{
  "abstract": "Background Dual anti-CTLA-4/PD-1 inhibitors show efficacy in numerous malignancies. We are the first to report on the efficacy of ipilimumab-nivolumab immunotherapy in a dedicated cohort of patients with gynecologic clear cell carcinomas (CCCs), which are rare, aggressive cancers.Methods DART is a multicenter, multicohort phase II trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks), with primary objective as Response Evaluation Criteria in Solid Tumors (RECIST)-based overall response rate (ORR). Secondary objectives were ORR by immune RECIST (iRECIST), progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR; overall response plus stable disease (SD) ≥6 months), and toxicity.Results Overall, in this cohort of 32 patients with gynecologic CCC (N=19 ovarian, N=8 endometrial, N=5 cervical; 1–8 prior therapies; 3 had prior PD-1 inhibitor exposure), an ORR of 9.38% was seen. This included two complete responses (CRs) (both ovarian origin) that are ongoing at >3 years and one partial response (PR). Overall ORR increased to 12.5% when including one PR by iRECIST criteria for a patient with cervical CCC lasting 26 months, with an OS of 32.0 months. The CBR was 21.88% overall for all 32 (7/32) evaluable patients with gynecologic CCC. This included two CR, one PR, and two patients with SD >6 months with ovarian CCC and one PR by iRECIST and one SD >6 months in two patients with cervical CCC. PFS for the seven patients with CBR was 63.6+, 47.8+, 40.5+, 50.8+, 7.4, 26, and 58.1+ months. Median OS was 21.7 months for all 32 evaluable patients. Seven of 32 patients (21.9%) discontinued therapy because of toxicity; there were no treatment-related deaths.Conclusions Ipilimumab plus nivolumab demonstrated durable antitumor activity in certain patients with CCC of gynecological origin, particularly in those with CCC of ovarian origin. Safety is consistent with the known profile of ipilimumab and nivolumab. Correlative studies to better identify which patients will respond to combined ipilimumab and nivolumab are ongoing.Trial registration number NCT02834013.",
  "authors": [
    {
      "affiliations": [
        "Northwestern University, Chicago, Illinois, USA"
      ],
      "name": "Young Kwang Chae"
    },
    {
      "affiliations": [
        "SWOG Statistics and Data Management Center, Seattle, Washington, USA"
      ],
      "name": "Megan Othus"
    },
    {
      "affiliations": [
        "University of California at San Diego Moores Cancer Center, Sacramento, La Jolla, USA"
      ],
      "name": "Sandip P Patel"
    },
    {
      "affiliations": [
        "Ohio State University, Columbus, Ohio, USA"
      ],
      "name": "Floortje J Backes"
    },
    {
      "affiliations": [
        "Ohio State University, Columbus, Ohio, USA"
      ],
      "name": "David M O’Malley"
    },
    {
      "affiliations": [
        "City of Hope Comprehensive Cancer Center, Duarte, California, USA"
      ],
      "name": "Mihaela Cristea"
    },
    {
      "affiliations": [
        "MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Aung Naing"
    },
    {
      "affiliations": [
        "University of Chicago, Chicago, Illinois, USA"
      ],
      "name": "Katherine Kurnit"
    },
    {
      "affiliations": [
        "University of California at San Diego Moores Cancer Center, Sacramento, La Jolla, USA"
      ],
      "name": "Ramez N Eskander"
    },
    {
      "affiliations": [
        "Parkview Regional Medical Center, Fort Wayne, Indiana, USA"
      ],
      "name": "Scott T Goodrich"
    },
    {
      "affiliations": [
        "Tulane University School of Medicine, New Orleans, Louisiana, USA"
      ],
      "name": "William R Robinson"
    },
    {
      "affiliations": [
        "University of South Alabama Mitchell Cancer Institute, South Alabama, Alabama, USA"
      ],
      "name": "Jennifer Scalici"
    },
    {
      "affiliations": [
        "California Pacific Medical Center Pacific Campus, San Francisco, California, USA"
      ],
      "name": "John Chan"
    },
    {
      "affiliations": [
        "Michigan CRC NCORP, Ann Arbor, Michigan, USA"
      ],
      "name": "Hussein Ali-Ahmad"
    },
    {
      "affiliations": [
        "Ohio State University, Columbus, Ohio, USA"
      ],
      "name": "John Hays"
    },
    {
      "affiliations": [
        "Legacy Good Samaritan Hospital and Medical Center, Portland, Oregon, USA"
      ],
      "name": "Colleen McCormick"
    },
    {
      "affiliations": [
        "University of California Davis, Davis, California, USA"
      ],
      "name": "Edward J Kim"
    },
    {
      "affiliations": [
        "Kaiser Permanente NCORP, Honolulu, Hawaii, USA"
      ],
      "name": "Thanasak Sueblinvong"
    },
    {
      "affiliations": [
        "Rush University Medical Center, Chicago, Illinois, USA"
      ],
      "name": "Amina Ahmed"
    },
    {
      "affiliations": [
        "University of Michigan, Ann Arbor, Michigan, USA"
      ],
      "name": "Jean Siedel"
    },
    {
      "affiliations": [
        "Minnesota Oncology Hematology PA, Woodbury, Minnesota, USA"
      ],
      "name": "Jessica Thomes Pepin"
    },
    {
      "affiliations": [
        "Montana NCORP, Bozeman, Montana, USA"
      ],
      "name": "Justin Neal Bottsford-Miller"
    },
    {
      "affiliations": [
        "Wisconsin NCORP, Marshfield, Wisconsin, USA"
      ],
      "name": "Seth Olusegun Fagbemi"
    },
    {
      "affiliations": [
        "Wisconsin NCORP, Marshfield, Wisconsin, USA"
      ],
      "name": "Anthony John Jaslowski"
    },
    {
      "affiliations": [
        "Northwestern University, Chicago, Illinois, USA",
        "Temple University Hospital, Philadelphia, Pennsylvania, USA"
      ],
      "name": "Hye Sung Kim"
    },
    {
      "affiliations": [
        "Northwestern University, Chicago, Illinois, USA"
      ],
      "name": "Liam Il-Young Chung"
    },
    {
      "affiliations": [
        "Northwestern University, Chicago, Illinois, USA"
      ],
      "name": "Carolyn Moloney-Lineen"
    },
    {
      "affiliations": [
        "SWOG Data Operations Center, Seattle, Washington, USA"
      ],
      "name": "Christine M McLeod"
    },
    {
      "affiliations": [
        "National Cancer Institute, Investigational Drug Branch, Cancer Therapy Evaluation Program, Bethesda, Maryland, UK"
      ],
      "name": "Helen X Chen"
    },
    {
      "affiliations": [
        "National Cancer Institute, Investigational Drug Branch, Cancer Therapy Evaluation Program, Bethesda, Maryland, UK"
      ],
      "name": "Elad Sharon"
    },
    {
      "affiliations": [
        "National Cancer Institute, Investigational Drug Branch, Cancer Therapy Evaluation Program, Bethesda, Maryland, UK"
      ],
      "name": "Howard Streicher"
    },
    {
      "affiliations": [
        "Oregon Health and Science University, Portland, Oregon, USA"
      ],
      "name": "Christopher W Ryan"
    },
    {
      "affiliations": [
        "SWOG Group Chair’s Office, Knight Cancer Institute, Portland, Oregon, USA"
      ],
      "name": "Charles D Blanke"
    },
    {
      "affiliations": [
        "Medical College of Wisconsin, Milwaukee, Wisconsin, USA"
      ],
      "name": "Razelle Kurzrock"
    }
  ],
  "title": "DART/SWOG/NCI phase II anti-CTLA-4/PD-1 trial: clear cell carcinomas of ovary, endometrium, cervix",
  "uid": "ac06b9e2-2ee6-5767-b118-717b41bd7793"
}