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.

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:

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.

• Authors: Giuseppe Curigliano, Hans Gelderblom, Nicolas Mach, Toshihiko Doi, David Tai, Patrick M Forde, John Sarantopoulos, Philippe L Bedard, Chia-Chi Lin, F Stephen Hodi, Sofie Wilgenhof, Armando Santoro, Catherine A Sabatos-Peyton, Tyler A Longmire, Alexandros Xyrafas, Haiying Sun, Sabine Gutzwiller, Luigi Manenti, Aung Naing
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 27 Issue 13 Pg. 3620-3629 (07 01 2021) ISSN: 1557-3265 [Electronic] United States
• PMID: 33883177 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2021 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Drug Combinations
• HAVCR2 protein, human
• Hepatitis A Virus Cellular Receptor 2
• Immune Checkpoint Inhibitors
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• spartalizumab
• sabatolimab

Topics

• Adult
• Aged
• Aged, 80 and over
• Female
• Humans
• Male
• Middle Aged
• Young Adult
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Drug Combinations
• Hepatitis A Virus Cellular Receptor 2 (immunology)
• Immune Checkpoint Inhibitors (administration & dosage)
• Neoplasm Staging
• Neoplasms (drug therapy, pathology)
• Programmed Cell Death 1 Receptor (immunology)