|The following article features coverage from the European Society for Medical Oncology (ESMO) Congress 2021. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
Combining talimogene laherparepvec (T-VEC) with pembrolizumab did not lead to a survival benefit for patients with advanced melanoma.
In the phase 1b part of MASTERKEY-265, T-VEC plus pembrolizumab showed promising complete response rate (CRR) of 33% in 21 patients with advanced melanoma. This led to the phase 3, randomized, double-blind MASTERKEY-265/KEYNOTE-034 study (ClinicalTrials.gov Identifier: NCT02263508) of T-VEC plus pembrolizumab vs placebo plus pembrolizumab in patients with unresectable stage III-IVM1c melanoma who were naive to anti-PD1 therapy.
Patients from 21 countries who had injectable lesions were randomly assigned to receive T-VEC plus pembrolizumab or placebo plus pembrolizumab. T-VEC was given at up to 4 x 106 PFU followed by up to 4 x 108 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) per modified RECIST by blinded independent central review and overall survival (OS).
Secondary endpoints included objective response rate (ORR), CRR, durable response rate (DRR), duration of response (DOR), and safety.
At the European Society for Medical Oncology (ESMO) Congress 2021, senior author Helen Gogas, MD, associate professor of medical oncology at the University of Athens in Greece, reported the primary PFS and interim OS analyses. A total of 692 patients, median age 64 years, were randomly assigned between the treatment arms; 346 patients received T-VEC plus pembrolizumab and 346 patients received placebo plus pembrolizumab.
At a median follow-up of 31 months, median PFS was 14.3 months for the T-VEC plus pembrolizumab arm and 8.5 months for the placebo plus pembrolizumab arm (hazard ratio [HR], 0.86). “This trial did not meet the PFS primary endpoint,” explained Dr Gogas.
Median OS was not reached for the T-VEC plus pembrolizumab arm and 49.2 months for the placebo plus pembrolizumab arm (HR, 0.96). “There difference in 1-year OS vs 2-year OS is minimal,” she said.
ORR was 48.6% for the T-VEC plus pembrolizumab arm (CRR 17.9%) and 41.3% for the placebo plus pembrolizumab arm (CRR, 11.6%). DRR was similar in both arms (42.2% in the T-VEC plus pembrolizumab arm and 34.1% for the placebo plus pembrolizumab arm). There was no difference in DOR between the 2 arms.
Safety profiles were generally comparable between treatment arms. No new safety concerns were identified, she said.
Grade 3 or higher treatment-emergent adverse events occurred in 161 (46.7%) patients receiving T-VEC plus pembrolizumab and 151 (44%) patients receiving placebo plus pembrolizumab. Grade 3 or higher treatment-related adverse events occurred in 73 (21.2%) patients receiving T-VEC plus pembrolizumab and 55 (16%) patients receiving placebo plus pembrolizumab.
“The combination of T-VEC plus pembrolizumab did not significantly improve PFS or OS, the two primary endpoints, over placebo plus pembrolizumab in advanced unresectable melanoma,” concluded Dr Gogas. “A 5.8 month statistically non-significant numeric difference in PFS was observed between the treatment arms. Safety results of T-VEC plus pembrolizumab were consistent with the known safety profiles of each agent alone.”
Disclosures: This research was supported by Amgen Inc. and Merck & Co. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Ribas A, Chesney J, Long GV, et al. MASTERKEY-265: A phase III, randomized, placebo-controlled study of talimogene laherparepvec plus pembrolizumab for unresectable stage III-IVM1c melanoma. Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract 1037O.