TY - JOUR
T1 - Phase I/Ib clinical trial of sabatolimab, an anti–TIM-3 antibody, alone and in combination with spartalizumab, an anti–PD-1 antibody, in advanced solid tumors
AU - Curigliano, Giuseppe
AU - Gelderblom, Hans
AU - Mach, Nicolas
AU - Doi, Toshihiko
AU - Tai, David
AU - Forde, Patrick M.
AU - Sarantopoulos, John
AU - Bedard, Philippe L.
AU - Lin, Chia Chi
AU - Stephen Hodi, F.
AU - Wilgenhof, Sofie
AU - Santoro, Armando
AU - Sabatos-Peyton, Catherine A.
AU - Longmire, Tyler A.
AU - Xyrafas, Alexandros
AU - Sun, Haiying
AU - Gutzwiller, Sabine
AU - Manenti, Luigi
AU - Naing, Aung
N1 - Funding Information:
This study was sponsored by Novartis Pharmaceuticals Corporation. Funding support was received for the Institute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio, San Antonio, TX (Cancer Center Support Grant P30CA054174).
Publisher Copyright:
© 2021 American Association for Cancer Research.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - Purpose: Sabatolimab (MBG453) and spartalizumab are mAbs that bind T-cell immunoglobulin domain and mucin domain-3 (TIM-3) and programmed 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. Patients and Methods: Primary objectives of the phase I/Ib part were to characterize the safety and estimate recommended phase II dose (RP2D) for future studies. Dose escalation was guided by a Bayesian (hierarchical) logistic regression model. Sabatolimab was administered intravenously, 20 to 1,200 mg, every 2 or 4 weeks (Q2W or Q4W). Spartalizumab was administered intravenously, 80 to 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 MTD 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.
AB - Purpose: Sabatolimab (MBG453) and spartalizumab are mAbs that bind T-cell immunoglobulin domain and mucin domain-3 (TIM-3) and programmed 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. Patients and Methods: Primary objectives of the phase I/Ib part were to characterize the safety and estimate recommended phase II dose (RP2D) for future studies. Dose escalation was guided by a Bayesian (hierarchical) logistic regression model. Sabatolimab was administered intravenously, 20 to 1,200 mg, every 2 or 4 weeks (Q2W or Q4W). Spartalizumab was administered intravenously, 80 to 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 MTD 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.
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U2 - 10.1158/1078-0432.CCR-20-4746
DO - 10.1158/1078-0432.CCR-20-4746
M3 - Article
C2 - 33883177
AN - SCOPUS:85109174113
SN - 1078-0432
VL - 27
SP - 3620
EP - 3629
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 13
ER -