PURPOSE: Sabatolimab (MBG453) and spartalizumab are monoclonal antibodies that bind T-cell immunoglobulin domain and mucin domain-3 (TIM-3) and programed death-1 (PD-1), respectively. This phase I/II study evaluated the safety and efficacy of sabatolimab, with or without spartalizumab, in patients with advanced solid tumors. EXPERIMENTAL DESIGN: Primary objectives of the phase I/Ib part were to characterize the safety and estimate recommended doses for future studies (RP2Ds). Dose escalation was guided by a Bayesian (hierarchical) logistic regression model. Sabatolimab was administered intravenously, 20-1200 mg, every 2 or 4 weeks (Q2W, Q4W). Spartalizumab was administered intravenously, 80-400 mg, Q2W or Q4W. RESULTS: Enrolled patients (n=219) had a range of cancers, most commonly ovarian (17%) and colorectal cancer (7%); patients received sabatolimab (n=133) or sabatolimab plus spartalizumab (n=86). The maximum tolerated dose was not reached. The most common adverse event suspected to be treatment-related was fatigue (9%, sabatolimab; 15%, combination). No responses were seen with sabatolimab. Five patients receiving combination treatment had partial responses (6%; lasting 12-27 months), in colorectal cancer (n=2), non-small cell lung cancer (NSCLC), malignant perianal melanoma, and SCLC. Of the five, two patients had elevated expression of immune markers in baseline biopsies; another three had >10% TIM-3 positive staining, including one patient with NSCLC who received prior PD-1 therapy. CONCLUSIONS: Sabatolimab plus spartalizumab was well tolerated and showed preliminary signs of antitumor activity. The RP2D for sabatolimab was selected as 800 mg Q4W (alternatively Q3W or Q2W schedules, based on modeling), with or without 400 mg spartalizumab Q4W.

Author Info: (1) Department of Oncology and Hemato-Oncology, University of Milano, Milano, Italy, European Institute of Oncology, IRCCS, Milano, Italy giuseppe.curigliano@ieo.it. (2) Department

Author Info: (1) Department of Oncology and Hemato-Oncology, University of Milano, Milano, Italy, European Institute of Oncology, IRCCS, Milano, Italy giuseppe.curigliano@ieo.it. (2) Department of Clinical Oncology, Leiden University Medical Center. (3) Clinical Research Unit of the Foundation Dr. Henri Dubois-Ferrière Dinu Lipatti, Hôpitaux Universitaires de Genève (HUG). (4) Department of Experimental Therapeutics, National Cancer Center Hospital East. (5) Department of Medical Oncology, Humphrey Oei Institute of Cancer Research, National Cancer Centre. (6) The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine. (7) medicine, Institute for Drug Development, Mays Cancer Center at University of Texas Health San Antonio MD Anderson Cancer Center. (8) Dvision of Medical Oncology & Hematology, Princess Margaret Cancer Centre. (9) Department of Oncology, National Taiwan University Hospital. (10) Medical Oncology, Dana-Farber Cancer Institute. (11) Department of Medical Oncolocy, Netherlands Cancer Institute - Antoni van Leeuwenhoek. (12) Department of Oncology and Hematology, IRCCS Humanitas Research Hospital. (13) Novartis Institutes for BioMedical Research. (14) Exploratory Immuno-oncology, Novartis Institute of Biomedical Research. (15) GDD, Novartis Pharma AG. (16) Novartis Institutes for BioMedical Research. (17) Novartis Pharma AG. (18) Novartis Pharmaceuticals Corporation. (19) Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center.