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

  • Giuseppe Curigliano
    1Istituto Europeo di Oncologia, IRCCS, and Department of Oncology and Hemato-Oncology, University of Milano, Milano, Italy.
  • Hans Gelderblom
    2Leiden University Medical Center, Leiden, the Netherlands.
  • Nicolas Mach
    3Oncology Department, Geneva University Hospitals, Geneva, Switzerland.
  • Toshihiko Doi
    4National Cancer Center Hospital East, Kashiwa, Japan.
  • David Tai
    5National Cancer Centre Singapore, Singapore, Singapore.
  • Patrick M. Forde
    6Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • John Sarantopoulos
    7Institute for Drug Development, Mays Cancer Center at University of Texas Health San Antonio MD Anderson Cancer Center, San Antonio, Texas.
  • Philippe L. Bedard
    8Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
  • Chia-Chi Lin
    9National Taiwan University Hospital, Taipei, Taiwan.
  • F. Stephen Hodi
    10Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Sofie Wilgenhof
    11Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
  • Armando Santoro
    12Humanitas University, Pieve Emanuele, and Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy.
  • Catherine A. Sabatos-Peyton
    13Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
  • Tyler A. Longmire
    13Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
  • Alexandros Xyrafas
    14Novartis Pharma AG, Basel, Switzerland.
  • Haiying Sun
    13Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
  • Sabine Gutzwiller
    14Novartis Pharma AG, Basel, Switzerland.
  • Luigi Manenti
    15Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
  • Aung Naing
    16MD Anderson Cancer Center, Houston, Texas.

抄録

<jats:title>Abstract</jats:title><jats:sec><jats:title>Purpose:</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Patients and Methods:</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>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 &gt;10% TIM-3–positive staining, including one patient with NSCLC who received prior PD-1 therapy.</jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p>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.</jats:p></jats:sec>

収録刊行物

  • Clinical Cancer Research

    Clinical Cancer Research 27 (13), 3620-3629, 2021-04-21

    American Association for Cancer Research (AACR)

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