In a 21-patient, phase 1b clinical trial evaluating the safety of the combination of intratumoral injections of oncolytic virus talimogene laherparepvec with i.v. administered anti-PD-1 (beginning on week 6) for the treatment of advanced melanoma, the generally well-tolerated therapy resulted in 62% confirmed objective response rate and 33% complete response rate, likely due to the virus-induced increase in CD8+ T cells, PD-L1 expression, and IFNγ expression within the tumor.
Here we report a phase 1b clinical trial testing the impact of oncolytic virotherapy with talimogene laherparepvec on cytotoxic T cell infiltration and therapeutic efficacy of the anti-PD-1 antibody pembrolizumab. Twenty-one patients with advanced melanoma were treated with talimogene laherparepvec followed by combination therapy with pembrolizumab. Therapy was generally well tolerated, with fatigue, fevers, and chills as the most common adverse events. No dose-limiting toxicities occurred. Confirmed objective response rate was 62%, with a complete response rate of 33% per immune-related response criteria. Patients who responded to combination therapy had increased CD8+ T cells, elevated PD-L1 protein expression, as well as IFN-gamma gene expression on several cell subsets in tumors after talimogene laherparepvec treatment. Response to combination therapy did not appear to be associated with baseline CD8+ T cell infiltration or baseline IFN-gamma signature. These findings suggest that oncolytic virotherapy may improve the efficacy of anti-PD-1 therapy by changing the tumor microenvironment. VIDEO ABSTRACT.
Author Info: (1) University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA. Electronic address: aribas@mednet.ucla.edu. (2) University Hospital of Zuric
Author Info: (1) University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA. Electronic address: aribas@mednet.ucla.edu. (2) University Hospital of Zurich, Zurich, Switzerland. (3) Roswell Park Cancer Institute, Buffalo, NY, USA. (4) The West Clinic, Memphis, TN, USA. (5) University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA. (6) Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. (7) Fox Chase Cancer Center, Philadelphia, PA, USA. (8) Hospital Clinic i Provincial de Barcelona, Barcelona, Spain. (9) Olivia Newton-John Cancer Research Institute, Austin Health, School of Cancer Medicine, LaTrobe University, Heidelberg, VIC, Australia. (10) Hopitaux Universitaires de Geneve, Geneva, Switzerland. (11) University of Pittsburgh Cancer Institute and Hillman UPMC Cancer Center, Pittsburgh, PA, USA. (12) The University of Chicago School of Medicine, Chicago, IL, USA. (13) Amgen Inc., Thousand Oaks, CA, USA. (14) Amgen Inc., South San Francisco, CA, USA. (15) Amgen Inc., Thousand Oaks, CA, USA. (16) Merck & Co., Inc., Kenilworth, NJ, USA. (17) Merck & Co., Inc., Kenilworth, NJ, USA. (18) Amgen Inc., Thousand Oaks, CA, USA. (19) Dana-Farber Cancer Institute, Boston, MA, USA. (20) Melanoma Institute Australia, The University of Sydney and Royal North Shore and Mater Hospitals, Sydney, NSW, Australia.
