Day 4 — Monday, June 1¶
After Sunday's Plenary fireworks, Monday was the day the disease-specific oral sessions delivered their own headliners. The standout was a rare-tumor win — OptimUM-02, the first phase 3 to establish a systemic standard in HLA-A02:01–negative metastatic uveal melanoma — but the day was defined as much by two instructive negatives in lung cancer (ANVIL/ALCHEMIST and TRIPLEX*) and a GI HER2 win that reshapes first-line gastroesophageal treatment.
Melanoma: a first standard for uveal melanoma¶
In the 9:00 a.m. Melanoma/Skin Cancers session, OptimUM-02 gave a population with no approved systemic options a genuine one. In 1L HLA-A02:01–negative metastatic uveal melanoma, darovasertib (PKC inhibitor) + crizotinib beat investigator's choice of therapy on median PFS — 6.9 vs 3.1 months (HR 0.42, 95% CI 0.30–0.59, p<0.0001)* — with ORR 37.1% vs 5.8% (p<0.0001) and an early OS trend favoring the combination. Grade 3/4 treatment-related events were manageable (diarrhea 10.0%, syncope 7.1%). The darovasertib NDA is already under FDA Real-Time Oncology Review.
Lung: two negatives that teach¶
Monday's lung program was dominated by trials that did not hit — but informatively so. ANVIL/ALCHEMIST (EA5142), the largest US cooperative-group trial of adjuvant immunotherapy in NSCLC (N=935, Abstract 8000), reported that adjuvant nivolumab after surgery and chemotherapy did not improve disease-free survival in resected EGFR/ALK–wild-type disease — median DFS 71.3 vs 68.8 months (HR 0.97, 95% CI 0.81–1.17, P=.39) — and missed even in the PD-L1≥50% subgroup (HR 0.86). The contrast with neoadjuvant CheckMate 816 sharpened the field's view that checkpoint blockade works best with an intact tumor present to prime T cells.
TRIPLEX (NCT05223647, NTNU/Grønberg), a phase 3 adding thoracic radiotherapy to 1L carboplatin/etoposide + durvalumab in extensive-stage SCLC, was terminated early on the recommendation of its Data Safety Committee for excess toxicity — a cautionary readout for layering concurrent radiation onto chemo-immunotherapy in ES-SCLC. Detailed efficacy figures remained embargoed at writing.
GI: zanidatamab resets 1L HER2+ gastroesophageal cancer¶
HERIZON-GEA-01 brought a practice-changing win to first-line HER2+ locally advanced/metastatic gastroesophageal adenocarcinoma. Zanidatamab + chemo ± tislelizumab beat trastuzumab + chemo on both endpoints — PFS HR 0.63 (median 12.4 vs 8.1 months, P<0.0001) and OS HR 0.72 (26.4 vs 19.2 months, P=0.0043). A companion analysis (Abstract 4010) showed the triplet's benefit held across PD-L1 status, with PD-L1–negative triplet median OS reaching 29.7 months — addressing the field's worry that anti–PD-1 benefit concentrates in PD-L1–high disease.
GU: an early signal in post-EV urothelial¶
In a first-in-human dose-escalation reported during the meeting, NEXUS-01 tested the Nectin-4 topoisomerase-I ADC LY4052031 in 36 patients with metastatic urothelial carcinoma after enfortumab vedotin: ORR 33% (47% at 3.6 mg/kg), DCR 75%, median DOR 7.4 months — though no responses followed a prior topo-I ADC, flagging a cross-resistance limit worth watching.
Bottom line: Monday's signal trial was OptimUM-02, which finally puts a standard under HLA-A*02:01–negative uveal melanoma. But the day's real teaching came from lung — adjuvant nivolumab's flat ANVIL curve and TRIPLEX's toxicity halt both narrowing where and how to deploy immunotherapy — while HERIZON-GEA-01 handed gastroesophageal cancer a new first-line backbone.
Sources: IDEAYA/Servier — OptimUM-02 at ASCO · CancerNetwork — adjuvant nivolumab ANVIL negative · ECOG-ACRIN — ASCO 2026 research guide · ClinicalTrials.gov — TRIPLEX (NCT05223647) · OncoDaily — ASCO 2026 lung preview