T-VEC Plus Pembrolizumab Combo Shows Activity in Advanced Melanoma

The combination of the attenuated oncolytic virus talimogene laherparepvec (T-VEC) and the immune checkpoint inhibitor pembrolizumab shows activity and is well tolerated by advanced melanoma patients, according to a new study presented at the Society for Melanoma Research 2015 International Congress, held November 18–21 in San Francisco.

T-VEC, recently approved for the treatment of advanced melanoma, is an oncolytic herpes simplex virus type 1 engineered to replicate selectively in tumor cells and express human granulocyte-macrophage colony-stimulating factor.

A recent study showed that T-VEC in combination with ipilimumab resulted in an overall response rate of 50%, durable response rate of 44%, and tolerable safety profile in patients with advanced melanoma, said Georgina Long, BSc, PhD, MBBS, of the Melanoma Institute Australia in Sydney.

She reported on the primary analysis of MASTERKEY-265, a phase Ib study of T-VEC and pembrolizumab for treatment-naive patients with unresected stage IIIB/IV melanoma. Five weeks prior to initiating pembrolizumab, patients were given intralesional T-VEC injection at doses up to 4 mL per treatment (106 PFU/mL, then 108 PFU/mL every 2 weeks). Pembrolizumab 200 mg was then administered intravenously every 2 weeks.

Treatment continued until disease progression, development of intolerance, injectable tumor disappearance (T-VEC only), or 2 years.

Most of the 21 patients, median age 58, had good performance status; 19% of the patients had BRAF-positive melanoma. All of the patients received one or more doses of T-VEC and pembrolizumab. Median treatment duration was 15 weeks and 8 infusions for T-VEC and 12 weeks and 6 infusions for pembrolizumab.

Of the 16 evaluable patients, 9 achieved an objective response (56.3%) and the disease control rate was 68.8%. “We saw responses in every stage of disease,” Dr. Long said.

Changes in tumor burden over the course of treatment were typical of the response kinetics seen with T-VEC, she noted.  

All of the patients experienced adverse events. The most common ones were fatigue (11 patients), pyrexia (10 patients), chills (9 patients), fatigue (8 patients), and headache and nausea (7 patients each). One-third of the patients had grade 3 adverse events, including five patients each with headache or diarrhea.

Adverse events led to three interruptions in T-VEC treatment and five interruptions in pembrolizumab treatment.

All patients had treatment-related serious adverse events and 24% had grade 3 treatment-related adverse events. There were no dose-limiting toxicities (DLTs) and no grade 4 treatment-related adverse events.

In conclusion, Dr. Long said: “T-VEC plus pembrolizumab was well tolerated, with no DLTs. Treatment-related adverse events were mostly grade 1 or 2. No patients discontinued due to treatment-related adverse events.”

The preliminary response data are promising, she said. An updated analysis of phase Ib safety and efficacy is planned.

A double-blind, placebo-controlled phase III study has been designed to include 660 patients with treatment-naive, stage III/IV melanoma with injectable lesions. The study will include 330 patients receiving T-VEC plus pembrolizumab and 330 patients taking placebo injections plus pembrolizumab. The primary endpoints, progression-free survival and overall survival, “will allow us to truly see the value of the T-VEC/pembrolizumab combination,” Dr. Long said.