ESMO Congress 2026

The class evidence for neoadjuvant immunotherapy is already firm. In the phase 3 NADINA trial, 423 patients with resectable, macroscopic stage III melanoma were randomized to two cycles of neoadjuvant ipilimumab plus nivolumab followed by surgery, or surgery followed by 12 cycles of adjuvant nivolumab, with only partial or nonresponders in the neoadjuvant group continuing to adjuvant therapy; at a median follow-up of 9.9 months, 12-month event-free survival was 83.7% versus 57.2%, with a difference in restricted mean survival time of 8.00 months ^[1]. The earlier randomized phase 2 S1801 interim analysis (median follow-up 14 months) had already shown a 23% EFS benefit, and the pathological rationale was established — single-agent anti-PD-1 achieving 20-30% MPR, doubled to 50-60% with ipilimumab plus nivolumab ^[3] — with commentary previously framing this shift as neoadjuvant therapy moving from a tool to reduce surgical morbidity toward treatment with curative promise ^[2]. Based on NADINA, neoadjuvant ipilimumab plus nivolumab has become standard therapy for stage III melanoma ^[6], and Morpheus-Melanoma likewise cited NADINA and SWOG-1801 as evidence that neoadjuvant outperforms adjuvant checkpoint inhibition ^[5].

At #ESMO26, the live posts did not report a single concrete readout but rather several parallel threads. @DrBetofMDPhD, opening the INMC meeting, said the field “has defined that neoadjuvant is superior to adjuvant IO,” with next steps being risk thresholds for <pCR, biomarkers and new combinations. @yakov_pakhomov focused on the control arm: for macroscopic stage III, neoadjuvant IO is now the bar (NADINA/S1801), but resected IIB/C and microscopic stage III have no neoadjuvant option — that is where INTerpath-001 matters, and “OS and subgroups will decide.” @JacobPlieth separately noted that sell-side analysts were firefighting $MRNA and endorsed the measured take from Evercore ISI's Cory Kasimov. The posts disclosed no specific efficacy numbers from this meeting.

Relative to existing knowledge, the discussion moves the agenda from “whether neoadjuvant is better” to “what to do next for patients without pCR.” In NADINA, neoadjuvant-group patients with a major pathological response had a 12-month recurrence-free survival of 95.1% ^[1]; PRADO's 5-year follow-up reported 71% event-free survival, 74% relapse-free survival, 79% distant metastasis-free survival and 86% overall survival, with high TMB, high IFNγ signature and PD-L1 expression of 1% or higher associated with favorable outcomes, and triple-high patients reaching 100% MPR and 100% 5-year event-free survival ^[6] — precisely the biomarker and risk-threshold direction the posts describe. “New combinations” also have a precedent: in Morpheus-Melanoma, tobemstomig showed a pathological response rate of 80.0% (32/40), not lower than nivolumab plus ipilimumab's 77.3% (17/22), though MPR was 62.5% versus 72.7% ^[5]. As for the IIB/C and microscopic stage III populations lacking a neoadjuvant option, the materials disclose no INTerpath-001 data; only the promised OS and subgroup analyses can answer.

The limitations are clear: the live posts are commentary with no new numbers, and the readout behind $MRNA is undisclosed; the citable long-term survival data come from the single-arm phase 2 PRADO of 99 patients ^[6]; NADINA's median follow-up was only 9.9 months ^[1]; and Morpheus-Melanoma is phase 1b/2 with limited arm sizes ^[5]. Cross-trial comparisons warrant caution, and whether EFS benefit translates into overall survival benefit remains to be confirmed.