Aims: 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 has shown promising antitumor activity in solid tumors. Phase 1/1b open-label study AdvanTIG-105 (NCT04047862) assessed safety and preliminary antitumor activity of anti-TIGIT monoclonal antibody (mAb) ociperlimab + anti-PD-1 mAb tislelizumab in patients with advanced solid tumors. During dose-escalation, ociperlimab + tislelizumab was well tolerated, showing antitumor activity, establishing the recommended phase 2 dose (RP2D) of ociperlimab 900mg IV Q3W + tislelizumab 200mg IV Q3W. Here, we report Cohort 5 dose-expansion results.
Methods: Eligible adults had histologically/cytologically confirmed locally advanced or metastatic CPI-experienced NSCLC for which they received ≤2 prior therapies, including anti-PD-(L)1 in the most recent line, and progressed after complete or partial response or stable disease. Patients received RP2D ociperlimab + tislelizumab 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 disease control rate (DCR), duration of response (DOR) and safety.
Results: As of June 20, 2022, 26 patients were enrolled; 25 were efficacy-evaluable. Median study follow-up was 46.1 weeks (range, 25.4-59.0). Confirmed ORR was 8.0% (95% CI, 1.0-26.0), with 2 patients experiencing partial response. Confirmed DCR was 56.0% (95% CI, 34.9-75.6); median DOR was not reached. Overall, 23 patients (88.5%) experienced ≥1 treatment-emergent adverse event (TEAE), 11 patients (42.3%) experienced Grade≥3 TEAEs, and 9 patients (34.6%) experienced serious TEAEs. The most common TEAEs were fatigue (30.8%) and cough (26.9%). TEAEs leading to treatment discontinuation occurred in 4 patients (15.4%), of which 2 were related to treatment; no TEAEs led to death.
Conclusions: Ociperlimab 900mg + tislelizumab 200mg was generally well-tolerated and showed preliminary antitumor activity in patients with locally advanced/metastatic CPI-experienced NSCLC.