elevation Oncology, Astellas; Financial Interests, Personal, Other, travel, accommodations expenses: BeiGene, Elevation Oncology, Prime, Astellas; Financial Interests, Personal, Research Funding: Merck, Amgen, Bristol Myer Squibb, CARsgen Therapeutics. E.S. Ahern: Financial Interests, Personal, Research Funding: Amgen. H. Zheng; W. Tan; Z. Zhou; Financial Interests, Personal, Full or part-time Employment: BeiGene (Shanghai) Co., Ltd. R. Wang: Financial Interests, Personal, Full or part-time Employment: BeiGene (Shanghai) Co., Ltd; Financial Interests, Personal, Ownership Interest: BeiGene (Shanghai) Co., Ltd. All other authors have declared no conflicts of interest.