Intratumoral therapy

PENNINGTON, NJ & SAN DIEGO—OncoSec Medical Incorporated, a late-stage biotechnology company developing immunotherapy cancer treatments using a plasmid DNA delivery platform, announced encouraging data for patients with aggressive metastatic melanoma who have no effective treatment options after they fail to respond to the standard of care—checkpoint inhibitor therapy—alone. At an investor conference in late 2020, OncoSec described its treatment regimen as a multibillion-dollar market opportunity.

OncoSec’s positive interim data were from its KEYNOTE-695 registration-enabled Phase 2b clinical trial evaluating TAVO (tavokinogene telseplasmid), a DNA plasmid-based interleukin-12 (IL-12), in combination with Keytruda (pembrolizumab) in rigorously defined anti-PD1 checkpoint-resistant metastatic melanoma patients. The results demonstrated a 30-percent (16/54) overall response rate in the first 54 of 100 planned patients. The complete response rate was 6 percent (3/54), and responses were durable up to 2 years.

OncoSec’s gene therapy technology combines TAVO with an intratumoral electroporation gene delivery platform. This is designed to achieve endogenous IL-12 production in the tumor microenvironment that allows the immune system to target and attack tumors throughout the body. TAVO has demonstrated a local and systemic antitumor response in several clinical trials, including the pivotal Phase 2b trial KEYNOTE-695 for metastatic melanoma and the KEYNOTE-895 Phase 2 trial in triple-negative breast cancer (TNBC). TAVO has received Orphan Drug and Fast-Track designations by the FDA for the treatment of metastatic melanoma following progression on Keytruda or Opdivo.

Using electroporation, an electric current that triggers the uptake and production of IL-12 locally, TAVO is administered directly into the tumor site in only a few minutes. This enables the immune system to target and attack both local and metastatic tumors throughout the body while avoiding toxic side effects. The differentiated platform delivers a proprietary therapeutic that enables a patient’s own tumor cells to express IL-12 and become responsive to checkpoint inhibitors.

“The TAVO-electroporation (TAVO-EP) delivery system works by optimizing cellular uptake of DNA-based IL-12 in the tumor microenvironment, leading to local, sustained production of IL-12 in the tumor, where it matters, with negligible systemic exposure,” according to Dr. Adil Daud of the University of California, San Francisco, who is professor of medicine, the director of melanoma clinical research, and lead author of the study. “This methodology captures and primes immune cancer-fighting cells in the tumor, leading to systemic immune responses without systemic toxicity. The totality of the safety and efficacy data establishes TAVO-EP as a best-in-class intratumoral therapy.”

“Achieving an overall response rate of 30 percent with several complete responses and no serious adverse events is extremely encouraging for checkpoint-resistant metastatic melanoma patients who currently rely on systemic administration of immune-stimulating drugs associated with severe toxicity,” said Dr. Paolo A. Ascierto, director of the Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy at the National Tumor Institute Fondazione G. Pascale in Naples, Italy. “The data reported, in addition to its ease of use, demonstrate the potential of TAVO in combination with pembrolizumab as a next-generation intratumoral IL-12 therapy that can induce regression of both locally treated and untreated distant and visceral lesions.”

As Daniel O’Connor, CEO of OncoSec, explained, “Patients with recurrent metastatic melanoma are in great need of effective treatment options. We believe this data demonstrates not only strong levels of efficacy, but also very low treatment-related adverse events with the TAVO + pembrolizumab combo. This, combined with its ease of administration to accessible lesions within minutes in an outpatient setting, plus TAVO’s low-cost, simple manufacturing process and its off-the-shelf availability, build a strong case that the TAVO + pembrolizumab combination, in a real-world setting, could equip clinicians with more options for their patients.”

Approximately 100,000 American adults per year are diagnosed with metastatic melanoma—stage IV melanoma that has typically spread through the lymph nodes to distant sites in the body such as the liver, lungs, bones, and brain. Because of this metastatic tumor burden, stage IV melanoma can be very difficult to treat. Available treatment options often combine surgery with immunotherapy or targeted therapy, but the five-year survival rate for metastatic melanoma patients is only about 25 percent.