This is a new clinical trial using Tebentafusp alone or in combination with Pembrolizumab is now open and actively enrolling at the Orlando Health Cancer Institute for patients dealing with Metastatic Cutaneous Melanoma. Tebentafusp is currently FDA approved for all patients with Metastatic Uveal Melanoma. Detailed information can be found here at clinicaltrials.gov and NEJM
As the quest for better therapeutic options in melanoma treatment continues, a novel clinical trial has been inaugurated for patients with advanced non-ocular melanoma refractory to PD1 inhibitors. Here’s a glimpse into this exciting new avenue of therapy.
Overview of the TEBE-AM Study
The TEBE-AM study, formally titled as “Phase 2/3 Randomized Study of Tebentafusp as Monotherapy and in Combination With Pembrolizumab Versus Investigator’s Choice in HLA-A*02:01-positive Participants With Previously Treated Advanced Cutaneous Melanoma”, is a multicenter, open-label initiative aiming to evaluate the efficacy and safety of tebentafusp. This drug, designed as a soluble gp100-specific T cell receptor with anti-CD3 scFV, is under assessment both as monotherapy (Arm A) and in conjunction with pembrolizumab (Arm B). The study contrasts these interventions against a standard of care or best supportive care (Arm C).
Tebentafusp:
a novel bispecific protein built by fusing an enhanced T-cell receptor with an anti-CD3 effector, redirecting T cells to attack glycoprotein 100–positive cells, a characteristic of melanoma. A phase 3 trial, involving previously untreated HLA-A*02:01–positive Uveal Melanoma patients, compared tebentafusp against established therapies: pembrolizumab, ipilimumab, or dacarbazine. The results were promising. One year post-treatment, 73% of tebentafusp recipients were still alive, compared to 59% in the control group. Notably, progression-free survival was also superior in the tebentafusp group. Though the treatment did present with side effects, mainly cytokine-mediated and skin-related issues, these were manageable and often decreased after initial doses. This treatment is FDA approved for patients with metastatic uveal melanoma.
TEBE-AM Study Treatment Modalities in Focus
1. Monotherapy with Tebentafusp (Arm A): Tebentafusp is being administered as a single agent to test its potential against advanced melanoma.
2. Tebentafusp in Combination with Pembrolizumab (Arm B): This arm evaluates the synergistic effect of combining Tebentafusp with Pembrolizumab, an anti-PD-1 antibody.
3. Investigator’s Choice (Arm C): This includes a broad range of treatment modalities, from clinical trials of investigational agents, salvage therapies as per local standards of care, to best supportive care. We currently have 3-4 active clinical trials or compassionate programs using other forms of immunotherapies, cellular therapies or intratumoral therapies that patients can consider if randomized to this arm.
Eligibility Insights
Participants are required to be HLA-A*02:01-positive with unresectable Stage III or IV non-ocular melanoma. Other key inclusion criteria encompass the provision of a tumor tissue sample, having a disease measurable by RECIST 1.1 standards, and an ECOG performance status score of 0 or 1. Pregnant or lactating women, patients with ocular or metastatic uveal melanoma, and those with a history of certain malignancies are among the exclusions. For a comprehensive list of inclusion and exclusion criteria, interested healthcare providers should review the detailed protocol.
Recruitment & Timeline
As of September 19, 2022, the study is actively recruiting, with an estimated enrollment of 460 participants. The study is projected to conclude by September 2027, with primary data collection wrapping up by December 2026.
The TEBE-AM study is an instrumental stride in the dynamic landscape of melanoma treatments. As healthcare providers, staying abreast of such innovations ensures we deliver the most cutting-edge care to our patients. If you’re keen on exploring participation or referring patients for this trial, engagement is pivotal to advance our collective understanding and potentially bring more effective solutions for advanced melanoma to the forefront.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.