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Nivolumab with or without Ipilimumab or Relatlimab in Treating Patients with Unresectable, Metastatic, or Refractory Basal Cell Carcinoma

Trial Status: Active

This phase II trial studies how well nivolumab with or without ipilimumab or relatlimab works in treating patients with basal cell carcinoma that cannot be removed by surgery (unresectable), has spread to other places in the body (metastatic), or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, and relatlimab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Inclusion Criteria

  • Subjects must have signed and dated an Institutional Review Board (IRB)-approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care
  • Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study
  • Eastern Cooperative Group (ECOG) performance status 0-1
  • Participants with histologically confirmed basal cell carcinoma (BCC) with disease that is considered by the investigator to be unresectable or metastatic * ARM A (nivolumab monotherapy): Patients may have received up to two prior systemic therapies including hedgehog pathway inhibitors * ARM B: Patients must have refractory BCC (defined as PD or ongoing SD at 36 weeks per Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1) after receiving anti-PD-(L)1 monotherapy on CA209-8DP (Cohort A) or outside the study and relatlimab + nivolumab (Cohort C) * ARM C: Patients must have refractory BCC (defined as PD or ongoing SD at 36 weeks per RECIST v1.1) after receiving anti-PD-(L)1 monotherapy on CA209-8DP (Cohort A) or outside the study
  • Patients may not have received prior T cell modulating agents for BCC (e.g., anti-CTLA-4, antiPD-L1, anti-lymphocyte activation gene (LAG)-3, anti-KIR, etc.), except per ARM B and ARM C specifications, above
  • At least one measurable lesion by RECIST 1.1 criteria
  • Participants with Gorlin syndrome will be permitted to enroll in the study
  • White blood counts (WBC)s >= 2000/uL (obtained within day -28 to day -1 of first dose)
  • Neutrophils >= 1500/uL (obtained within day -28 to day -1 of first dose)
  • Platelets >= 100 x 10^3/uL (obtained within day -28 to day -1 of first dose)
  • Hemoglobin >= 9.0 g/dL (obtained within day -28 to day -1 of first dose)
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) >= 40 mL/minute (using Cockcroft/Gault formula) (obtained within day -28 to day -1 of first dose)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN, except in patients with liver metastases whose values may be =< 5 x ULN (obtained within day -28 to day -1 of first dose)
  • Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome who may have total bilirubin =< 3.0 mg/dL) (obtained within day -28 to day -1 of first dose)
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the initial administration of study drug, then every 4 weeks +/- 1 week thereafter for the duration of treatment with study drug(s)
  • Women must not be breastfeeding
  • WOCBP must agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with study drug(s) plus approximately 5 half-lives of study drug(s) plus 30 days (duration of ovulatory cycle) for a total of 5 months post treatment completion
  • Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus approximately 5 half-lives of study drug(s) plus 90 days (duration of sperm turnover) for a total of 7 months post-treatment completion
  • Azoospermic males and those who are continuously not heterosexually active are exempt from contraceptive requirements
  • WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements, however they must still undergo pregnancy testing as described
  • Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly. At a minimum, subjects must agree to the use one highly effective method of contraception

Exclusion Criteria

  • Pregnant or nursing women
  • Central nervous system metastases, unless stable for at least 4 weeks and no longer requiring steroid therapy
  • Patients with an autoimmune disease or with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications may be permitted to enroll only after discussion with the study principal investigator (P.I.)
  • Participants with a known history of human immunodeficiency virus (HIV) or a known history of acquired immunodeficiency syndrome (AIDS)
  • Participants with a known history of viral hepatitis: * Participants with active hepatitis B (positive hepatitis B surface antigen [HBsAg]) or hepatitis C virus (HCV) (positive HCV ribonucleic acid [RNA]) are excluded * Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and the absence of HBsAg) are not ineligible, but HBV deoxyribonucleic acid (DNA) quantification must be performed and results discussed with the P.I. * HBV carriers or those participants requiring antiviral therapy are not eligible to participate * Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA after discussion with the study P.I.
  • Participants with a prior malignancy active within the previous 2 years may be permitted to enroll only after discussion with the study P.I. Examples might include locally curable cancers that have been apparently cured, such as squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
  • Organ transplant recipients with a functioning allograft will be excluded from this study
  • For Cohorts B and C, patients will be excluded from the study if they previously experienced a toxicity to immunotherapy that, in the opinion of the investigator, would make it unsafe to restart therapy. Examples may include a grade 3 or greater immune-mediated adverse event that was considered related to previous immunotherapy and required immunosuppressive therapy, or an immune-mediated adverse event that was considered related to previous immunotherapy and is still > grade 1 despite administration of immunosuppressive therapy. Exceptions may include grade 3 ophthalmologic immune-mediated events that improved to grade 1 within 2 weeks after topical therapy only, or grade 3 endocrine immune-mediated events that did not result in symptoms lasting > 6 weeks and are not requiring > 7.5 mg prednisone or equivalent per day
  • History of severe allergy or hypersensitivity to study drug components
  • Prisoners or subjects who are involuntarily incarcerated
  • Participants who are detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE
Contact: Evan Jacob Lipson
Phone: 410-955-8893

PRIMARY OBJECTIVE:

I. To assess objective response rate (ORR).

SECONDARY OBJECTIVES:

I. To assess progression-free survival (PFS), duration of response (DOR) and overall survival (OS).

II. To assess disease control rate (DCR; complete response [CR] + partial response [PR] + stable disease [SD] >= 26 weeks).

EXPLORATORY OBJECTIVE:

I. To assess potential predictive biomarkers of treatment efficacy.

OUTLINE: Patients are assigned to 1 of 3 cohorts.

COHORT A: Patients receive nivolumab intravenously (IV) over 30-90 minutes on day 1. Cycles repeat every 4 weeks for up to 48 weeks in the absence of disease progression or unacceptable toxicity. Patients who exhibit progressive disease at 36 weeks may move to Cohort C per physician discretion.

COHORT B: Patients receive nivolumab IV over 30-90 minutes and ipilimumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning 6 weeks after final dose of combination, patients receive nivolumab IV over 30-90 minutes on day 1. Treatment repeats every 4 weeks for 7 cycles in the absence of disease progression or unacceptable toxicity.

COHORT C: Patients receive nivolumab IV over 30-90 minutes and relatlimab IV over 30 minutes on day 1. Cycles repeat every 4 weeks for up to 48 weeks in the absence of disease progression or unacceptable toxicity. Patients who exhibit progressive disease at 36 weeks may move to Cohort B per physician discretion.

After completion of study treatment, patients are followed up every 8 weeks for year 1, every 12 weeks for year 2, every 16 weeks for year 3, and then every 24 weeks for year 4.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Evan Jacob Lipson

  • Primary ID J1866
  • Secondary IDs NCI-2018-03187, IRB00166274, CRMS-69243
  • Clinicaltrials.gov ID NCT03521830