Justin Moser, MD, is a medical oncologist at HonorHealth and an associate clinical investigator at HonorHealth Research Institute.

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In today’s episode, supported by Immatics, we had the pleasure of speaking with Justin Moser, MD, about the ongoing phase 3 SUPRAME trial (NCT06743126) investigating the PRAME-directed T-cell receptor T-cell therapy IMA203 vs treatment of physician's choice in patients with previously treated, unresectable or metastatic cutaneous melanoma. Dr Moser is an associate clinical investigator, a melanoma and cutaneous oncology specialist, and a phase 1 trialist at HonorHealth Research Institute in Scottsdale, Arizona; as well as a research associate professor at the Arizona State University School of Medicine and Advanced Medical Engineering.

In our exclusive interview, Dr Moser discussed the unique mechanism of action of IMA203, previously reported phase 1 data with this agent in patients with melanoma, and the design and potential future implications of SUPRAME. 

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Podcasts

Justin Moser, MD, discusses the ongoing phase 3 SUPRAME trial investigating IMA203 in previously treated, unresectable or metastatic cutaneous melanoma. 

IMA203 Emerges as a Novel Investigational Agent in Cutaneous Melanoma: With Justin Moser, MD

Dr Moser on the SUPRAME Trial of IMA203 in Pretreated Cutaneous Melanoma

"This is a registrational randomized study, so if this study were to be positive, showing that the progression-free survival for patients treated with IMA203 is better than that of the investigator's choice [of therapy], this would hopefully lead to FDA approval."

Justin Moser, MD, a medical oncologist at HonorHealth and associate clinical investigator at HonorHealth Research Institute, detailed the design and potential implications of the phase 3 SUPRAME trial (NCT06743126), a registrational study evaluating the efficacy, safety, and tolerability of the autologous T-cell receptor (TCR) therapy IMA203 in patients with previously treated advanced cutaneous melanoma.

This open-label, multicenter, randomized trial is enrolling patients with unresectable or metastatic cutaneous melanoma who have progressed on prior immune checkpoint inhibitor therapy, Moser began. All patients must be HLA-A*02:01 positive, have measurable disease per RECIST 1.1 criteria, ECOG performance status of 0 or 1, and adequate organ function. 

Following HLA testing and leukapheresis, patients are randomized to receive either IMA203 or investigator’s choice of standard therapy, which may include checkpoint inhibitors, lifileucel (Amtagvi) in the United States, or chemotherapy. Those assigned to the IMA203 arm will receive a lymphodepletion regimen consisting of fludarabine and cyclophosphamide, followed by a one-time infusion of IMA203 and subsequent low-dose IL-2. Patients will be stratified according to geography, baseline lactate dehydrogenase levels, and disease stage.

The trial’s primary end point is progression-free survival. Key secondary end points include overall survival, objective response rate, safety, and patient-reported quality of life. The trial is currently open to enrollment and is being conducted across approximately 50 sites in the United States and Europe.

According to Moser, the SUPRAME trial could change the treatment landscape for patients with refractory cutaneous melanoma who are HLA-A*02:01 positive. If positive, the trial could support FDA approval of IMA203, allowing it to be integrated as a new standard of care in this biomarker-defined population.

Videos

Justin Moser, MD, discusses the design and implications of the SUPRAME trial investigating IMA203 in pretreated advanced cutaneous melanoma.

Dr Moser on Treatment Considerations After Progression on Frontline PD-1 Inhibitors in Melanoma

"One of the challenges we have in melanoma is that the vast majority…of FDA-approved treatments that are still clinically relevant today are approved in the frontline setting. [Therefore, it’s hard to know what the best option is for [a patient in the] second-line. [However], based on retrospective data, it looks like the chance of [a patient] benefiting from a second-line checkpoint inhibitor–based combination depends on how well they responded in the first line."

Justin Moser, MD, a medical oncologist at HonorHealth and an associate clinical investigator at HonorHealth Research Institute, discussed therapeutic decision-making for patients with advanced melanoma who progress following initial treatment with checkpoint inhibitor–based combinations, such as nivolumab (Opdivo) plus ipilimumab (Yervoy) or nivolumab plus relatlimab-rmbw (Opdualag).

A major clinical challenge in this setting is that most FDA-approved regimens are indicated in the frontline setting, leaving limited guidance or prospective data to inform second-line strategies, Moser began. For patients without a 

 mutation, the most accessible second-line options remain other checkpoint inhibitor combinations, Moser stated. However, the utility of these regimens is highly dependent on the patient’s initial response to immunotherapy, Moser stated.

Retrospective data suggest that patients who achieve a clinical benefit—such as partial response, complete response, or prolonged disease stability—before developing resistance to first-line checkpoint blockade have an approximately 30% to 33% chance of responding to a different checkpoint combination in the second-line setting, Moser stated. In these cases, re-challenging with another immunotherapy combination may be reasonable, particularly if the initial benefit was durable, Moser stated.

In contrast, for patients with primary resistance to frontline checkpoint inhibition—defined as no clinical benefit or early progression—the likelihood of response to a subsequent immunotherapy-based approach is low, likely under 10%, Moser stated. For these patients, non–checkpoint inhibitor–based strategies may be more appropriate, including clinical trial enrollment or other agents with alternative mechanisms of action, Moser stated.

Evaluating how a patient responded to their initial therapy is essential when determining appropriate next steps, Moser stated. He emphasized the need for prospective studies to better guide post–checkpoint inhibitor treatment, particularly for patients without actionable mutations, and underscored the importance of ongoing research to address resistance and expand second-line options for this population.

Although checkpoint inhibitors have transformed melanoma treatment, patients with dual checkpoint inhibitor–refractory disease are unlikely to benefit from additional checkpoint-based therapies, Moser stated. If patients responded to a prior checkpoint inhibitor and maintained benefit, re-challenge may be reasonable; otherwise, alternative strategies are needed, Moser asserted. Novel immune approaches, including cell therapies like tumor-infiltrating lymphocytes and investigational cytokines with improved delivery mechanisms, are showing early promise in phase 1 trials and may soon expand available options, Moser concluded.

Justin Moser, MD, discusses key considerations for second-line treatment selection for patients with melanoma who have progressed on PD-1 inhibitors.

Justin Moser, MD

Articles

IMA203 Emerges as a Novel Investigational Agent in Cutaneous Melanoma: With Justin Moser, MD

Dr Moser on the SUPRAME Trial of IMA203 in Pretreated Cutaneous Melanoma

Dr Moser on Treatment Considerations After Progression on Frontline PD-1 Inhibitors in Melanoma