{
  "abstract": "Background The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib delays disease progression in dedifferentiated liposarcoma (DDLPS) by inducing tumor cell quiescence or senescence, though most tumors ultimately progress. Preclinical data suggest CDK4/6 inhibition enhances intratumoral inflammation and may synergize with immune checkpoint inhibitors.Methods This non-randomized, open-label, phase 2 study was conducted at Memorial Sloan Kettering Cancer Center. Patients with metastatic or unresectable DDLPS, or those expected to benefit from systemic therapy prior to surgery, were eligible. Patients received palbociclib (125 mg orally, days 1–21 of a 28-day cycle) plus retifanlimab (500 mg intravenous flat dose every 4 weeks). The primary endpoint was to assess the best objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.Results 30 patients were treated and evaluable. Median age was 61 years (range 36–81), 67% were male, and 63% were treatment-naive. The median follow-up was 14.8 months. ORR was 20% (95% CI 8% to 39%) and the clinical benefit rate was 53% (95% CI 34% to 72%). Median progression-free survival and overall survival were 4.8 (95% CI 1.71 to 15.7) and 27 months (95% CI 21.7 to not reached (NR)), respectively. Median duration of response was 18.4 months (95% CI 9.4 months to NR). Grade ≥3 treatment-related adverse events occurred in 61% of patients, including one Grade 4 neutropenia. There were no Grade 5 events. Retifanlimab and palbociclib were discontinued due to toxicity in 23% and 17% of patients, respectively. Tumor sequencing identified JUN amplification in 6 of 14 patients with progressive disease versus 2 patients with stable disease or partial response. Patients with progressive disease had a higher median copy number alteration burden compared with those with stable disease or partial response.Conclusions Palbociclib plus retifanlimab demonstrated deep and durable responses in a subset of patients with advanced DDLPS, with an ORR exceeding that historically observed with either agent alone. Adverse events were generally manageable. Copy number alteration burden and JUN amplification merit further evaluation as potential biomarkers of resistance.Trial registration number https://clinicaltrials.gov/study/NCT04438824.",
  "authors": [
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Evan Rosenbaum"
    },
    {
      "affiliations": [
        "Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Kenneth Seier"
    },
    {
      "affiliations": [
        "Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Rodrigo Gularte-Mérida"
    },
    {
      "affiliations": [
        "Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Evan Seffar"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Mark A Dickson"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Viswatej Avutu"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Lauren B Banks"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Jason E Chan"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Ping Chi"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Mrinal M Gounder"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Ciara M Kelly"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Mary L Keohan"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Robert G Maki"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Sujana Movva"
    },
    {
      "affiliations": [
        "Department on Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Damon Reed"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Rhoena Desir"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Matthew Biniakewitz"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Jae-Mun Cho"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Michele Duchemin"
    },
    {
      "affiliations": [
        "Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Joseph P Erinjeri"
    },
    {
      "affiliations": [
        "Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Robert A Lefkowitz"
    },
    {
      "affiliations": [
        "Sloan-Kettering Institute, New York, New York, USA"
      ],
      "name": "Andrew Koff"
    },
    {
      "affiliations": [
        "Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Surgery, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Samuel Singer"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "William Tap"
    },
    {
      "affiliations": [
        "Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Li-Xuan Qin"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Sandra D’Angelo"
    }
  ],
  "title": "Phase 2 study of palbociclib plus retifanlimab in patients with advanced dedifferentiated liposarcoma",
  "uid": "1ef1f2fe-4f8b-54bd-a746-1c0d443f85eb"
}