NEW YORK — Patients with advanced unresectable melanoma can safely receive combination therapy with full doses of talimogene laherparepvec and pembrolizumab, according to study results presented at HemOnc Today Melanoma and Cutaneous Malignancies.
In previous studies, talimogene laherparepvec (Imlygic, Amgen) — a herpes simplex virus-1-based oncolytic immunotherapy — significantly improved durable response rate in patients with advanced melanoma. Also, pembrolizumab (Keytruda, Merck) — an anti–PD-1 antibody — showed superiority over ipilimumab (Yervoy, Bristol Meyers Squibb) in patients with stage III or IV melanoma.
Georgina V. Long
Both drugs appeared tolerable and demonstrated nonoverlapping adverse event profiles.
In the MASTERKEY-265 study, Georgina V. Long, PhD, MBBS, FRACP, a clinical researcher from Melanoma Institute Australia, and colleagues evaluated the safety and efficacy of combination therapy with talimogene laherparepvec, often referred to as T-VEC, and pembrolizumab for treatment of unresectable stage IIIB to IV melanoma.
Patients received T-VEC injections of 4 mL or less into cutaneous, subcutaneous and nodal lesions, including 106 PFU/mL on day 1, and then 108 PFU/mL on day 22 and every 2 weeks thereafter. They also received 200 mg pembrolizumab injections on day 36 and then every 2 weeks thereafter.
Incidence of dose-limiting toxicities served as the primary endpoint. Researchers defined this as treatment-related grade 4 or worse adverse events or grade 3 or worse immune-related adverse events within the first 6 weeks of treatment.
The analysis included 21 patients (median age, 58 years) with stage IIIB-IVM1a melanoma (48%) or stage IVM1b/c melanoma (52%). The majority (76%) were herpes simplex virus-1–positive.
Median follow-up was 18.7 weeks.
Long and colleagues reported no dose-limiting toxicities; however, all patients experienced an adverse event, the most common of which were fatigue (52%), pyrexia (48%), chills (43%) and rash (38%).
Sixteen patients had evaluable response 12 weeks or more after their first pembrolizumab dose. In this group, investigators reported a 56% response rate (complete response, 12.5%; partial response, 44%) and a 69% disease control rate.
Researchers plan to conduct a randomized phase 3 trial to compare talimogene laherparepvec plus pembrolizumab with placebo plus pembrolizumab. – by Kristie L. Kahl
HemOnc Today was unable to confirm the researchers’ relevant financial disclosures at the time of reporting.
Reference: Long GV, et al. Primary analysis of MASTERKEY-265 phase 1b study of talimogene laherparepvec and pembrolizumab (pembro) for unresectable stage IIIB-IV melanoma. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; March 18-19, 2016; New York.