CheckMate 358 (MCC)

Background

Phase 1/2, open-label, multicenter CheckMate 358 (virus-associated tumor cohort, neoadjuvant). N=39 resectable Merkel cell carcinoma (MCC), no prior systemic therapy for resectable disease. Anti-PD-1 given before surgical resection. Tumor MCPyV status and PD-L1 expression correlated with outcomes.

Interventions and follow up

Treatment: Nivolumab 240 mg IV on day 1 and day 15 (two doses) before surgery — neoadjuvant (single-arm)
Primary endpoint: Pathologic complete response rate (pCR) in resected specimen
mFollow up: 20.3 months (median, for 36 patients who underwent surgery)

Results

pCR rate: 47.2% (17/36 who underwent surgery)
Radiographic ORR (pre-surgery): 47% (17/36)
Pathologic partial response: 17% (6/36)
RFS at 12 mo (pCR vs no pCR): 100% vs 53.7%

Adverse events

Any-grade immune-related AEs: 36% (14/39)
Grade ≥3 TRAE: 10%
Immune-mediated: hyperthyroidism 13%, rash 8%, hypothyroidism 8%
Surgery delays from immune AEs: None
Treatment-related deaths: None

Conclusions

Neoadjuvant nivolumab followed by surgery achieved a 47% pCR rate in resectable MCC — a remarkably high pathologic response. pCR strongly predicted improved relapse-free survival (RFS 100% at 12 mo in pCR group). Supports neoadjuvant immunotherapy in resectable MCC and established the pCR-to-RFS correlation.

Key Limitations

Single-arm, nonrandomized; small N (39). pCR is a surrogate endpoint; no randomized comparison vs surgery alone. 3 patients did not undergo surgery. Rare disease limits generalizability.

Clinical Context

Neoadjuvant anti-PD-1 in MCC remains investigational; not yet a standard ASCO/ESMO recommendation but increasingly explored. Standard of care for resectable MCC remains surgery with or without adjuvant radiation.

References