KEYNOTE-629

Background

Phase 2, open-label, nonrandomized, multicenter KEYNOTE-629. N=159 cutaneous squamous cell carcinoma (cSCC) in two cohorts: recurrent/metastatic (R/M; n=105) and locally advanced unresectable (laCSCC; n=54). Pembrolizumab (anti-PD-1); no prior systemic therapy for advanced disease; no PD-L1 selection. ECOG PS 0–1; 59 global centers.

Interventions and follow up

Treatment: Pembrolizumab 200 mg IV q3w for up to 35 cycles (~2 years) (single-arm)
Primary endpoint: ORR per RECIST 1.1 by independent central review
mFollow up: 11.0 months (R/M cohort)

Results

ORR (R/M cSCC): 34.3% (36/105; 95% CI 25.4–44.0)
ORR (laCSCC): 35.2% (19/54; 95% CI 22.7–49.4)
mPFS (R/M): 5.7 months (95% CI 3.1–8.5)
mOS (R/M): 23.8 months (95% CI 13.4–29.8); 12-mo OS 61.0%, 24-mo OS 48.4%

Adverse events

Grade ≥3 TRAE: 13.8% (R/M cohort)
Most common grade ≥3: increased ALT 3.8%, fatigue 1.9%, increased AST 1.9%
Immune-mediated: hypothyroidism, pneumonitis, colitis
Discontinuation due to AEs: 7.6%

Conclusions

Pembrolizumab achieved 34% ORR with mOS 23.8 months in recurrent/metastatic cSCC and a favorable toxicity profile. Provided the confirmatory single-arm dataset supporting FDA approval of pembrolizumab for advanced CSCC, an alternative to cemiplimab.

Key Limitations

Single-arm, nonrandomized; no head-to-head vs cemiplimab. ORR surrogate primary endpoint; short median follow-up (11 mo). Cross-trial efficacy comparisons unreliable.

Clinical Context

Pembrolizumab FDA-approved (2020) for recurrent/metastatic and locally advanced CSCC; an ESMO-recognized anti-PD-1 alternative to cemiplimab as first-line systemic therapy for advanced disease.

References