{
  "abstract": "Background Patients with platinum-resistant/refractory ovarian cancer (PROC) experience suboptimal outcomes, highlighting an immediate need for novel therapies. This phase 1b study investigated the safety and efficacy of botensilimab (BOT), a fragment crystallizable (Fc)-enhanced anti–cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody with differentiated mechanisms of action from first-generation CTLA-4 inhibitors, plus balstilimab (BAL; anti–programmed cell death protein 1 antibody), in an expanded cohort of patients with treatment-refractory ovarian cancer.Methods BOT was administered intravenously at 1 mg/kg or 2 mg/kg every 6 weeks in combination with BAL intravenously at 3 mg/kg every 2 weeks (up to 2 years). The primary objectives were to assess safety and tolerability. Efficacy end points included objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1. Overall survival (OS) was an exploratory end point.Results Overall, 44 patients were evaluable for safety (with a median of 3 prior lines of therapy; median follow-up 9.6 months (range, 0.6—36.6)), and 35 for efficacy. The most common treatment-related adverse event was diarrhea/colitis (43%; 16% grade 3) with no treatment-related deaths. RECIST-confirmed ORR was 23% (8/35; 95% CI 10% to 40%; one complete (CR), seven partial responses (PRs)) and clinical benefit rate (CR, PR, or stable disease ≥24 weeks) was 31% (11/35; 95% CI 17% to 49%). Median DOR was 9.7 months (95% CI 2.8 to not reached (NR)), median PFS was 2.8 months (95% CI 1.4 to 5.5), median OS was 14.8 months (95% CI 12.1 to NR), and 12-month OS was 75% (95% CI 55% to 86%). Immune phenotypic analyses and biomarker data revealed significantly higher FcγRIIIA+CD11c+ cells and higher programmed death-ligand 1 expression in responding patients, a strong association between T-cell infiltrated tumors and clinical benefit, and differences in immune architecture across histologic subtypes.Conclusion The BOT/BAL combination demonstrated deep, durable responses and complete remissions in patients with treatment-refractory ovarian cancer where no standard treatments are currently available. RECIST under-represented clinical benefit with 11 patients achieving prolonged/clinically meaningful stable disease (or better) for ≥24 weeks. Toxicities were manageable and reversible. The encouraging clinical activity of BOT/BAL in heavily pretreated patients, as well as biomarker associations, warrants further investigation of this combination.",
  "authors": [
    {
      "affiliations": [
        "Dana-Farber Cancer Institute, Boston, Massachusetts, USA"
      ],
      "name": "Rebecca Porter"
    },
    {
      "affiliations": [
        "Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA"
      ],
      "name": "Bruno Bockorny"
    },
    {
      "affiliations": [
        "University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, Colorado, USA"
      ],
      "name": "Bradley R Corr"
    },
    {
      "affiliations": [
        "The University of Texas Health Sciences Center at San Antonio, San Antonio, Texas, USA"
      ],
      "name": "Daruka Mahadevan"
    },
    {
      "affiliations": [
        "University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, Colorado, USA"
      ],
      "name": "Breelyn A Wilky"
    },
    {
      "affiliations": [
        "University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, USA"
      ],
      "name": "Anthony B El-Khoueiry"
    },
    {
      "affiliations": [
        "Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA"
      ],
      "name": "Andrea J Bullock"
    },
    {
      "affiliations": [
        "The Angeles Clinic and Research Institute, Los Angeles, California, USA"
      ],
      "name": "Navid Hafez"
    },
    {
      "affiliations": [
        "HonorHealth Research Institute, Scottsdale, Arizona, USA"
      ],
      "name": "Justin Moser"
    },
    {
      "affiliations": [
        "University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, USA"
      ],
      "name": "Anastasia Martynova"
    },
    {
      "affiliations": [
        "Anglia Ruskin University, School of Life Sciences, Cambridge, England, UK"
      ],
      "name": "Justin Stebbing"
    },
    {
      "affiliations": [
        "Agenus Inc, Lexington, Massachusetts, USA"
      ],
      "name": "Bishnu Joshi"
    },
    {
      "affiliations": [
        "Agenus Inc, Lexington, Massachusetts, USA"
      ],
      "name": "Sean Bourdelais"
    },
    {
      "affiliations": [
        "Agenus Inc, Lexington, Massachusetts, USA"
      ],
      "name": "Chloe Delepine"
    },
    {
      "affiliations": [
        "Agenus Inc, Lexington, Massachusetts, USA"
      ],
      "name": "Dhan Chand"
    },
    {
      "affiliations": [
        "Agenus Inc, Lexington, Massachusetts, USA"
      ],
      "name": "Wei Wu"
    },
    {
      "affiliations": [
        "Agenus Inc, Lexington, Massachusetts, USA"
      ],
      "name": "Benny Johnson"
    },
    {
      "affiliations": [
        "Agenus Inc, Lexington, Massachusetts, USA"
      ],
      "name": "Joseph E Grossman"
    },
    {
      "affiliations": [
        "Agenus Inc, Lexington, Massachusetts, USA"
      ],
      "name": "Steven J O’Day"
    },
    {
      "affiliations": [
        "Dana-Farber Cancer Institute, Boston, Massachusetts, USA"
      ],
      "name": "Ursula A Matulonis"
    },
    {
      "affiliations": [
        "HonorHealth Research Institute, Scottsdale, Arizona, USA"
      ],
      "name": "Michael S Gordon"
    }
  ],
  "title": "Botensilimab (Fc-enhanced anti–CTLA-4 antibody) plus balstilimab (anti–PD-1 antibody) in patients with treatment-refractory ovarian cancer",
  "uid": "5ea42139-6f6a-5485-a5c2-826d1e73f95f"
}