On April 3, 2023 OncoSec Medical Incorporated (NASDAQ: ONCS) (the Company or OncoSec), a clinical-stage biotechnology company developing intratumoral immunotherapies to stimulate the patient’s immune system to target cancer cells and eradicate disease, reported primary endpoint data from the Phase 2 KEYNOTE-695 clinical trial (Press release, OncoSec Medical, APR 3, 2023, View Source [SID1234629754]). This global, open-label single-arm trial is evaluating TAVO-EP, OncoSec’s proprietary interleukin 12 (IL-12) encoding plasmid delivered by intratumoral electroporation, in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with unresectable or metastatic (Stage III/IV) melanoma who had confirmed disease progression after at least 12 weeks exposure to immediate prior anti-PD-1 antibody therapy (pembrolizumab or nivolumab). The last patient started treatment in December 2020; clinical database lock occurred in October 2022. The primary endpoint of overall response rate (ORR) per RECIST v1.1 assessed by blinded independent central review (BICR) was not met.
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Among 98 efficacy evaluable patients with at least one post-baseline tumor assessment, the confirmed ORR per 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). The BICR 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.
BICR assessment, i.e., review of the available images of treated and non-treated lesions by radiologists and oncologists, blinded to investigator assessments, showed that 4 patients had a complete response (CR), 6 patients had a partial response (PR), and 25 patients had stable disease (SD) as a best response, for a disease control rate (CR + PR + SD) of 35.7%. The durable response rate of ≥24 weeks is 8.2% and the median duration of response is 25.5 months (range: 6.83-not reached).
As previously reported, the median overall survival for all enrolled 105 patients was 22.7 months (95% CI: 14.4, 35.5), after a median follow-up period of 33.4 months. The combination therapy of TAVO-EP and pembrolizumab was generally well tolerated with Grade 3 treatment-related adverse events (TRAEs) in 4.8% of all enrolled patients. No patients in the KEYNOTE-695 trial or any other clinical trials evaluating TAVO-EP alone or in combination experienced Grade 4 or Grade 5 TRAEs.
The Company plans to pursue TAVO-EP in combination with anti-PD-1 therapy in the neoadjuvant melanoma setting
Advancing TAVO-EP in neoadjuvant melanoma is supported by data from an investigator-sponsored trial (IST) led by Dr. Ahmad Tarhini at H. Lee Moffit Cancer Center & Research Institute evaluating TAVO in combination with intravenous nivolumab (Neoadjuvant Immunotherapy With Tavo + Electroporation in Combination With Nivo. in Melanoma Patients – Full Text View – ClinicalTrials.gov). Interim data, presented in November 2022 as a poster (abstract #617) at the 37th Annual Meeting of the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), showed high clinical (70% ORR by RECIST v1.1) and pathological response rates (88.9% major pathological response, including 66.7% complete pathological response). Of note, several patients predicted to be non-responders to immune checkpoint blockade by biomarker analysis prior to treatment appear to respond to TAVO in combination with nivolumab, supporting further the mechanism of action of IL-12. A meeting with the FDA to discuss a phase 2 randomized trial design and future development plans in the melanoma neoadjuvant setting is scheduled in May 2023.
"Treatment of patients with anti-PD-1 refractory melanoma remains difficult with limited success for immune checkpoint inhibitor combinations and exploratory therapeutic approaches. It is disappointing that review by blinded central readers did not confirm the previously reported results by investigator assessment of the KEYNOTE-695 Phase 2 clinical trial in this patient population. However, we remain optimistic that the observed long duration of response and overall survival of 22.7 months in this heavily pre-treated patient population, together with previously reported preliminary results from Dr. Tarhini’s IST in the neoadjuvant melanoma setting, provide rationale for further development of TAVO-EP in combination with anti-PD-1 therapy. We plan to discuss these data and a draft protocol for TAVO-EP in combination with pembrolizumab for a randomized Phase 2 trial in the neoadjuvant setting at the upcoming meeting with the FDA to potentially initiate the trial in the second half of 2023," said Robert Arch, Ph.D., Chief Executive Officer of OncoSec. "I want to thank all patients who participated in the KEYNOTE-695 trial, the clinical teams who conducted this trial, and everybody at OncoSec who remain focused on developing TAVO-EP as a novel intratumoral treatment approach for cancer patients with unmet medical needs."