The following clinical trials represent a selection of key studies currently recruiting patients with melanoma for inclusion in investigations of new therapies and new regimens of existing treatments for the disease. Each clinical trial description includes the NLM Identifier to be used as a reference with ClinicalTrials.gov. This information can help oncology practice managers and providers direct eligible patients to one of these clinical trials.
1. Adjuvant Immunotherapy plus Relatlimab and Nivolumab Fixed-Dose Combination versus Nivolumab Monotherapy in Resected Stage III-IV Melanoma
The purpose of this randomized, double-blind, parallel, phase 3 study is to assess the efficacy and safety of adjuvant immunotherapy plus relatlimab and nivolumab (Opdualag) fixed-dose combination versus nivolumab (Opdivo) monotherapy after complete resection of stage III-IV melanoma. Patients aged ≥18 years with stage IIIA (>1-mm tumor in lymph node)/B/C/D or stage IV melanoma that is completely surgically resected with negative margins within 12 weeks before randomization, who have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1, and who have been deemed disease-free by a complete physician examination within 14 days or imaging studies within 35 days prior to randomization may be eligible if other criteria are met. Eligible patients will be randomized to receive either relatlimab plus nivolumab fixed-dose combination or nivolumab monotherapy.
The primary outcome measure is recurrence-free survival time per investigator assessment up to 56 months. Secondary outcome measures include distant metastasis-free survival; overall survival (OS); incidence and severity of adverse events (AEs), including AEs leading to discontinuation, immune-mediated AEs, and drug-related AEs; incidence of clinically significant changes in hematologic and chemistry tests; and duration of treatment on next-line therapies. The study plans to enroll 1050 participants throughout the United States and worldwide. For more information, contact the BMS Study Connect Contact Center (www.bmsstudyconnect.com) at 1-855-907-3286 or
2. Encorafenib, Binimetinib, and Pembrolizumab Combination in Advanced or Metastatic Melanoma
The purpose of this randomized, double-blind, parallel, phase 3 study is to evaluate the efficacy, safety, and tolerability of combining encorafenib (Braftovi), binimetinib (Mektovi), and pembrolizumab (Keytruda) versus pembrolizumab plus placebo in the treatment of melanoma that is either advanced or metastatic, is BRAF mutation-positive, and/or is previously untreated. Patients aged ≥18 years with histologically confirmed unresectable or metastatic cutaneous melanoma with ≥1 measurable lesions according to RECIST version 1.1, who have an ECOG performance status of 0 or 1, who have documented evidence of a BRAFV600E or BRAFV600K mutation in melanoma tumor tissue, and who have not received previous first-line systemic therapy may be eligible if other criteria are met. Eligible patients will be randomized in a 1:1 ratio to receive pembrolizumab once every 3 weeks either with placebo or encorafenib and binimetinib daily.
The primary outcome measures are the incidence of dose-limiting toxicities in the safety lead-in portion of the trial (first 2 cycles of treatment), and progression-free survival (PFS) from the date of randomization to the date of first documented disease progression as determined by blinded independent central review assessment or death due to any cause, whichever occurs first. Secondary outcome measures include the incidence and severity of AEs, the objective response rate (ORR), the disease control rate (DCR), and time to response from date of first dose to the date of first documented response in the safety lead-in and phase 3 portion of the study. Other secondary measures include OS, PFS, duration of response (DOR), and changes in patient baseline. The study plans to enroll 624 participants throughout the United States and worldwide. For more information, contact the Pfizer CT.gov Call Center at 1-800-718-1021 or
3. Neoadjuvant Ipilimumab plus Nivolumab versus Adjuvant Nivolumab in Macroscopic Stage III Melanoma
The purpose of this randomized, open-label, 2-arm, multicenter phase 3 study is to evaluate the safety and efficacy of neoadjuvant ipilimumab (Yervoy) plus nivolumab (Opdivo) versus standard adjuvant nivolumab in the treatment of patients with macroscopic stage III melanoma. Patients aged ≥16 years with cytologically or histologically confirmed resectable stage III melanoma of cutaneous or unknown primary origin with ≥1 macroscopic lymph node metastases that can be biopsied, who have a World Health Organization performance status of 0 or 1, who have not received previous immunotherapy or targeted therapy, who have not received immunosuppressive medications within 6 months of study inclusion, and who have no other malignancies, except those adequately treated and with a cancer-related life expectancy >5 years, may be eligible if other criteria are met. Eligible patients will be randomized to receive either neoadjuvant ipilimumab plus nivolumab every 3 weeks followed by total lymph node dissection, or standard upfront total lymph node dissection followed by 12 cycles of nivolumab every 4 weeks.
The primary outcome measure is the comparison of event-free survival in the neoadjuvant and adjuvant group, defined as time from randomization to melanoma progression, recurrence, treatment-related death, or melanoma-related death, whichever occurs first. Secondary outcome measures include recurrence-free survival, distant metastases-free survival, OS, pathologic response rate in the neoadjuvant arm, rate and duration of immune-related AEs, evaluation of health-related quality of life in both treatment arms, and cost-effectiveness analysis in comparing the neoadjuvant arm with the standard adjuvant arm. The study plans to enroll 420 participants throughout the United States and worldwide. For more information, contact Christian Blank, MD, PhD, at
4. HBI-8000 plus Nivolumab versus Nivolumab Monotherapy in Advanced Melanoma
The purpose of this multicenter, randomized, double-blind, placebo-controlled, phase 3 study is to compare the efficacy and safety of HBI-8000, a small molecule inhibitor of class 1 histone deacetylase, versus placebo combined with nivolumab (Opdivo) in patients with unresectable or metastatic melanoma. Patients aged ≥12 years with a histopathologically confirmed diagnosis of non-uveal, stage III, or stage IV melanoma, who have >1 measurable lesion defined by RECIST version 1.1, who have an ECOG performance status of ≤1 (if aged ≥18 years) or Lansky performance score of ≥80% (if aged 12-17 years), and who have not received anti–PD-1, anti–PD-L1, or systemic therapy for unresectable or metastatic melanoma may be eligible if other criteria are met. Eligible patients will be randomized in a 1:1 ratio to receive either HBI-8000 on day 1 and continue every 3 to 4 days twice weekly or placebo plus nivolumab on day 1 of each 28-day cycle.
The primary outcome measures are ORR, defined as the percentage of patients enrolled in each study arm with a best response of complete response or partial response according to RECIST version 1.1, and PFS, defined as time from date of randomization to the first date of documented disease progression or death due to any cause, whichever occurs first. Secondary outcome measures include OS from date of randomization to death due to any cause and incidence of AEs, severity, causal relationship assessment, and outcomes of reported AEs. Other outcome measures include DOR and DCR. The study plans to enroll 480 participants throughout the United States and worldwide. For more information, contact M. Tawashi at 1-858-209-1695 or
5. 1-cm-Wide versus 2-cm-Wide Surgical Excision Margin in Stage II Primary Invasive Cutaneous Melanomas
The purpose of this randomized, parallel, multicenter, phase 3 study is to evaluate the difference in disease-free survival (DFS) rates for patients with primary cutaneous melanoma with Breslow thickness >2 mm or 1 to 2 mm with ulceration treated with either a 1-cm-wide excision margin or a 2-cm excision margin. Patients aged ≥18 years with stage II primary invasive cutaneous melanoma with Breslow thickness >2 mm without ulceration or >1 mm with ulceration, who have an uninterrupted 2-cm-wide margin around biopsy scar or primary melanoma, who have an ECOG performance status of 0 or 1, and who have a life expectancy of >5 years from time of diagnosis may be eligible if other criteria are met. Eligible patients will be randomized to receive either a 1-cm-wide local excision margin or 2-cm-wide local excision margin, followed by sentinel lymph node biopsy with or without reconstruction.
The primary outcome measure is DFS from time to randomization to clinically, histologically, or radiologically confirmed recurrence of melanoma. Secondary outcome measures include local recurrence, distant DFS, melanoma-specific survival, OS, melanoma-specific quality of life, neuropathic pain measured by PainDetect questionnaire, AEs, and surgery-related AEs. The study plans to enroll 2998 participants throughout the United States and worldwide. For more information, contact the Melanoma and Skin Cancer Trials Coordinator at
6. Nivolumab plus Ipilimumab with or without Sargramostim in Unresectable Stage III-IV Melanoma
The purpose of this randomized, parallel, phase 2/3 study is to evaluate the safety and efficacy of nivolumab (Opdivo) plus ipilimumab (Yervoy) with or without sargramostim (Leukine), a colony-stimulating factor, in the treatment of patients with stage III-IV unresectable melanoma. Patients aged ≥18 years with histologically or cytologically confirmed metastatic or unresectable melanoma; who have a known BRAF mutation status of tumor prior to randomization; who have had previous systemic therapy in the adjuvant setting; who have an ECOG performance status of 0 or 1; and who have discontinued chemotherapy, immunotherapy, or other investigational agents in the adjuvant setting ≥4 weeks before randomization may be eligible if other criteria are met. Eligible patients will be randomized to receive either nivolumab, ipilimumab, and sargramostim as induction therapy, followed by nivolumab and sargramostim as maintenance therapy; or nivolumab plus ipilimumab as induction therapy, followed by nivolumab as maintenance therapy.
The primary outcome measure is OS between the 2 arms from the time of randomization to death from any cause, assessed up to 5 years. Secondary outcome measures include PFS, incidence of toxicities, immune-related response, and standard response criteria based on RECIST version 1.1. The study plans to enroll 600 participants throughout the United States and worldwide. For more information, contact the recruiting sites directly. The NLM identifier is NCT02339571.
7. Intratumoral CMP-001 with or without Nivolumab in Unresectable or Metastatic Melanoma
The purpose of this randomized, open-label, active-control, phase 2/3 study is to evaluate the safety and efficacy of first-line CMP-001 (Vidutolimod), a CpG-A toll-like receptor 9 agonist, in combination with nivolumab (Opdivo) versus nivolumab monotherapy in patients with unresectable or metastatic melanoma. Patients aged ≥18 years with histologically or cytologically confirmed unresectable stage III or stage IV melanoma with measurable disease as per RECIST version 1.1 with >1 accessible lesion amenable to repeated intratumoral injection or lesion ≥1 cm in diameter that can be followed as target lesions per RECIST version 1.1, who have adequate organ function based on lab values within 3 weeks before the first dose of study treatment on week 1 day 1, and who have an ECOG performance status of 0 to 1 may be eligible if other criteria are met. Eligible patients will be randomized to receive CMP-001 weekly for 7 doses followed by CMP-001 every 3 weeks plus nivolumab every 3 weeks, or nivolumab monotherapy every 3 weeks.
The primary outcome measures include confirmed ORR and PFS in the combination arm versus the monotherapy arm from date of randomization until 30 days after last CMP-001 injection. Secondary outcome measures include the incidence of AEs, serious AEs, and AEs leading to discontinuation or death; OS; confirmed ORR; DOR; DCR; treatment response in noninjected target lesions; and immune PFS, DOR, and ORR. The study plans to enroll 450 participants throughout the United States. For more information, contact the Checkmate Medical Monitor at 1-617-682-3625 or