Oncology

Single oral FMT added to first-line ICIs yields high ORR in advanced NSCLC and melanoma

In FMT-LUMINate, 40 untreated patients with advanced NSCLC or melanoma received a single healthy-donor oral FMT before standard first-line ICIs. NSCLC patients received FMT plus anti–PD-1, and melanoma patients received FMT plus combined anti–PD-1/anti–CTLA-4 therapy. ORR was 80% in NSCLC and 75% in melanoma, exceeding typical first-line benchmarks for these regimens. FMT was considered safe, with no grade ≥3 AEs in NSCLC and grade ≥3 AEs in 65% of melanoma patients, consistent with dual-ICI toxicity. Responders developed a distinct post-FMT microbiome with loss of specific bacterial species, which appeared necessary for FMT-mediated antitumor benefit. 1

Donor FMT trends toward improved outcomes with pembrolizumab–axitinib in first-line mRCC

TACITO randomized 45 treatment-naive mRCC patients to donor FMT or placebo FMT added to pembrolizumab plus axitinib. The 12-month PFS endpoint was not met, though disease-free at 12 months was numerically higher with donor FMT (70% vs 41%; P=0.053). Median PFS favored donor FMT at 24.0 vs 9.0 months (HR 0.50; P=0.035), with higher ORR (52% vs 32%). Safety was acceptable, with microbiome analyses confirming donor strain engraftment and greater diversity shifts in the donor-FMT arm. Specific strain acquisition or loss, rather than overall engraftment magnitude, correlated with clinical benefit. 2

Five-year PRADO data confirm durable benefit of neoadjuvant ipilimumab–nivolumab in stage III melanoma

In the PRADO phase 2 cohort of OpACIN-neo, 99 patients with stage III macroscopic melanoma received neoadjuvant ipilimumab plus nivolumab. At 5 years, event-free, relapse-free, distant metastasis-free, and overall survival were 71%, 74%, 79%, and 86%, respectively. Ongoing grade 1–2 immune-related AEs persisted in 69% of survivors, mainly vitiligo and hypothyroidism. Major pathologic response and high TMB, IFN-γ signature, and PD-L1 ≥1% were each associated with favorable long-term outcomes. Patients with combined high TMB, IFN-γ, and PD-L1 had 100% MPR and 100% 5-year event-free survival, versus 41% with triple-low expression. 3

Perioperative chemoimmunotherapy improves pCR, EFS, and OS in resectable gastric/GEJ cancer

This meta-analysis pooled seven randomized trials (2510 patients) comparing perioperative chemoimmunotherapy versus chemotherapy alone in resectable gastric/GEJ adenocarcinoma. Chemoimmunotherapy increased pCR from 6.1% to 17.6% (risk difference 0.11; 95% CI 0.09–0.14). Event-free survival improved (HR 0.76; 95% CI 0.66–0.86) and overall survival improved (HR 0.82; 95% CI 0.71–0.94). Benefits were statistically significant in PD-L1–positive tumors, with no clear advantage in PD-L1–negative disease. Grade ≥3 treatment-related AEs were similar between arms (66.1% vs 62.7%; risk difference 0.04; P=0.08), suggesting no major added toxicity. 4