OncoSec Medical has presented positive interim clinical trial data showing that its ImmunoPulse IL-12 intratumoral therapy, in combination with Merck‘s Keytruda (pembrolizumab), improved clinical response in patients with unresectable metastatic melanoma who are unlikely to respond to PD-1 inhibitors alone.
The poster was presented today by Dr. Alain Algazi, the trial’s principal investigator, at the Society for Immunotherapy of Cancer (SITC) Annual Meeting, running through Nov. 13 in National Harbor, Maryland.
Results came from an ongoing, open-label, single-arm Phase 2 clinical trial (NCT02493361) led by the University of California, San Francisco (UCSF), evaluating if using OncoSec’s ImmunoPluse IL-12 in combination with Keytruda increases response rates in patients with advanced melanoma.
An article in the Journal of Clinical Investigation, published in August, reported that patients with low levels of a subset of CD8 T-cells have poor responses to monotherapy with PD-1 inhibitors like Keytruda, the company announced at the time. Based on those findings, OncoSec used the levels of those cells as a biomarker to identify patients with low likelihood of responding to PD-1 inhibitors alone and to enroll them in the trial.
A primary study endpoint was best overall response rate, measured by RECIST v1.1, and secondary endpoints included safety and tolerability, duration of response, 24-week landmark progression-free survival (PFS), median progression-free survival, and overall survival (OS).
Interim efficacy and safety data are available on 15 patients with metastatic melanoma not-responding to anti-PD1 (more than 40 are enrolled). Overall response rate was 40 percent, or six of the 15: four complete responses and two partial responses. The treatment was well-tolerated and had an acceptable safety profile.
Tumor biopsies and blood analysis showed that treatment efficacy correlated with an increase in the number of CD8+ T-cells inside the tumor, as well as modified RNA expression in the tumor and concordant immune cells in circulation, all markers of improved immune response. These results suggest that the combination treatment enables an effective anti-PD-1 response in non-responsive patients.
“Although this open-label study is still ongoing and data are maturing, I am encouraged by the meaningful interim response rates that the combination of ImmunoPulse IL-12 and pembrolizumab has been able to achieve in a patient population otherwise expected to respond poorly to pembrolizumab alone,” Algazi, an oncologist with the Melanoma Center at UCSF, said in a press release. “While checkpoint inhibition has conferred meaningful clinical benefit for advanced melanoma patients, there remains an urgent need to increase these agents’ efficacy through the rational combination with other immunotherapies.
“I look forward to the continued maturation of this data and to further reporting on the trial’s progress.”
ImmunoPulse therapy is designed to improve the delivery and uptake of DNA-based immune-targeting agents. ImmunoPluse IL-12, in particular, consists in the delivery to tumor cells of a DNA vector containing the IL-12 gene. Upon entry, tumor cells start producing and secreting the IL-12 protein, which attracts immune cells to the tumor environment.