Abstract 148P
Background
T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) inhibitor with an anti-programmed cell death protein 1 (PD-1) antibody is a promising combination showing antitumor activity in solid tumors. Phase 1/1b open-label study AdvanTIG-105 assessed safety and preliminary antitumor activity of anti-TIGIT monoclonal antibody (mAb) OCI + anti-PD-1 mAb TIS in pts with advanced unresectable solid tumors (NCT04047862). In dose-escalation, OCI + TIS was well tolerated showing preliminary antitumor activity, establishing the recommended phase 2 dose (RP2D) of OCI 900mg IV every 3 weeks (Q3W) plus TIS 200mg IV Q3W. We report dose-expansion results in pts with ES-SCLC.
Methods
Eligible adults had histologically/cytologically confirmed ES-SCLC and had received no prior systemic therapies. Pts received RP2D of OCI + TIS with cisplatin or carboplatin + etoposide Q3W for 4 cycles, followed by RP2D OCI + TIS Q3W until disease progression, intolerable toxicity, or withdrawal of consent. Primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), duration of response (DoR), and safety.
Results
As of June 20, 2022, 42 pts were enrolled, of which 40 were efficacy evaluable; median study follow-up time was 24.9 weeks (range 3.0-67.9). Confirmed ORR was 65.0% (95% confidence interval [CI]: 48.3, 79.4) and median DoR was 4.3 months (95% CI: 3.2, 5.6). Median PFS was 4.9 months (95% CI: 4.2, 5.7) with a 6-month PFS rate of 27.3%. All 42 pts experienced at least 1 treatment-emergent adverse event (TEAE); 25 (59.5%) had Grade ≥ 3 TEAEs and 17 (40.5%) had serious TEAEs. Most common TEAEs were neutrophil count decreased and anemia (54.8% each). Immune-mediated TEAEs were reported in 12 pts (28.6%) and TEAEs led to treatment discontinuation in two pts. Pneumonia (unrelated to treatment) and disease progression led to death in two pts.
Conclusions
OCI 900mg + TIS 200mg with cisplatin/carboplatin plus etoposide was generally well tolerated and showed antitumor activity in pts with ES-SCLC.
Clinical trial identification
NCT04047862.
Editorial acknowledgement
This study was sponsored by BeiGene, Ltd. Medical writing support, under the direction of the authors, was provided by Sophie Cook, PhD, of Ashfield MedComms, an Inizio company, and was funded by BeiGene, Ltd. The authors would like to thank Rang Gao and Ruihua Wang for their contributions.
Legal entity responsible for the study
BeiGene, Ltd.
Funding
BeiGene, Ltd.
Disclosure
J. Zhang: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Biodesix, BMS, Cardinal Health, Daiichi Sankyo, Hengrui, Eli Lilly, Mirati, Nexus Health, Novocure, Sanofi, Takeda Oncology; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, MJH Life Sciences, Novartis, Regeneron, Sanofi; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Genentech, Mirati, Nilogen; Financial Interests, Institutional, Funding: AbbVie, BeiGene, Hengrui, InnoCare Pharma, Merck, Mirati, Novartis; Financial Interests, Institutional, Principal Investigator: AbbVie, BeiGene, Hengrui, InnoCare Pharma, Merck, Mirati, Novartis; Financial Interests, Institutional, Sponsor/Funding: AbbVie, BeiGene, Hengrui, InnoCare Pharma, Merck, Mirati, Novartis. M. Hussein: Financial Interests, Personal, Advisory Board: Integra Connect, Coherus Biosciences, Karyopham Therapeutics, BMS, AstraZeneca, Mirati Therapeutics, Exelixis, Biopharma, AbbVie, Oncotype, Aptitude Helth; Financial Interests, Personal, Advisory Role: Karyopham Therapeutics, BMS, AstraZeneca, Mirati Therapeutics, Exelixis, Biopharma, AbbVie, Oncotype, Aptitude Helth. S.C. Kao: Financial Interests, Personal and Institutional, Advisory Board: AZ, Pfizer, Boeringher, Takeda, MSD, BMS, Roche, Specialised Therapeutics; Financial Interests, Personal and Institutional, Other, Honoraria: AZ, Pfizer, Boeringher, Takeda, MSD, BMS, Roche, Specialised Therapeutics; Financial Interests, Personal, Funding: AstraZeneca. T.D. Clay: Financial Interests, Personal, Other, Honoraria: Specialised Therapeutics Australia; Financial Interests, Personal, Advisory Board: AstraZeneca, Foundation Medicine; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Writing Engagements: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Principal Investigator: Pfizer, BMS, Amgen, Daiichi Sankyo, AbbVie, Beigene, Immutep, Clovis, Janssen; Financial Interests, Institutional, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Travel / Accommodation Expenses: Astellas. G. Chang: Financial Interests, Personal, Other, Honoraria: F. Hoffmann–La Roche, Ltd, Eli Lilly and Company Oncology, AstraZeneca, Novartis, Pfizer, Boehringer Ingelheim, Bristol Myers Squibb, and Merck Sharp & Dohme. H. Zheng: Financial Interests, Institutional, Full or part-time Employment: BeiGene USA; Financial Interests, Institutional, Stocks/Shares: BeiGene USA. W. Tan: Financial Interests, Institutional, Full or part-time Employment: BeiGene, Ltd. All other authors have declared no conflicts of interest.