Clinical Trial 23377

• Overview

  Study Title:

  A Phase 3 Study of Fixed Dose Combinations of Fianlimab and Cemiplimab versus Relatlimab and Nivolumab in Participants with Unresectable or Metastatic Melanoma.

  Objective:

  Primary Objectives To demonstrate superiority of Arm A (fianlimab + cemiplimab) compared to Arm B (Opdualag) as measured by objective response rate (ORR) To describe progression-free survival (PFS) in Arm A and Arm B To describe overall survival (OS) in Arm A and Arm B

• Treatments

  Therapies:

  Immunotherapy

  Medications:

  BMS-936558 (Nivolumab); BMS-986016 (Relatlimab); Cemiplimab (); Fianlimab (); Nivolumab (Opdivo); REGN2810 (Cemiplimab); Relatlimab ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Age ≥18 years on the date of providing informed consent.
  • Participants with histologically confirmed unresectable stage III and stage IV (metastatic) melanoma per AJCC, eighth revised edition (Amin, 2017).
  • Participants must not have received prior systemic therapy for unresectable or metastatic melanoma. a) Participants who received adjuvant and/or neoadjuvant systemic therapies are eligible if they did not have evidence of progression or recurrence of disease and/or discontinued due to occurrence of imAEs ≥ grade 3 while on such therapies. Also, participants must have had a treatment-free and disease-free interval of >6 months.
  • Measurable disease per RECIST version 1.1. a) Previously irradiated lesions can only be counted as target lesions if they have been demonstrated to progress and no other target lesion is available. b) Cutaneous lesions should be evaluated as non-target lesions.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.
  • Adequate bone marrow function, as determined by hematological parameters: a) Absolute neutrophil count ≥1.5 x 109 /L (1500/mm3). b) Hemoglobin ≥9.0 g/dL (5.59 mmol/L). c) Platelet count ≥75,000/mm³.
  • Adequate hepatic function, as determined by: a) Aspartate aminotransferase (AST) ≤3x upper limit of normal (ULN) (or ≤5x ULN, if liver metastases). b) Alanine aminotransferase (ALT) ≤3x ULN (or ≤5x ULN, if liver metastases). c) Alkaline phosphatase (ALP) > Adequate kidney function, as determined by creatinine clearance (CrCl) ≥30 mL/min.
  • Women of childbearing potential (WOCBP*) must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) at screening.
  • WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire study, until 6 months after the last dose of study treatment.
  • All men must agree not to donate sperm during the study and for 6 months after receiving the last dose of study treatment.
  • Willing and able to provide informed consent as specified by health authorities and institutional guidelines.
  • Willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
  • Other inclusion criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Uveal, acral or mucosal melanoma.
  • Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment.
  • Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C virus (HCV) infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection. Mild cancer-related immunodeficiency (such as immunodeficiency treated with gamma globulin and without chronic or recurrent infection) is allowed.
  • Unknown BRAF V600 mutation status. Participants with BRAF-mutated melanoma who present with symptoms of rapidly PD and are considered by investigator’s assessment as likely to benefit from upfront treatment with BRAF/MEK-inhibitors should not be enrolled in the study.
  • Another primary malignancy that is progressing or required active treatment in the past 2 years, except for those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ). Adjuvant hormonotherapy used for breast cancer or other hormone-sensitive cancers in long-term remission is allowed. No prior treatment with immune checkpoint inhibitor is allowed.
  • Pregnant or breastfeeding.
  • Continued sexual activity in WOCBP or sexually active men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose.
  • Prior immune checkpoint inhibitor therapy other than anti-PD1/PD-L1 (ie, anti-LAG3, anti-CTLA4).
  • Systemic immune suppression.
  • Participants with a history of myocarditis.
  • Troponin T (TnT) or troponin I (TnI) >2x institutional ULN. a) Participants with TnT or TnI levels between >1 to 2x ULN are permitted if repeat levels within 24 hours are ≤1x ULN. If TnT or TnI levels are >1 to 2x ULN within 24 hours, the participant may undergo a cardiac evaluation and be considered for treatment. If TnT or TnI repeat levels beyond 24 hours are > History or current evidence of significant (CTCAE grade ≥2) local or systemic infection (eg, cellulitis, abscess) or systemic infection (eg, pneumonia, septicemia) requiring systemic antibiotic treatment within 14 days prior to the first dose of study treatment.
  • Active or untreated brain metastases or spinal cord compression. Participants with leptomeningeal disease are excluded.
  • Known hypersensitivity to the active substances or to any of the excipients.
  • Presence of a severe concurrent illness or other condition (eg, psychological, family, sociological, or geographical circumstances) that does not permit adequate follow-up and compliance with the study protocol.
  • Received a live vaccine within 30 days of planned start of study treatment.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to screening.
  • Prior allogeneic stem cell transplant or solid organ transplant.
  • Any medical condition that in the opinion of the investigator would make participation in the study not in the best interest of the participant.
  • Member of the clinical site study team and/or his or her immediate family unless prior approval granted by the sponsor.
  • Participants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities will be excluded from this study.
  • Other criteria may apply

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