Nivolumab Alone or Plus Relatlimab or Ipilimumab for Patients With Locally-Advanced Unresectable or Metastatic Basal Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Basal Cell Carcinoma
- Sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Enrollment
- 57
- Locations
- 1
- Primary Endpoint
- Objective Response Rate
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
This is a phase 2 trial assessing the efficacy of nivolumab, alone or in combination with relatlimab or ipilimumab in treating patients with locally-advanced unresectable or metastatic basal cell carcinoma.
Detailed Description
This is an open-label, phase 2 signal-seeking study. Screening will begin by establishing a participant's initial eligibility and signing of the informed consent document. Eligible, enrolled patients will be assigned to one of 3 cohorts in a non-randomized fashion according to prior treatment history. Cohort A: Patients with advanced BCC (aBCC) who are treatment-naïve (i.e., no prior hedgehog pathway inhibitors and T cell modulating agents) will receive anti-PD-1 (Nivolumab) alone. Patients will receive Nivolumab 480mg IV every 4 weeks for up to 48 weeks (six 8-week cycles). Cohort B: Patients with advanced BCC who experience disease progression on anti-PD-1 (Nivolumab) + anti-LAG-3 (Relatlimab) will receive anti-PD-1 (Nivolumab) + anti-CTLA-4 (Ipilimumab). Patients will receive Nivolumab 240mg IV + Ipilimumab 1mg/kg IV every 3 weeks x 4 doses, then Nivolumab 480mg IV every 4 weeks x 7 doses starting 6 weeks after the final dose of Ipilimumab + Nivolumab. Cohort C: Patients with advanced BCC who experience disease progression on anti-PD-1 (on or off trial) will receive anti-PD-1 (Nivolumab) + anti-LAG-3 (Relatlimab). Patients will receive Nivolumab 480mg IV + Relatlimab 480mg IV every 4 weeks for up to 48 weeks (six 8-week cycles). Patients enrolled on Cohort A who demonstrate progressive disease after Nivolumab monotherapy may, if appropriate in the opinion of the investigator, move to Cohort B or Cohort C. Discontinuation of nivolumab or ipilimumab +nivolumab or relatlimab + nivolumab may be at the discretion of the investigator under circumstances including but not limited to the following: 1. A complete response to therapy. 2. A severe IMAR, defined as Grade 3 or greater. 3. Documented disease progression warranting alternative systemic therapy. 4. Intercurrent illness that prevents further administration of study treatment. 5. Noncompliance with trial treatment or procedure requirements, or administrative reasons.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed Written Informed Consent
- •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.
- •Type of Participant and Target Disease Characteristics
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-
- •Participants with histologically confirmed Basal Cell Carcinoma with disease that is considered by the investigator to be unresectable or metastatic.
- •i) COHORT A: Patients with advanced BCC who are treatment-naïve (i.e., no prior hedgehog pathway inhibitors and T cell modulating agents) will receive anti-PD-1 (nivolumab) alone.
- •ii) COHORT B: • Patients with advanced BCC who experience disease progression on anti-PD-1 (nivolumab) + anti-LAG-3 (relatlimab) will receive anti-PD-1 (nivolumab) + anti-CTLA-4 (ipilimumab).
- •iii) COHORT C: • Patients with advanced BCC who experience disease progression on anti-PD-1 (on or off trial) will receive anti-PD-1 (nivolumab) + anti-LAG-3 (relatlimab).
- •c. At least one measurable lesion by the RECIST 1.1 Criteria.
Exclusion Criteria
- •Medical Conditions
- •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 P.I.
- •Participants with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS).
- •Viral hepatitis.
- •i. Participants with active hepatitis B (positive hepatitis B surface antigen \[HBsAg\] or hepatitis C virus (HCV) (positive HCV RNA) are excluded.
- •ii. 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 DNA quantification must be performed and results discussed with the P.I.
- •iii. HBV carriers or those participants requiring antiviral therapy are not eligible to participate.
- •iv. 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.
Arms & Interventions
Previous Systemic Therapy Patients
Cohort A: Nivolumab 480mg IV q4weeks for up to 48 weeks (six 8-week cycles)
Intervention: Nivolumab
Progression after anti-PD-1 therapy (Cohort A) and Cohort C
Cohort B: Nivolumab 240mg IV + ipilimumab 1mg/kg IV q3 weeks x 4 doses, then nivolumab 480mg IV q4 weeks x 7 doses for up to 48 total weeks of therapy.
Intervention: Nivolumab
Progression after anti-PD-1 therapy (Cohort A) and Cohort C
Cohort B: Nivolumab 240mg IV + ipilimumab 1mg/kg IV q3 weeks x 4 doses, then nivolumab 480mg IV q4 weeks x 7 doses for up to 48 total weeks of therapy.
Intervention: Ipilimumab
Progression after anti-PD-1 therapy (Cohort A)
Cohort C: Nivolumab 480 mg IV q4 weeks plus relatlimab 480 mg IV q4 weeks for up to 48 weeks.
Intervention: Nivolumab
Progression after anti-PD-1 therapy (Cohort A)
Cohort C: Nivolumab 480 mg IV q4 weeks plus relatlimab 480 mg IV q4 weeks for up to 48 weeks.
Intervention: Relatlimab
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: 5 years
Objective response rate per the revised Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Secondary Outcomes
- progression-free survival(5 years)
- duration of response(5 years)
- overall survival(5 years)