On April 23, 2019 OncoSec Medical Incorporated (OncoSec) (NASDAQ:ONCS), a company developing intratumoral cancer immunotherapies, reported a triple combination clinical trial of OncoSec’s TAVO, epacadostat, and KEYTRUDA in patients with squamous cell carcinoma head and neck (SCCHN) cancer (Press release, OncoSec Medical, APR 23, 2019, View Source [SID1234535327]). This study, the "TRIFECTA" study, will be conducted by the UCSF Helen Diller Family Comprehensive Cancer Center.
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TRIFECTA, formally entitled, "The Trifecta Study: Optimizing Antitumor Immunity Using Tavokinogene Telseplasmid with Electroporation, Pembrolizumab, and Epacadostat in Squamous Cell Carcinoma of the Head and Neck," will evaluate the combination use of OncoSec’s TAVO (intratumoral IL-12 tavokinogene telseplasmid), epacadostat (IDO inhibitor), and KEYTRUDA (pembrolizumab, an anti-PD1 monoclonal antibody) in patients with SCCHN cancer.
TRIFECTA will be an investigator-initiated clinical trial by UCSF otolaryngologist, Dr. Chase Heaton, to determine whether the triple combination can increase the overall response rate (ORR) in SCCHN compared with historical data for KEYTRUDA as a monotherapy. The costs of this clinical trial will be shared with others and will require minimal financial commitment from OncoSec.
The response rate in patients with unresectable SCCHN is very low when treated with anti-PD1 antibodies as a monotherapy, with only 13-16%1 2 durable remissions. Treatment failures are more common in patients whose tumors either lack anti-tumor immune cells or have an overabundance of regulatory immune cells that suppress effective anti-tumor immune responses. TAVO has previously demonstrated the ability to reverse this type of anti-PD-1 resistance in patients with metastatic melanoma.
"Effective anticancer immune responses require three steps, including immune priming and tumor infiltration with T cells; activation of partially exhausted TILs; and selective modulation of T cell populations to maximize the ratio of effector to regulatory immune cells," said Dr. Alain Algazi, Associate Professor of Clinical Medicine at UCSF and Clinical Strategic Advisor to OncoSec. "Based on this framework, we hypothesize that the combination of TAVO’s tumor infiltration mechanism, with pembrolizumab’s TIL technology and epacadostat’s T cell modulating capabilities will substantially increase the ORR to pembrolizumab in patients with SCCHN and that the combination will be well tolerated in this population."
TRIFECTA is a single-arm open-label clinical trial in which 35 evaluable patients will receive TAVO, pembrolizumab, and epacadostat. The primary endpoint of the study is overall response rate (ORR) by RECIST v1.1 and will be compared to historical data for pembrolizumab monotherapy in SCCHN and to existing data regarding the combination of pembrolizumab and epacadostat.
Melanoma patients in the anti-PD-1 refractory setting have found renewed clinical responses with the combination of KEYTRUDA with TAVO in the KEYNOTE-695 trial. TAVO’s mechanism of action may also enhance the activity of epacadostat as expression of IDO is driven by IFN-g, which, in TAVO-treated patients may create a broader target and therefore opportunity to limit this suppressive IDO axis. Due to its favorable safety profile, clinical activity and ability to trigger adaptive resistance (increases in both IDO and PD-L1 expression) via a robust IFN-g response, TAVO is a strong backbone for a combination strategy with epacadostat and Merck’s anti-PD-1 antibody, pembrolizumab.
"Supporting this investigator-initiated clinical is a very cost-effective way to learn if the three-way combination of TAVO, epacadostat and pembrolizumab can significantly improve the historical anti-PD-1 monotherapy durable remission response rate of 13-16%," said Daniel O’Connor, President and Chief Executive Officer of OncoSec. "Studies such as these continue to build on the body of clinical evidence in support of TAVO in a variety of combination therapies. We believe it is important to support investigator led studies such as this one, especially considering the prestige of the medical institution and the oncologists involved."