Combining T-VEC and pembrolizumab does not significantly improve survival in advanced, unresectable melanoma

First and second interim analyses of the MASTERKEY-265 trial showed no significant benefit for the combination of T-VEC and pembrolizumab over pembrolizumab alone in patients with unresectable stage IIIB/IVM1c melanoma.

Previous research showed that oncolytic virotherapy with talimogene laherparepvec (T-VEC) may improve the efficacy of anti-PD-1 therapy in patients with advanced melanoma by changing the tumour microenvironment [1]. In the phase 3 MASTERKEY-265 trial (NCT02263508), 692 patients with unresectable stage IIIB-IVM1c, anti-PD-1-naïve melanoma with injectable lesions were randomised 1:1 to T-VEC/pembrolizumab or placebo/pembrolizumab. T-VEC was given at ≤4x10⁶ plaque-forming units (PFU) followed by ≤4x10⁸ PFU 3 weeks later and every 2 weeks until dose 5, and every 3 weeks thereafter. Pembrolizumab was given intravenously 200 mg every 3 weeks. Dual primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), complete response rate (CRR), durable response rate (DRR), duration of response (DOR), and safety. Dr Helen Gogas (National and Kapodistrian University of Athens, Greece) presented the first results of MASTERKEY-265 [2].

The primary endpoints did not reach statistical significance. After a median follow-up of 31.0 months, median PFS was 14.3 months for the T-VEC/pembrolizumab-treated patients and 8.5 months for the placebo/pembrolizumab-treated patients (HR 0.86; P=0.13); 1-and 2-year PFS rates were 53.8% versus 45.7% and 41.9% versus 38.6%, respectively (see Figure).

Figure: PFS, primary endpoint of MASTERKEY-265 [2]



Median OS was not reached for the T-VEC/pembrolizumab arm and 49.2 months for the placebo/pembrolizumab (HR 0.96; P=0.74). OS was not expected to achieve statistical significance at the primary OS analysis. Safety profiles were generally comparable between treatment arms.

“Combining T-VEC and pembrolizumab does not significantly improve PFS or OS in patients with unresectable stage III/IVM1 melanoma,” concluded Dr Gogas.

1. Ribas A, et al. Cell. 2017;170:1109-1119.
2. Gogas HJ, et al. MASTERKEY-265: A phase III, randomized, placebo (Pbo)-controlled study of talimogene laherparepvec (T) plus pembrolizumab (P) for unresectable stage IIIB–IVM1c melanoma (MEL). Abstract 1037O, ESMO Congress 2021, 16–21 September.

 

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Posted on 19 November, 202115 February, 2024