Melanoma Clinical Trials

1.      Neoadjuvant

a.      Neoadjuvant PD-1 blockade in patients with stage IIB/C melanoma (2022-0627) (NCT03757689)
Principal Investigator: Jeffrey Gershenwald, M.D.
This study aims to assess the rate of positive sentinel lymph nodes (SLNs, the closest draining lymph node(s) to the primary melanoma site) and whether pre-surgical pembrolizumab reduces SLN positivity in Stage IIB/C melanoma. Patients will receive one dose of pembrolizumab (200 mg), followed by wide excision and SLN biopsy about 3 weeks later. Post-operatively, subjects will receive up to 1 year of adjuvant pembrolizumab 200 mg every 3 weeks.

b.      Neoadjuvant immune checkpoint blockade + a prebiotic food-enriched dietary intervention to optimize immune response in melanoma: NEO-PreFED (2024-0388) (NCT06548789)
Principal Investigator: Jennifer McQuade, M.D.

This study determines the feasibility, compliance, and adherence to the Prebiotic Food-enriched Diet (PreFED) intervention in resectable melanoma patients initiating neoadjuvant Ipi/Nivo.

c.      A phase 2 and phase 3 peri-operative trial of Fianlimab and Cemiplimab compared with anti-PD1 alone in patients with resectable stage III and IV melanoma  (2024-1021) (NCT06190951)

Principal Investigator: Rodabe Amaria, M.D.

This study tests the experimental drug fianlimab (REGN3767) combined with cemiplimab versus the approved drug pembrolizumab as peri-operative therapy in high-risk melanoma. It aims to evaluate treatment effectiveness, side effects, drug levels in the blood, the development of anti-drug antibodies, and potential impacts on quality of life.

2.      Adjuvant

Alliance A091903: A randomized phase II trial of adjuvant Nivolumab with or without Cabozantinib in patients with resected mucosal melanoma (2023-0350 ). (NCT05111574)
Principal Investigator: Jennifer McQuade, M.D.
This phase II trial tests whether nivolumab in combination with cabozantinib works in patients with mucosal melanoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps stop the spread of tumor cells. Giving nivolumab in combination with cabozantinib could prevent cancer from returning.

3.      Patients with Previous Treatment

a.      A Phase I/Ib Study of Concurrent Intravenous and Intrathecal Nivolumab for Patients with Leptomeningeal Disease (LMD) (2016-0567) (NCT03025256)
Principal Investigator: Isabella Glitza, M.D.
This phase I/Ib trial studies the side effects and best dose of intrathecal nivolumab, and how well it works in combination with intravenous nivolumab in treating patients with leptomeningeal disease. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

b.      A Phase 1, Open-Label, Dose-Escalation with Expansion Study of SX-682 in Subjects with Metastatic Melanoma Concurrently Treated with Pembrolizumab (2021-0705) (NCT03161431)
Principal Investigator: Hussein Tawbi, M.D., Ph.D.
Cancers attract myeloid-derived suppressor cells (MDSCs) that prevent our own immune responses from destroying the cancer. This study will be the first to begin to determine if the newly discovered drug SX-682 can block cancers from attracting MDSCs. This first study will enroll participants with melanoma, as melanoma cancer has been shown to be able to attract MDSCs. The study will begin to determine if SX-682 is a safe and effective treatment for melanoma. It is thought that SX-682 will block MDSCs from going to the cancer, and thus will allow a patient's own immune system to attack the cancer. The first participants enrolled in the study will receive for 21 days SX-682 as monotherapy. After 21 days, participants will receive pembrolizumab therapy (an approved immunotherapy for melanoma) in combination with SX-682 for up to approximately 2 years. Once the safe dose level of SX-682 in combination with pembrolizumab is determined, the remaining participants will be enrolled at the highest safe dose level of SX-682, in combination with pembrolizumab. These participants will receive the combination therapy and be evaluated in the study for approximately 2 years.

c.      A Phase 1/1b, First-In-Human, Multi-Part, Open-Label, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of DF6002 as a Monotherapy and in Combination With Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumors, and Expansion in Selected Indications (2020-0916) (NCT04423029)
Principal Investigator: Hussein Tawbi, M.D., Ph.D.
The purpose of this study is to evaluate the safety, tolerability, drug-levels, drug-effects and preliminary anti-tumor activity of DF6002 alone and in combination with Nivolumab in participants with advanced solid tumors.

d.      A phase 1 first-in-human study to investigate the safety, efficacy, pharmacokinetics, and pharmacodynamic activity of CLN-617 alone and in combination with Pembrolizumab in patients with advanced solid tumors (2023-0517) (NCT06035744)
Principal Investigator: Alexandra Ikeguchi, M.D.
CLN-617-001 is a Phase 1, open-label, dose escalation, dose optimization, and dose expansion study of CLN-617 alone and in combination with Pembrolizumab in patients with advanced solid tumors

e.      A phase 1/2 study of KSQ-001EX, autologous tumor-infiltrating lymphocytes engineered to inactivate the SOCS1 gene, in patients with select advanced solid tumors (2023-0571) (NCT06237881)
Principal Investigator: Rodabe Amaria, M.D.
To learn if KSQ-001EX is safe to give to participants with advanced forms of solid tumors.

f.        Impact of a prebiotic food-enriched diet (PreFED) in combination with Ipilimumab/Nivolumab combination immune checkpoint blockade (ICB) in ICB-refractory melanoma patients (2023-1067) (NCT06250335)
Principal Investigator: Jennifer McQuade, M.D.
To learn about the possible effects of a prebiotic food-enriched diet (PreFED) targeting the gut microbiome in participants with ICI-refractory melanoma who are receiving the combination of ipilimumab and nivolumab as part of their standard care.

g.      Phase 1 dose escalation and expansion study of PRAME T cell receptor (TCR) engineered NK cells in patients with recurrent and/or refractory melanoma (PRAMETIME-Mel) (2024-0365) (NCT06660420)
Principal Investigator: Isabella Glitza, M.D.
To find the highest tolerable dose and recommended dose of PRAME-TCR-NK cells that can be given to participants with recurrent and/or refractory melanoma. The safety and tolerability of PRAME-TCR-NK cells will also be studied.

h.      A phase 1/2 study of KSQ-004EX, autologous tumor infiltrating lymphocytes engineered to inactivate genes encoding SOCS1 and Regnase-1, in patients with select advanced solid tumors (2024-0397) (NCT06598371)
Principal Investigator: Rodabe Amaria, M.D.
Phase 1 is to find the recommended dose of KSQ-004EX to give to participants with advanced solid tumors. Phase 2 is to learn if KSQ-004EX at the recommended dose found in Phase1 can help to control advanced solid tumors. The safety and effects of KSQ-004EX will also be studied in both phases.

i.        A phase 1/2a, open-label, dose-escalation and dose-expansion first-in-human study of the safety, tolerability, activity, and pharmacokinetics of REGN10597 (anti PD-1-IL2RA-IL2 fusion protein) in patients with advanced solid organ malignancies (2024-0527) (NCT06413680)
Principal Investigator: Rodabe Amaria, M.D.
This study is researching an experimental drug called REGN10597 (called "study drug"). The study is focused on patients with certain solid tumors that are in an advanced stage. The aim of the study is to see how safe, tolerable, and effective the study drug is. The study is looking at several other research questions, including: what side effects may happen from taking the study drug, how much study drug is in the blood at different times, whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects

j.        A prospective, multicenter, open-label, randomized, actively controlled, parallel-group phase 3 clinical trial to evaluate efficacy, safety, and tolerability of IMA203 versus investigator's choice of treatment in patients with previously treated, unresectable or metastatic cutaneous melanoma (ACTengine IMA203-301) (2024-1770) (NCT06743126)
Principal Investigator: Rodabe Amaria, M.D.
This clinical trial is a prospective, multicenter, open-label, randomized, actively controlled, parallel-group Phase 3 clinical trial to evaluate the efficacy, safety and tolerability of treatment with IMA203 administered at the recommended phase 2 dose versus investigator's choice of treatment in patients with previously treated, unresectable or metastatic cutaneous melanoma

4.      Treatment Naïve

a.      A Phase I/Ib Study of Concurrent Intravenous and Intrathecal Nivolumab for Patients with Leptomeningeal Disease (LMD) (2016-0567) (NCT03025256)
Principal Investigator: Isabella Glitza, M.D.
This phase I/Ib trial studies the side effects and best dose of intrathecal nivolumab, and how well it works in combination with intravenous nivolumab in treating patients with leptomeningeal disease. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

b.         Phase II Study of Binimetinib with Encorafenib in Patients with Metastatic Melanoma and CNS metastases (2021-0205). (NCT05026983)
Principal Investigator: Isabella C. Glitza, M.D.
The goal of this clinical research study is to learn if the combination of encorafenib and binimetinib can help to control melanoma brain metastasis (melanoma that has spread to the brain) or leptomeningeal disease (LMD, when the cancer has spread to the lining of the brain) that has a genetic mutation (change) called BRAFV600. The safety of these drugs will also be studied.

c.         Phase II study of Nivolumab in combination with Relatlimab in patients with active Melanoma brain metastases (2021-1203). (NCT05704647)
Principle Investigator: Hussein Tawbi, M.D.
The goal of the study is to learn if giving nivolumab in combination with relatlimab can help to control melanoma that has spread to the brain (melanoma with brain metastases). The safety and side effects of the study drug combination will also be studied.

d.         Alliance A091903: A randomized phase II trial of adjuvant Nivolumab with or without Cabozantinib in patients with resected mucosal melanoma (2023-0350). (NCT05111574)
Principal Investigator: Jennifer McQuade, M.D.
This phase II trial tests whether nivolumab in combination with cabozantinib works in patients with mucosal melanoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps stop the spread of tumor cells. Giving nivolumab in combination with cabozantinib could prevent cancer from returning.

e.      A phase 3 study of fixed dose combinations of Fianlimab and Cemiplimab versus Relatlimab and Nivolumab in participants with unresectable or metastatic melanoma (2024-0401) (NCT06246916)
Principal Investigator: Hussein Tawbi, M.D., Ph.D.
This study is researching an experimental drug called fianlimab (also known as REGN3767), combined with another medication called cemiplimab (also known as REGN2810), called "study drugs". The study is focused on patients with a type of skin cancer known as melanoma. The aim of the study is to see how safe and effective the combination of fianlimab and cemiplimab is in treating melanoma, in comparison with the combination of two medications, relatlimab and nivolumab, commercialized under the brand name Opdualag™ and approved for the treatment of melanoma in adults and children. The study is looking at several other research questions, including: - What side effects may happen from taking the study drugs. - How much study drug is in the blood at different times. - Whether the body makes antibodies against the study drugs (which could make the drug less effective or could lead to side effects)

f.        Phase I/IIa dose finding study of Triplet regimen of Relatlimab Ipilimumab and Nivolumab in first line therapy of metastatic melanoma (TRINITY) (2024-1032) (NCT06683755)
Principal Investigator: Hussein Tawbi, M.D., Ph.D.
To determine the recommended Phase IIa dose (RP2D) of the triplet combination. To determine the safety and efficacy of the combination at the RP2D.

5.      Patients with Uveal Melanoma

a.         Phase II study of Nivolumab in combination with Relatlimab in patients with active Melanoma brain metastases (2021-1203). (NCT05704647)
Principle Investigator: Hussein Tawbi, M.D.
The goal of the study is to learn if giving nivolumab in combination with relatlimab can help to control melanoma that has spread to the brain (melanoma with brain metastases). The safety and side effects of the study drug combination will also be studied.

b.         IDE196 (Darovasertib) in combination with Crizotinib versus investigator's choice of treatment as first-line therapy in hla-a2 negative metastatic uveal melanoma (dar-um-2) (2023-0582). (NCT05987332)
Principal Investigator: Alexandra Ikeguchi, M.D.
This is a Phase 2/3, multi-arm, multi-stage, open-label study of human leukocyte antigen (HLA)-A*02:01 negative participants with metastatic uveal melanoma (MUM) who will be randomized to receive either IDE196 + crizotinib or investigator's choice of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine).

c.      A randomized, phase 2/3, open-label study to investigate the efficacy and safety of RP2 in combination with nivolumab versus ipilimumab in combination with nivolumab in immune checkpoint inhibitor-naive adult patients with metastatic uveal melanoma (2024-1495) (NCT06581406)
Principal Investigator: Alexandra Ikeguchi, M.D.
The purpose of this study is to measure the clinical benefits of the combination of RP2 and nivolumab as compared with the combination of nivolumab and ipilimumab in patients with metastatic uveal melanoma who have not been treated with immune checkpoint inhibitor therapy.

6.      Patients with Non-Melanoma Skin Cancers

a.      A phase 1 first-in-human study to investigate the safety, efficacy, pharmacokinetics, and pharmacodynamic activity of CLN-617 alone and in combination with Pembrolizumab in patients with advanced solid tumors (2023-0517) (NCT06035744)
Principal Investigator: Alexandra Ikeguchi, M.D.
CLN-617-001 is a Phase 1, open-label, dose escalation, dose optimization and dose expansion study of CLN-617 alone and in combination with Pembrolizumab in patients with advanced solid tumors