{
  "abstract": "Background Neoadjuvant anti-PD-1 is associated with high efficacy in cutaneous squamous cell carcinoma. 1 However, little is known about the activity of neoadjuvant immunotherapy for basal cell carcinoma (BCC). Anti-PD-1 is approved second line for advanced BCC where it appears to have lower response rates compared to the first line setting.2 Responses to anti-PD-1 also seem greater for non-metastatic BCC.2 Notably, LAG-3 expression has been shown to be high within the BCC tumor microenvironment where it may function as a subdominant checkpoint to synergize with anti-PD-1.3 The current randomized prospective multicenter phase 2 trial evaluates the safety and efficacy of neoadjuvant nivolumab (NIVO, anti-PD-1) + relatlimab (RELA, anti-LAG-3) versus NIVO alone in resectable high-risk BCC.Methods This multicenter study open at multiple University of California Cancer Centers will enroll up to 30 patients with resectable high-risk BCC. High-risk BCC is defined by size 2.0 cm or greater in the head and neck region or 4.0 cm or greater for the trunk and extremities. All patients must have surgically resectable disease that is at increased risk for cosmetic disfigurement, functional defects, poor oncologic control, or anticipated to require skin grafting or free flap reconstruction, be checkpoint inhibitor naïve, with ECOG performance status of <2. Key exclusion criteria include recent radiation therapy and any prior history of myocarditis. Patients will be randomized in 2:1 fashion to receive NIVO 480 mg + RELA 160 mg or NIVO 480 mg IV every 4 weeks for up to 4 doses. Patients may forgo surgery and continue beyond 4 doses in cases of ongoing clinical benefit. Tumor tissue and peripheral blood will be interrogated for immune cell subsets and checkpoint expression before and after neoadjuvant treatment. The trial’s primary endpoint is the combined rate of pathological complete response, major pathologic response, and clinical complete response following neoadjuvant therapy with secondary endpoints including surgical de-escalation and safety.This trial uses a Simon’s minimax two-stage design for the NIVO+RELA cohort. Eleven patients will be enrolled in the first stage. If ≥2 patients respond to NIVO+RELA, the study will continue enrollment for a total of 20 patients. This design yields a type I error rate of 0.1 and power of 0.8.Trial Registration Trial Registration NCT06624475References Gross ND, Miller DM, Khushalani NI, Divi V, Ruiz ES, Lipson EJ, Meier F, Su YB, Swiecicki PL, Atlas J, Geiger JL, Hauschild A, Choe JH, Hughes BGM, Schadendorf D, Patel VA, Homsi J, Taube JM, Lim AM, Ferrarotto R, Kaufman HL, Seebach F, Lowy I, Yoo S, Mathias M, Fenech K, Han H, Fury MG, Rischin D. Neoadjuvant cemiplimab for stage II to IV cutaneous squamous-cell carcinoma. N Engl J Med. 2022 Oct 27;387(17):1557-1568.Schenk KM, Deutsch JS, Schollenberger MD, Sharfman WH, Brothers PN, Pons A, Scott JF, Bibee K, Taube JM, Topalian SL, Lipson EJ. 820P Nivolumab (NIVO) +/- relatlimab (RELA) or ipilimumab (IPI) for patients (pts) with advanced treatment-naïve or -refractory basal cell carcinoma (BCC). Annals of Oncology 33:S922-S923.Deutsch JS, Lai J, Schenk KM, Soni A, Will EM, Engle LL, Xu H, Ogurtsova A, Madan V, Chong JK, Wang D, Green BF, Nguyen P, Schollenberger MD, Lipson EJ, Taube JM. Immune microenvironment of basal cell carcinoma and tumor regression following combined PD-1/LAG-3 blockade. J Immunother Cancer. 2023 Dec 14;11(12):e007463.Ethics Approval This trial is being conducted in accordance with the Declaration of Helsinki. This study was approved by UC San Diego’s Institutional Review Board; approval number is 810617. All participants will provide written informed consent.",
  "authors": [
    {
      "affiliations": [
        "UC San Diego, La Jolla, CA, USA"
      ],
      "name": "Soo Park"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Lawrenceville, NJ, USA"
      ],
      "name": "Omid Najmi"
    },
    {
      "affiliations": [
        "UCSD Moores Cancer Center, La Jolla, CA, USA"
      ],
      "name": "Elena Alferova"
    },
    {
      "affiliations": [
        "University of California, San Francisco, San Francisco, CA, USA"
      ],
      "name": "Michael Wong"
    },
    {
      "affiliations": [
        "UCI Health Chao Family Comprehensive Cancer Center, Irvine, CA, USA"
      ],
      "name": "Poorva Vaidya"
    },
    {
      "affiliations": [
        "UCI Health Chao Family Comprehensive Cancer Center, Irvine, CA, USA"
      ],
      "name": "Warren A Chow"
    },
    {
      "affiliations": [
        "University of California, San Francisco, San Francisco, CA, USA"
      ],
      "name": "Adil Daud"
    },
    {
      "affiliations": [
        "UC San Diego Health, San Diego, CA, USA"
      ],
      "name": "Gregory A Daniels"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Lawrenceville, NJ, USA"
      ],
      "name": "Silvia Boffo"
    }
  ],
  "title": "604 Phase 2 study of neoadjuvant nivolumab + relatlimab versus nivolumab in patients with resectable high-risk basal cell carcinoma",
  "uid": "a26f56d3-ec03-587b-afec-0fc350b3c575"
}