Tebotelimab plus niraparib in previously treated locally advanced or metastatic solid tumors: A phase 1b dose escalation and expansion study

BACKGROUND: This open-label, single-arm, phase 1b dose escalation and expansion study (ClinicalTrials.gov identifier NCT04178460) explored the safety, tolerability, and antitumor activity of tebotelimab, a programmed cell death protein 1 × lymphocyte-activation gene 3 bispecific monoclonal antibody, in combination with niraparib, a poly(adenosine diphosphate ribose) polymerase inhibitor, in patients with gastric cancer, triple-negative breast cancer (TNBC), biliary tract carcinoma (BTC), and endometrial carcinoma. METHODS: In the escalation phase, patients with locally advanced or metastatic gastric cancer who failed ≥2 prior systemic treatments received tebotelimab (120, 300, or 600 mg) intravenously once every 2 weeks (Q2W). In the expansion phase, patients with previously treated gastric cancer, TNBC, BTC, or endometrial carcinoma received tebotelimab at the recommended phase 2 dose (RP2D). All patients received niraparib orally once daily with an individualized starting dose. RESULTS: From June 11, 2020, to January 29, 2022, 60 patients were enrolled. All received ≥1 dose of the study drug. The RP2D for tebotelimab was determined to be 600 mg Q2W, without dose-limiting toxicities observed. Grade ≥3 and serious treatment-emergent adverse events (TEAEs) occurred in 39 patients (65.0%) and 25 patients (41.7%), respectively, with no treatment-related death. Immune-related TEAEs occurred in 28 patients (46.7%). In those who had target lesions at baseline and received the RP2D, the investigator-assessed, confirmed overall response rate per Response Evaluation Criteria in Solid Tumors, version 1.1, was 5.3% (one of 19), 20.0% (two of 10), 8.3% (one of 12), and 0% (zero of three) for gastric cancer, TNBC, BTC, and endometrial carcinoma, respectively. CONCLUSIONS: Tebotelimab plus niraparib preliminarily demonstrated a tolerated and manageable safety profile and limited antitumor activity in patients with previously treated solid tumors.