AdvanTIG-105: Phase Ib dose-expansion study of ociperlimab (OCI) + tislelizumab (TIS) with chemotherapy (chemo) in patients (pts) with metastatic squamous (sq) and non-squamous (non-sq) non-small cell lung cancer (NSCLC)

Abstract

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-naive 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-naive metastatic sq/non-sq NSCLC.