Dostarlimab/Cobolimab Combo for Melanoma Shows Promise & Tolerability
Meghan Mooradian, MD, discusses findings and implications of the phase 2 NEO-MEL-T study.
The primary analysis of the phase 2 NEO-MEL-T study (NCT04139902) evaluating the neoadjuvant therapy of dostarlimab (Jemperli) plus the anti-TIM-3 agent cobolimab in high-risk resectable melanoma was presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting as a late-breaking abstract. In an interview with Targeted OncologyTM, Meghan Mooradian, medical oncologist at Massachusetts General Hospital, discussed findings and implications from the study.
Primarily, the treatment was well tolerated, with no unusual safety signals observed in either arm. The majority of toxicities reported were grade 1 or grade 2. Approximately 12% of patients experienced a grade 3 toxicity, but notably, there were no grade 4 or grade 5 events, and no events that prevented or delayed surgery.
Importantly, 100% of patients in both the monotherapy and combination arms completed their 2 planned cycles of neoadjuvant therapy and therapeutic lymph node dissection.
The primary end point, major pathologic response (MPR), was reviewed per consensus criteria and centrally confirmed: In the monotherapy arm, the MPR rate was 33.3%, with all responses being pathologic complete responses (pCRs). In the combination arm, the MPR rate was 55.6%. Of these, 37% were pCRs, and 18.5% were near-complete responses.
This MPR rate of 55.6% in the combination arm significantly exceeded the historical control of 30%, with a P-value of 0.007.
Investigators also examined radiographic response, which, similar to other datasets, showed a discordance between responses seen on CT scans and those observed in pathologic samples. The overall radiographic response rate in the monotherapy arm was approximately 16%. In the combination arm, the radiographic response rate was about 33%. This discrepancy between radiographic and pathologic responses is something observed across various tumor types.
According to Mooradian, this study strongly suggests the additive benefit of TIM-3 inhibition in this context. The power of a randomized study like this lies in its ability to clearly show the contribution of individual components within a treatment regimen.
Moving forward, these findings validate the further exploration of TIM-3 in PD-1 naive settings, whether in a perioperative or metastatic disease context. Investigators are eager to see how it can contribute to improving patient outcomes.
Another key takeaway is the regimen's tolerability. This opens the door for considering TIM-3 not just in combinations, but potentially even in triplet strategies.
