JAVELIN Merkel 200

Background

JAVELIN Merkel 200 was a phase II, multicenter, single-group, open-label study (n=88) of avelumab in stage IV Merkel cell carcinoma that had progressed after ≥1 prior cytotoxic chemotherapy regimen. MCC is a rare aggressive neuroendocrine skin cancer with poor metastatic prognosis.

Interventions and follow up

Regimen: Avelumab (anti-PD-L1) 10 mg/kg IV q2w until disease progression or unacceptable toxicity.
Primary endpoint: Confirmed ORR (CR + PR) by independent review per RECIST 1.1.
mFollow up: 10.4 months (IQR 8.6–13.1)

Results

ORR: 31.8% (28/88; 95.9% CI 21.9–43.1), including 8 CR and 20 PR
Duration of response: Ongoing in 82% (23/28) of responders at analysis
Stable disease ≥6 weeks: Additional 28.4% of patients

Adverse events

Grade ≥3 TRAEs in 5 patients (6%): lymphopenia ×2, CPK increase, AST/ALT increase, cholesterol increase. No grade 4 TRAEs; no treatment-related deaths. Serious TRAEs in 5 patients (6%): enterocolitis, infusion-related reaction, hepatitis, chondrocalcinosis, synovitis, interstitial nephritis (each n=1).

Conclusions

Avelumab achieved a 31.8% ORR with durable responses (82% ongoing) in chemotherapy-refractory metastatic MCC with a favorable safety profile, establishing anti-PD-L1 blockade as the new standard for second-line advanced MCC.

Key Limitations

Single-arm design without randomized comparator; short median follow-up at data cutoff; no PD-L1 or MCPyV biomarker selection; enrolled exclusively chemotherapy-refractory patients.

Clinical Context

Avelumab (Bavencio) received FDA accelerated approval for metastatic MCC in March 2017 — the first FDA approval specifically for MCC. Pembrolizumab (KEYNOTE-017) was subsequently approved for first-line MCC. In first-line trials, anti-PD-1/PD-L1 agents achieve ~50–70% ORR, supplanting cytotoxic chemotherapy.

References