Phase I/IIa Trial of BMS-986148, an Anti-mesothelin Antibody-drug Conjugate, Alone or in Combination with Nivolumab in Patients with Advanced Solid Tumors.

Journal Article (Journal Article)

PURPOSE: To assess the safety and tolerability of BMS-986148, a mesothelin-directed antibody-drug conjugate (ADC) ± nivolumab, in patients with selected tumors. PATIENTS AND METHODS: In an international phase I/IIa study [NCT02341625 (CA008-002)], patients received BMS-986148 monotherapy (0.1-1.6 mg/kg intravenously (i.v.) every 3 weeks or 0.4 or 0.6 mg/kg i.v. once weekly; n = 96) or BMS-986148 0.8 mg/kg + nivolumab 360 mg i.v. every 3 weeks (n = 30). The primary endpoint was safety and tolerability. RESULTS: In CA008-002, the most common (≥ 10%) treatment-related adverse events (TRAEs) included increased aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Grade 3/4 TRAEs occurred in 42 patients (49%) receiving BMS-986148 every 3 weeks monotherapy, three (25%) receiving BMS-986148 once-weekly monotherapy, and 10 (33%) receiving BMS-986148 + nivolumab every 3 weeks. Overall, 17 of 126 patients (13%) discontinued because of a TRAE. The MTD of BMS-986148 was 1.2 mg/kg i.v. every 3 weeks. The safety profile of BMS-986148 + nivolumab was similar to that of BMS-986148 monotherapy (0.8 mg/kg). Active ADC exposures increased in a dose-proportional manner with both dosing regimens (every 3 weeks and once weekly). Preliminary clinical activity was observed with BMS-986148 ± nivolumab. No association between mesothelin expression and response was detected. CONCLUSIONS: BMS-986148 ± nivolumab demonstrated a clinically manageable safety profile and preliminary evidence of clinical activity, supporting additional studies combining directed cytotoxic therapies with checkpoint inhibitors as potential multimodal therapeutic strategies in patients with advanced solid tumors.

Full Text

Duke Authors

Cited Authors

  • Rottey, S; Clarke, J; Aung, K; Machiels, J-P; Markman, B; Heinhuis, KM; Millward, M; Lolkema, M; Patel, SP; de Souza, P; Duca, M; Curigliano, G; Santoro, A; Koyama, T; Brown, M; Vezina, H; He, C; Chu, QS-C

Published Date

  • January 1, 2022

Published In

Volume / Issue

  • 28 / 1

Start / End Page

  • 95 - 105

PubMed ID

  • 34615718

Pubmed Central ID

  • PMC9401510

Electronic International Standard Serial Number (EISSN)

  • 1557-3265

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-21-1181


  • eng

Conference Location

  • United States