ASCO 2026 | Neoadjuvant ipilimumab, nivolumab, and relatlimab in resectable melanoma
Ahmad Tarhini, MD, PhD, Moffit Cancer Center, Tampa, FL, discusses findings from a Phase II trial (NCT06295159) evaluating neoadjuvant ipilimumab, nivolumab, and relatlimab triplet checkpoint inhibitor therapy targeting CTLA-4, PD-1, and LAG-3 in patients with resectable clinical stage IIIB–IIID melanoma. Results demonstrated encouraging antitumor activity, with a high major pathologic response rate, and a toxicity profile consistent with known data for this combination, warranting further investigation of this triplet regimen in this setting. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
Neo-INR was a single-arm neoadjuvant study of ipilimumab, nivolumab, relatlimab in patients with macroscopic resectable stages 3 and 4 M1A melanoma. This is a patient population with locally advanced disease that requires multidisciplinary treatment and there have been recent advances in the management of these patients with neoadjuvant therapy, but there is a continued need for us to improve efficacy by evaluating potent and novel combinations, which is what we try to do with this combination with INR...
Neo-INR was a single-arm neoadjuvant study of ipilimumab, nivolumab, relatlimab in patients with macroscopic resectable stages 3 and 4 M1A melanoma. This is a patient population with locally advanced disease that requires multidisciplinary treatment and there have been recent advances in the management of these patients with neoadjuvant therapy, but there is a continued need for us to improve efficacy by evaluating potent and novel combinations, which is what we try to do with this combination with INR. And the goal is to improve really the major pathologic responses, the event-free survival rates, and ultimately de-escalate surgery, de-escalate systemic therapy, and improve the treatment-free survival of these patients. The neoadjuvant phase of the study was relatively brief, meaning we gave only one cycle of ipilimumab and up to two cycles of nivolumab, relatlimab, concurrently, and then patients underwent surgery at about eight weeks, at which time we assessed the pathologic response rate and the primary outcome of major pathologic response. If patients had a major pathologic response or MPR, they went on to have observation. If they did not, then they received adjuvant therapy where the triplet was preferred in that setting. So the pathologic response outcomes resulted in a pCR, pathologic complete response rate of 63%, near pCR of about 10% or so, ending up in a major pathologic response rate, the primary outcome of 74 percent in this patient population. All of them went on to have observation, and none of these patients has recurred to date. Even among those where we did not see a major pathologic response and went on to have adjuvant therapy, again, we have not seen a recurrence event to date with a median follow-up of about 10.5 months or so at this time. So this is a promising, let’s say, approach. And again, going back to the premise of de-escalating systemic therapy and improving treatment-free survival, you know, going forward.
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