{
  "abstract": "Background Cysteine–cysteine chemokine receptors 2 (CCR2) and 5 (CCR5) contribute to immune suppression in tumor microenvironments. CCR2 and CCR5 antagonists have demonstrated antitumor activity in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), respectively. This phase 1b/2, open-label study evaluated BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy±nivolumab in advanced PDAC or metastatic CRC.Methods Part 1 included patients with metastatic untreated (first-line (1L)) PDAC, 1L CRC, or previously treated (second or third line (2/3L)) microsatellite stable (MSS) CRC. Patients received 2 weeks of BMS-813160 monotherapy (300 mg two times a day, 600 mg once daily, 300 mg once daily, or 150 mg once daily) and then BMS-813160+chemotherapy (gemcitabine+nab-paclitaxel (gem/nabP; 1L PDAC), 5-fluorouracil+leucovorin+irinotecan (FOLFIRI; 1L CRC)), or nivolumab (2/3L MSS CRC).Part 2 included patients with metastatic 1L PDAC or 2L CRC. Patients received BMS-813160 300 mg two times a day+gem/nabP±nivolumab (1L PDAC), BMS-813160 300 mg two times a day or 150 mg once daily+FOLFIRI (2L CRC), or chemotherapy alone. Primary endpoints were safety and pharmacodynamics (Part 1) and efficacy (Part 2).Results In Part 1, 22 of 75 (29%) and 54 of 72 (72%) patients experienced a treatment-related adverse event during monotherapy lead-in and overall, respectively. Two dose-limiting toxicities (rash and pericardial effusion with pericarditis, both grade 3) occurred. In Part 2, patients with 1L PDAC who received BMS-813160 300 mg two times a day+gem/nabP+nivolumab achieved an overall response rate (ORR) of 37% (13/35); the median duration of response (DOR) was 45 weeks (95% CI 26.1 to not evaluable). ORRs with BMS-813160 300 mg two times a day+gem/nabP and gem/nabP alone were 26% (9/35) and 28% (9/32), respectively; median DORs were 121 and 31 weeks, respectively. Progression-free survival rates at 24 weeks were 56% (BMS-813160 300 mg two times a day+gem/nabP+nivolumab), 56% (BMS-813160 300 mg two times a day+gem/nabP), and 50% (gem/nabP). ORRs in 2L CRC were 19% (6/32; BMS-813160 300 mg two times a day+FOLFIRI), 13% (4/32; BMS-813160 150 mg once daily+FOLFIRI), and 27% (7/26; FOLFIRI).Conclusions In 1L PDAC, BMS-813160 300 two times a day+gem/nabP±nivolumab demonstrated durable antitumor response and was well tolerated. BMS-813160 combination regimens were tolerable in other cohorts, but clinical efficacy was not demonstrated.Trial registration number NCT03184870.",
  "authors": [
    {
      "affiliations": [
        "Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA"
      ],
      "name": "Dung T Le"
    },
    {
      "affiliations": [
        "Medical Department I, TU Dresden/Universitaetsklinikum Carl Gustav Carus, Dresden, Germany"
      ],
      "name": "Gunnar Folprecht"
    },
    {
      "affiliations": [
        "Memorial Sloan Kettering Nassau, Uniondale, New York, USA"
      ],
      "name": "Anna M Varghese"
    },
    {
      "affiliations": [
        "Hackensack University Medical Center Center, Hackensack, New Jersey, USA"
      ],
      "name": "Martin Gutierrez"
    },
    {
      "affiliations": [
        "Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, DC, USA"
      ],
      "name": "Marcus Noel"
    },
    {
      "affiliations": [
        "Washington University School of Medicine in Saint Louis, St Louis, Missouri, USA"
      ],
      "name": "Nikolaos A Trikalinos"
    },
    {
      "affiliations": [
        "Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada"
      ],
      "name": "Eric Chen"
    },
    {
      "affiliations": [
        "UC Irvine Medical Center, Orange, Florida, USA"
      ],
      "name": "Farshid Dayyani"
    },
    {
      "affiliations": [
        "University of Colorado Cancer Center, Denver, Colorado, USA"
      ],
      "name": "S Lindsey Davis"
    },
    {
      "affiliations": [
        "Mayo Clinic in Minnesota, Rochester, Minnesota, USA"
      ],
      "name": "Wen Wee Ma"
    },
    {
      "affiliations": [
        "Thomas Jefferson University, Philadelphia, Pennsylvania, USA"
      ],
      "name": "Atrayee BasuMallick"
    },
    {
      "affiliations": [
        "Huntsman Cancer Institute, Salt Lake City, Utah, USA"
      ],
      "name": "Ignacio Garrido-Laguna"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb Co, Princeton, New Jersey, USA"
      ],
      "name": "Mayu Osawa"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb Co, Princeton, New Jersey, USA"
      ],
      "name": "Shaun O’Brien"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb Co, Princeton, New Jersey, USA"
      ],
      "name": "Ruslan D Novosiadly"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb Co, Princeton, New Jersey, USA"
      ],
      "name": "Ke Xu"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Lawrenceville, New Jersey, USA"
      ],
      "name": "Danielle M Greenawalt"
    },
    {
      "affiliations": [
        "Biostatistics, Bristol Myers Squibb, Princeton, New Jersey, USA"
      ],
      "name": "Santanu Dutta"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb Co, Princeton, New Jersey, USA"
      ],
      "name": "Christina Twyman Saint Victor"
    },
    {
      "affiliations": [
        "USC Norris Comprehensive Cancer Center, Los Angeles, California, USA"
      ],
      "name": "Heinz-Josef Lenz"
    }
  ],
  "title": "Phase 1b/2 study of BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy or nivolumab in patients with advanced pancreatic or colorectal cancer",
  "uid": "01283e26-d6a4-5fdd-8ce5-7736d7edb621"
}