Open-Label, Phase II Study of Talimogene Laherparepvec Plus Pembrolizumab for the Treatment of Advanced Melanoma That Progressed on Prior Anti–PD-1 Therapy: MASTERKEY-115
Mené sur 72 patients atteints d'un mélanome de stade avancé, cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement combinant talimogène laherparépvec (un virus oncolytique) et pembrolizumab après l'échec d'un traitement par anti-PD-1
Background: Treatment options for immunotherapy-refractory melanoma are an unmet need. MASTERKEY-115 phase II, open-label, multicenter trial evaluated talimogene laherparepvec (T-VEC) plus pembrolizumab in advanced melanoma that progressed on prior programmed cell death protein-1 (PD-1) inhibitors. Methods: Cohorts 1 and 2 comprised patients (unresectable/metastatic melanoma) who had primary or acquired resistance, respectively, and disease progression within 12 weeks of their last anti–PD-1 dose. Cohorts 3 and 4 comprised patients (resectable disease) who underwent complete surgery, received adjuvant anti–PD-1, and experienced recurrence. Cohort 3 were disease-free for < 6 months and Cohort 4 for ≥ 6 months after starting the adjuvant anti–PD-1 therapy and before confirmed recurrence. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included complete response rate (CRR), disease control rate (DCR) and progression-free survival (PFS) per RECIST v1.1 and irRC-RECIST, and safety. Results: Of 72 enrolled patients, 71 were treated. The ORR (95% CI) was 0%, 6.7% (0.2–32.0), 40.0% (16.3–67.7), and 46.7% (21.3–73.4) in cohorts 1–4, respectively; iORR was 3.8% (0.1–19.6), 6.7% (0.2–32.0), 53.3% (26.6–78.7), and 46.7% (21.3–73.4). iCRR was 0%, 0%, 13.3%, and 13.3%. Median iPFS (months) was 5.5, 8.2, not estimable [NE], and NE for cohorts 1–4, respectively; iDCR was 50.0%, 40.0%, 73.3%, and 86.7%. Treatment-related adverse events (TRAEs), grade ≥ 3 TRAEs, serious, and fatal AEs occurred in 54 (76.1%), 9 (12.7%), 24 (33.8%), and 10 (14.1%) patients, respectively. Conclusion: T-VEC-pembrolizumab demonstrated antitumor activity and tolerability in PD-1-refractory melanoma, specifically in patients with disease recurrence on or after adjuvant anti–PD-1.