Neoadjuvant and Adjuvant Anti-PD1 or Combinations for Locoregionally Advanced Melanoma
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Melanoma Stage III
- Sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- Pathologic Major Response (pMR)
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
The purpose of this study is to determine if neoadjuvant (treatment before surgery) immunotherapy treatment based on tumor biomarkers results in better participant outcomes. Immunotherapy is the treatment of disease by using a person's own immune system.
This study is divided into 2 sub-studies/parts designated Part 1 and Part 2 that will enroll in sequence starting with Part 1 followed by Part 2.
Investigators
Eligibility Criteria
Inclusion Criteria
- •This study is divided into 2 sub-studies/parts designated Part 1 and Part 2 that will enroll in sequence starting with Part 1 followed by Part
- •In Part 2, Part 2 Cohort A and Part 2 Cohort B will enroll simultaneously. Inclusion criteria apply to Part 1 and Part 2 unless otherwise specified.
- •Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study-specific procedures.
- •18 years of age or older
- •Histologic diagnosis of melanoma (cutaneous, acral, mucosal or unknown primary) belonging to the following American Joint Committee on Cancer (AJCC) 8th edition TNM stages (Tx or T1-4) and (N1b, N1c, N2b, N2c, N3b or N3c) and/or (M1a).
- •Requirements for prior systemic therapy for melanoma are as follows:
- •Sub-study Part 1: No prior systemic therapy for melanoma (N=30).
- •Sub-study Part 2 Cohort A: No prior systemic therapy for melanoma (N=20)
- •Sub-study Part 2 Cohort B: Locoregionally advanced melanoma that is refractory to systemic adjuvant therapy (anti-PD1-based or BRAF-MEK inhibitors) (N=40).
- •This excludes patients who previously received adjuvant or neoadjuvant anti-PD1 plus anti-LAG3 or anti-PD1 plus anti-CTLA
Exclusion Criteria
- •Pregnancy or lactation.
- •Treatment with another investigational drug or other systemic intervention for melanoma within 4 weeks of initiation of study drugs. Patients must not have radiotherapy within the preceding 2 weeks. Patients must have recovered from adverse events due to agents administered more than 4 weeks earlier.
- •Participants must be at least 4 weeks from major surgery and have fully recovered from any effects of surgery and be free of significant detectable infection.
- •Ocular or uveal melanoma.
- •Bowel obstruction or impending bowel obstruction within the past 3 months.
- •Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure or serious uncontrolled cardiac arrhythmia requiring medication.
- •Active or history of brain metastases or leptomeningeal metastases.
- •Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment, i.e., patients with a history of prior malignancy are eligible if treatment was completed at least 2 years before the first dose of study treatment and the patient has no evidence of disease. Participants with history of prior early-stage basal/squamous cell skin cancer, low-risk prostate cancer eligible for active surveillance or noninvasive or in situ cancers who have undergone definitive treatment at any time are also eligible.
- •Treatment with one of the following classes of drugs within the delineated time window prior to C1D1:
- •Cytotoxic, targeted therapy or other investigational therapy within 3 weeks.
Arms & Interventions
Part 1, Arm A: Nivolumab
PD-L1 positive patients will be given Nivolumab 480 mg I.V. over 30 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for 2 a total of 2 cycles.
Intervention: Nivolumab
Part 1, Arm B: Nivolumab- Relatlimab-rmbw
PD-L1 negative patients will be given a combination of Nivolumab 480 mg with Relatlimab 160 mg I.V. over 60 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for a total of 2 cycles.
Intervention: Nivolumab + Relatlimab
Part 1, Arm C: Nivolumab plus ipilimumab
PD-L1 negative patients will be given 3 mg/kg of Nivolumab plus 1 mg/kg of Ipilimumab I.V. each given over 30 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for a total of 2 cycles.
Intervention: Nivolumab
Part 1, Arm C: Nivolumab plus ipilimumab
PD-L1 negative patients will be given 3 mg/kg of Nivolumab plus 1 mg/kg of Ipilimumab I.V. each given over 30 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for a total of 2 cycles.
Intervention: Ipilimumab
Part 2, Arm A: Ipilimumab + Nivolumab-Relatimab-rmbw
Systemic therapy naïve locoregionally advanced melanoma patients will be given the fixed dose combination of 480 mg of nivolumab with 160 mg of relatlimab I.V. over 60 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for a total of 2 cycles. In addition, a single dose of 1 mg/kg ipilimumab I.V. will be given on C1D1.
Intervention: Nivolumab + Relatlimab
Part 2, Arm A: Ipilimumab + Nivolumab-Relatimab-rmbw
Systemic therapy naïve locoregionally advanced melanoma patients will be given the fixed dose combination of 480 mg of nivolumab with 160 mg of relatlimab I.V. over 60 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for a total of 2 cycles. In addition, a single dose of 1 mg/kg ipilimumab I.V. will be given on C1D1.
Intervention: Ipilimumab
Part 2, Arm B1: Triplet Combination Therapy Ipilmumab + Nivolumab-Relatlimab-rmbw
Patients with locoregionally advanced melanoma that is refractory to systemic adjuvant therapy will be given the fixed dose combination of 480 mg of nivolumab with 160 mg or relatlimab I.V. over 60 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for a total of 2 cycles. In addition, a single dose of 1 mg/kg ipilimumab I.V. will be given on C1D1.
Intervention: Nivolumab + Relatlimab
Part 2, Arm B1: Triplet Combination Therapy Ipilmumab + Nivolumab-Relatlimab-rmbw
Patients with locoregionally advanced melanoma that is refractory to systemic adjuvant therapy will be given the fixed dose combination of 480 mg of nivolumab with 160 mg or relatlimab I.V. over 60 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for a total of 2 cycles. In addition, a single dose of 1 mg/kg ipilimumab I.V. will be given on C1D1.
Intervention: Ipilimumab
Part 2, Arm B2: Doublet Combination Therapy Nivolumab-Relatlimab-rmbw
Patients with locoregionally advanced melanoma that is refractory to systemic adjuvant therapy will be given the fixed dose combination of 480 mg of nivolumab with 160 mg of relatlimab I.V. over 60 minutes (-/+ 10 minutes) every 4 weeks (every cycle) for a total of 2 cycles.
Intervention: Nivolumab + Relatlimab
Outcomes
Primary Outcomes
Pathologic Major Response (pMR)
Time Frame: Up to 36 Months
The pathologic response rate will be measured by evaluation of the residual viable tumor (RVT). Pathologic Major Response (pMR) is defined as near complete response (pCR) measured as ≤10% RVT + complete response (pCR) measured as 0% RVT.
Secondary Outcomes
- Preoperative Radiologic Response Rate(Up to 8 Weeks)
- Complete Pathologic Response Rate (pCR)(Up to 36 Months)
- Partial Pathologic Response Rate (pPR)(Up to 36 Months)
- Progression Free Survival (PFS)(Up to 36 Months)
- Overall Survival (OS)(Up to 36 Months)
- Non-Response Pathologic Response Rate (pNR)(Up to 36 Months)