KEY TAKEAWAYS
- The TEBE-AM phase II/III trial aimed to assess the efficacy and safety of tebentafusp in previously treated advanced non-uveal melanoma.
- The co-primary endpoints were OS and early ctDNA reduction.
Tebentafusp is a promising new drug for melanoma, including skin melanoma, as it targets a protein that is overexpressed in melanoma cells. Researchers aimed to assess the efficacy and safety of tebentafusp in previously treated advanced non-uveal melanoma.
In a pioneering trial, tebentafusp monotherapy displayed a promising 1-year overall survival (OS) of around 74% in anti-PD(L)1 naïve HLA-A*02:01+ patients(pts) with metastatic cutaneous melanoma (mCM). Subsequent Phase 1 trials combining tebentafusp with anti-PDL1, with or without anti-CTLA4, demonstrated a 1-year OS of 75% in mCM pts who had progressed on prior anti-PD(L)1 therapy, surpassing recent benchmarks (1-year OS 38%-57%) in similar patient populations. The encouraging activity of tebentafusp in both monotherapy and combination with anti-PD(L)1 agents in advanced melanoma (AM) justifies the initiation of a Phase 2/3 trial (TEBE-AM; NCT05549297) for pts who have progressed on standard-of-care therapies. In metastatic uveal melanoma (mUM) trials, RECIST response underestimated tebentafusp’s OS benefit, highlighting the importance of early reduction in circulating tumor DNA (ctDNA) levels relative to baseline. In the Phase 2 part of this study, ctDNA reduction serves as an innovative dual primary endpoint along with OS, offering an early measure of changes in tumor burden.
The study included HLA-A*02:01+ pts with non-uveal AM, having progressed on previous anti-PD(L)1, and they received prior ipilimumab and a prior BRAF/MEK inhibitor regimen if there’s an actionable BRAF mutation. Pts were randomly assigned (1:1:1) to receive tebentafusp monotherapy, tebentafusp combined with pembrolizumab, or investigator’s choice (IC). The IC arm allowed pts to enroll in investigational agent trials and receive local standard of care or best supportive care while being monitored for key endpoints.
Randomization into the Phase 3 portion will start immediately after completing accrual in the Phase 2 portion. Efficacy data from Phase 2 may influence changes to the Phase 3 design. Primary endpoints include ctDNA reduction relative to baseline and OS in Phase 2 and 3.
The phase 2 enrollment began in the US in January 2023 and is expected to open in other countries by mid-2023.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.TPS9594
Clinical Trial: https://www.clinicaltrials.gov/study/NCT05549297
Diwakar Davar, Alexandra Ikeguchi, Elizabeth Iannotti Buchbinder, Alexander Noor Shoushtari, Rino S. Seedor, Eric Bernicker, Sarah A. Weiss, Gregory A. Daniels, Timothy J. Panella, Hannah Frances Ryan, Howard Goodall, and Ryan J. Sullivan. DOI: 10.1200/JCO.2023.41.16_suppl.TPS9594 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) TPS9594-TPS9594.
