OncoSec Medical Incorporated, a company developing DNA-based intratumoral cancer immunotherapies, has reported new positive clinical data from a phase II investigator sponsored trial assessing the combination of OncoSec's investigational intratumoral therapy, ImmunoPulse IL-12, and the approved anti-PD- 1 therapy (pembrolizumab), in patients with unresectable metastatic melanoma. The results of this single-arm, open-label trial, which was led by the University of California, San Francisco (UCSF), indicated that ImmunoPulse IL-12 can increase response rates in patients who are not expected to respond to anti-PD-1 therapy alone.

The trial is evaluating the following key endpoints: best overall response rate (BORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune-related Response Criteria; safety and tolerability; duration of response; 24-week landmark progression-free survival (PFS); median PFS; and overall survival (OS). The study results showed an overall response rate (ORR) at 24 weeks of 43% (9/21), and BORR of 48% by RECIST v1.1. There were 24% (5/21) complete responders (CR), 19% (4/22) partial responders (PR), and 9% (2/21) stable disease (SD) for a total disease control rate of 52% (11/21). These data are consistent with, and expand upon, previously reported preclinical and clinical data that provide a strong rationale for combining ImmunoPulse IL-12 with anti-PD-1 blockade.

"Collectively, these data suggest that intratumoral IL-12 DNA with electroporation in combination with pembrolizumab can effectively alter the tumor microenvironment by triggering adaptive resistance," said Alain Algazi, M.D., the study's lead investigator, and skin cancer specialist in the Melanoma Center at the UCSF Helen Diller Family Comprehensive Cancer Center. "This increases the substrate for a therapeutic PD-1/PD-L1 blockade while driving systemic anti-tumor immunity and concordant clinical responses in patients unlikely to benefit from anti-PD-1 monotherapy."

Dr Algazi presented the study findings today in an oral presentation titled, "Immune monitoring outcomes of patients with stage III/IV melanoma treated with a combination of pembrolizumab and intratumoral plasmid interleukin 12 (pIL-12)" (Abstract #78), at the ASCO-SITC Clinical Immuno-Oncology Symposium in Orlando, FL.

In this trial, a biomarker that has previously been shown to be predictive of response to checkpoint inhibitor therapy was used to enroll 22 patients who have a low likelihood of responding to an anti-PD-1 therapy. These patients were treated with the combination of intravenous pembrolizumab and ImmunoPulse IL-12 for more than 24 weeks.

The combination therapy continued to demonstrate a favorable safety profile and was well tolerated. Importantly, of the 22 patients enrolled, nine had previous checkpoint inhibitor therapy; ORR for this subset of patients was 33% (3/9).

Comprehensive immune monitoring of blood and tissue samples showed that the combination  of ImmunoPulse IL-12 with pembrolizumab produces a safe and powerful systemic immune response. This response leads to an increase in tumor-specific CD8+ T-cells and an "adaptive immune resistance" that broadly supports an immune-directed mechanism that is differentiated between responders and non-responders. Analysis of the biomarker data suggests that the combination of ImmunoPulse IL-12 with pembrolizumab is transforming "cold" tumors, which would be predicted to not respond to anti-PD-1 therapy, into "hot" tumors, thus increasing the potential for a meaningful clinical response to the checkpoint inhibitor therapy. Moreover, an analysis of pre-treatment samples using various analytical methods that have also been demonstrated to predict response to anti-PD-1 therapy, including immunohistochemistry (IHC) and RNA expression of critical immune-related genes by NanoString, correlate with the predictive biomarker used to enroll patients for this study.

"OncoSec's vision to bring intratumoral gene therapies to the oncology market continues to advance with these positive, impactful data, which hold immense promise for cancer patients who are unlikely to benefit from immunotherapy," said Punit Dhillon, OncoSec president and chief executive officer. "These results provide a strong foundation for our planned phase II registration trial, which will evaluate the combination of ImmunoPulse IL-12 and an anti-PD-1 therapy in melanoma patients who have previously failed an approved anti-PD-1 therapy alone. We expect to initiate this study later in 2017."