Phase 2 KEYNOTE-695 Trial for Melanoma Treatment Did Not Reach Primary Endpoint
Source: Dermatology Times, March 2023
The phase 2 KEYNOTE-695 trial (NCT03132675), conducted by OncoSec Medical Incorporated, observed the efficacy of the combination of interleukin 12 (IL-12) encoding plasmid tavokinogene telseplasmid (TAVO-EP) plus IV pembrolizumab (Keytruda, Merck & Dohme LLC). Study participants had to be diagnosed with unresectable or metastatic melanoma, stage III/IV, who were progressing on either pembrolizumab or nivolumab (Opdivo). Patients in the trial had confirmed disease progression after at least 12 weeks exposure to immediate prior anti-PD-1 antibody therapy.
Researchers observed patients during a treatment period of up to 2 years. Eligible patients were treated with tavo-EP to lesions every 6 weeks on days 1, 5, and 8. Then, they were treated with IV pembrolizumab (200 mg) on day 1 of each 30week cycle. Patients underwent 18 TAVO-EP cycles and 35 pembrolizumab cycles from baseline in a span of 2 years or until disease progression. The trial’s last patient started treatment in December 2020 and the clinical database lock happened in October 2022. Overall response rate (ORR) per blinded independent central review (BICR) served as the trial’s primary end point. Secondary end points included investigator-assessed ORR, DOR, progression-free survival (PFS), immune PFS, immune ORR, and overall survival (OS).
“Among 98 efficacy evaluable patients with at least one post-baseline tumor assessment, the confirmedORR per response evaluation criteria in solid tumors (RECIST) v1.1 by BICR assessment is 10.2% (95% confidence interval: 5.00, 17.97), which did not achieve the pre-specified clinically meaningful ORR of ?17% (95% CI: 10.2, 25.8),” study researchers noted. “The BICR review results for 98 efficacy evaluable patients are lower than the ORR per RECIST v1.1 by investigator assessment of 18.8% for the 101 patients previously reported as the key secondary endpoint of the KEYNOTE-695 trial."