Primary analysis of MASTERKEY-265 phase 1b study of talimogene laherparepvec (T-VEC) and pembrolizumab (pembro) for unresectable stage IIIB-IV melanoma
Year: 2016
Type: conference-paper
Study design: Clinical Trial
Abstract: Background: T-VEC is a herpes simplex virus-1 -based oncolytic immunotherapy designed to selectively replicate in tumors, pro- duce GM-CSF, and stimulate antitumor immune responses. T-VEC significantly improved durable response rate (DRR; primary end- point) in the T-VEC arm vs GM-CSF in OPTiM (Andtbacka et al. JCO 2015) and is approved in the US for local treatment of unresect- able cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. Pembro is a PD-1 block- ing antibody approved for the treatment of advanced metastatic or unresectable melanoma and has demonstrated superiority over the CTLA-4-blocking antibody ipilimumab in patients with stage III or IV melanoma (Robert et al. NEJM 2015). Both drugs have toler- able and non-overlapping adverse event (AE) profiles, and combin- ing them may enhance antitumor efficacy. Safety and preliminary efficacy data from the phase 1b primary analysis of a phase 1b/3 study of T-VEC + pembro in unresectable stage IIIB-IV melanoma (NCT02263508) are reported. Materials and methods: The primary endpoint is incidence of dose- limiting toxicities (DLT). Key secondary endpoints are objective response, survival, and AEs. Patients had stage IIIB-IV melanoma with injectable lesions, no prior systemic therapy, and ECOG PS 0-1. T-VEC was given ≤4 mL injected into (sub)cutaneous/nodal lesions 106 PFU/ mL d1, 108 PFU/mL d22 then Q2W. Pembro was given IV 200 mg d36 then Q2W. Treatment (tx) continues until. CR, all injectable tumors have disappeared (for T-VEC), confirmed PD per modified immune-related response criteria, intolerance of study treatment, 24 months from the date of the first dose of pembro or end of study, whichever occurs first. Results: 21 patients were enrolled Dec 2014-Mar 2015 with data cut- off of Jun 2015. Patient characteristics: median age 58 year; 48 % stage IIIB-IVM1a, 52 % stage IVM1b/c melanoma; 81 % PD-L1+; 76 % HSV+. Median follow-up time was 18.7 w. No DLTs were reported. All 21 patients had an AE: 29 % G3, no G4, and one G5 (not attributed to tx). Most common AEs were fatigue 52 %, pyrexia 48 %, chills 43 %, and rash 38 %. Of 16 patients ≥12 w after first pembro tx and with evalu- able response assessment, unconfirmed response rate per investigator was 56 %; disease control rate was 69 % (12.5 % CR, 44 % PR, 12.5 % SD, 31 % PD). Conclusions: T-VEC+ pembro can be given at full doses with no unexpected safety signals. Responses were seen in over half of eval- uable patients in this early efficacy analysis. A randomized phase 3 trial comparing T-VEC+ pembro vs T-VEC placebo + pembro is planned.
Authors: Dummer, Reinhard, Long, Georgina V., Ribas, Antoni, Puzanov, Igor, Michielin, Olivier, VanderWalde, Ari, Andtbacka, Robert H.I., Cebon, Jonathan, Fernandez, Eugenio, Malvehy, Josep, Olszanski, Anthony J., Gajewski, Thomas F., Kirkwood, John M., Gause, Christine, Chen, Lisa, Kaufman, David R., Chou, Jeffrey, Hodi, F. Stephen
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7130637220