Abstract 1017P
Background
T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) inhibitor + an anti-programmed cell death protein 1 (PD-1) antibody is a promising combination which shows potent efficacy in solid tumors. AdvanTIG-105 is a Phase 1/1b open-label study designed to assess the safety and preliminary antitumor activity of OCI, an anti-TIGIT monoclonal antibody (mAb), + TIS, an anti-PD-1 mAb, in pts with metastatic unresectable solid tumors (NCT04047862). In the dose-escalation part, OCI + TIS was well tolerated, preliminary efficacy was observed, and the recommended Phase 2 dose (RP2D) of OCI 900 mg intravenous (IV) every three weeks (Q3W) + TIS 200 mg IV Q3W was established. We report results from the dose-expansion (Cohorts 1 [C1] & 2 [C2]) of the AdvanTIG-105 study.
Methods
Treatment-naïve adult pts with histologically/cytologically confirmed metastatic sq (C1) or non-sq with EGFR/ALK/ROS-1 wild-type tumors (C2) NSCLC were enrolled. Pts in C1 received the RP2D of OCI + TIS with paclitaxel/nab-paclitaxel + carboplatin and pts in C2 received the RP2D of OCI + TIS with pemetrexed + cisplatin/carboplatin, both until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included safety.
Results
As of March 18, 2022, 84 pts were enrolled (C1: n=41; C2: n=43). The median study follow-up was 17.7 weeks (range 1.1–42.6) in C1 and 15.0 weeks (3.0–51.1) in C2. Of the 76 efficacy-evaluable pts, the confirmed ORR in C1 was 45.9% (95% confidence interval [CI]: 0.3, 0.6) and 25.6% (95% CI: 0.1, 0.4) in C2. In total, 81 pts (96.4%) experienced ≥ 1 treatment-emergent adverse event (TEAE), and 48 pts (57.1%) had ≥ Grade 3 TEAEs. Serious TEAEs occurred in 26 pts (31.0%). The most common TEAEs were anemia (41.7%), neutrophil count decreased (33.3%), and white blood cell count decreased (33.3%).
Conclusions
The RP2D of OCI 900 mg IV Q3W and TIS 200 mg IV Q3W + chemo was generally well tolerated and showed antitumor activity in pts with treatment-naïve metastatic sq/non-sq NSCLC. Prof. Y. Yu and Prof. D. Huang have contributed equally to the study.
Clinical trial identification
NCT04047862.
Editorial acknowledgement
Medical writing support, under the direction of the authors, was provided by Victoria Dagwell, MSc, and Helena Crisford, MSc, of Ashfield MedComms, an Ashfield Health company, and was funded by BeiGene, Ltd.
Legal entity responsible for the study
BeiGene, Ltd.
Funding
BeiGene, Ltd.
Disclosure
S. Kao: Financial Interests, Invited Speaker: Roche, MSD, BMS, Pfizer, AZ, Specialised Therapeutic; Financial Interests, Advisory Board: Takeda, Pfizer, Roche, Boehringer, Lilly, MSD, Specialised Therapeutics; Financial Interests, Research Grant: AZ. W. Xu: Financial Interests, Invited Speaker: Merck, MSD, AZD; Financial Interests, Advisory Board: MSD, Merck, Novartis; Financial Interests, Research Grant: Merck. J. Kim: Financial Interests, Expert Testimony: CJ Healthcare; Financial Interests, Member of the Board of Directors: IMBdx; Financial Interests, Research Grant: AstraZeneca, Boehringer Ingelheim, Sanofi, Lilly, CJ Healthcare, Ono Pharmaceutical, Pfizer, Novotech, Astellas Pharma, Merck, Alpha Biopharma, Yuhan, MSD, IL-Yang Pharm; Financial Interests, Advisory Role: CJ HealthcareAbion Inc. R. Wang: Financial Interests, Full or part-time Employment: BeiGene, Ltd. H. Zheng: Financial Interests, Full or part-time Employment: BeiGene USA; Financial Interests, Stocks/Shares: BeiGene USA. W. Tan: Financial Interests, Full or part-time Employment: BeiGene, Ltd.; Financial Interests, Stocks/Shares: BeiGene, Ltd. R. Gao: Financial Interests, Full or part-time Employment: BeiGene, Ltd. S. Lu: Financial Interests, Invited Speaker: AstraZeneca, Roche, Hansoh; Financial Interests, Advisory Board: AstraZeneca, Pfizer, Hutchison MediPharma, ZaiLab, GenomiCare, Yuhan Corporation, Menarini, InventisBio Co. Ltd., Mirati Therapeutics Inc, Roche; Financial Interests, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui BeiGene and Roche, Hansoh; Financial Interests, Principal Investigator: AstraZeneca, Hutchison, Heng Rui BeiGene and Roche, Hansoh. All other authors have declared no conflicts of interest.