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
Journal
Clinical Cancer Research
Journal Volume
27
Journal Issue
13
Pages
3620-3629
Date Issued
2021
Author(s)
Curigliano G.
Gelderblom H.
Mach N.
Doi T.
Tai D.
Forde P.M.
Sarantopoulos J.
Bedard P.L.
Stephen Hodi F.
Wilgenhof S.
Santoro A.
Sabatos-Peyton C.A.
Longmire T.A.
Xyrafas A.
Sun H.
Gutzwiller S.
Manenti L.
Naing A.
Abstract
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: = 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.
SDGs
Publisher
American Association for Cancer Research Inc.
Type
journal article