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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

Sylvie Rottey (UGent) , Jeffrey Clarke, Kyaw Aung, Jean-Pascal Machiels, Ben Markman, Kimberley M. Heinhuis, Michael Millward, Martijn Lolkema, Sandip Pravin Patel, Paul de Souza, et al.
(2022) CLINICAL CANCER RESEARCH. 28(1). p.95-105
Author
Organization
Abstract
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 [NCE02341625 (CA008-002)], patients received BMS-986 148 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%) treatmentrelated 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 observ ed 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.
Keywords
Cancer Research, Oncology, TUBULYSIN, TARGET, OVEREXPRESSION, IMMUNOTHERAPY, SURVIVAL, AGENT

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MLA
Rottey, Sylvie, et al. “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.” CLINICAL CANCER RESEARCH, vol. 28, no. 1, 2022, pp. 95–105, doi:10.1158/1078-0432.ccr-21-1181.
APA
Rottey, S., Clarke, J., Aung, K., Machiels, J.-P., Markman, B., Heinhuis, K. M., … Chu, Q. S.-C. (2022). 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. CLINICAL CANCER RESEARCH, 28(1), 95–105. https://doi.org/10.1158/1078-0432.ccr-21-1181
Chicago author-date
Rottey, Sylvie, Jeffrey Clarke, Kyaw Aung, Jean-Pascal Machiels, Ben Markman, Kimberley M. Heinhuis, Michael Millward, et al. 2022. “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.” CLINICAL CANCER RESEARCH 28 (1): 95–105. https://doi.org/10.1158/1078-0432.ccr-21-1181.
Chicago author-date (all authors)
Rottey, Sylvie, Jeffrey Clarke, Kyaw Aung, Jean-Pascal Machiels, Ben Markman, Kimberley M. Heinhuis, Michael Millward, Martijn Lolkema, Sandip Pravin Patel, Paul de Souza, Matteo Duca, Giuseppe Curigliano, Armando Santoro, Takafumi Koyama, Michelle Brown, Heather Vezina, Chunsheng He, and Quincy Siu-Chung Chu. 2022. “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.” CLINICAL CANCER RESEARCH 28 (1): 95–105. doi:10.1158/1078-0432.ccr-21-1181.
Vancouver
1.
Rottey S, Clarke J, Aung K, Machiels J-P, Markman B, Heinhuis KM, et al. 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. CLINICAL CANCER RESEARCH. 2022;28(1):95–105.
IEEE
[1]
S. Rottey et al., “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,” CLINICAL CANCER RESEARCH, vol. 28, no. 1, pp. 95–105, 2022.
@article{8730488,
  abstract     = {{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 [NCE02341625 (CA008-002)], patients received BMS-986 148 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%) treatmentrelated 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 observ ed 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.}},
  author       = {{Rottey, Sylvie and Clarke, Jeffrey and Aung, Kyaw and Machiels, Jean-Pascal and Markman, Ben and Heinhuis, Kimberley M. and Millward, Michael and Lolkema, Martijn and Patel, Sandip Pravin and de Souza, Paul and Duca, Matteo and Curigliano, Giuseppe and Santoro, Armando and Koyama, Takafumi and Brown, Michelle and Vezina, Heather and He, Chunsheng and Chu, Quincy Siu-Chung}},
  issn         = {{1078-0432}},
  journal      = {{CLINICAL CANCER RESEARCH}},
  keywords     = {{Cancer Research,Oncology,TUBULYSIN,TARGET,OVEREXPRESSION,IMMUNOTHERAPY,SURVIVAL,AGENT}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{95--105}},
  title        = {{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}},
  url          = {{http://doi.org/10.1158/1078-0432.ccr-21-1181}},
  volume       = {{28}},
  year         = {{2022}},
}
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