On November 6, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ: ONCS), a company developing novel cancer immunotherapies based on its proprietary technology generating sustained intratumoral IL-12 levels, today reported preliminary data from KEYNOTE-695, a global, multicenter Phase 2b, open-label trial of intratumoral delivery of TAVO (tavokinogene telseplasmid / IL-12) with intravenous KEYTRUDA (pembrolizumab) in patients with unresectable, advanced melanoma (Press release, OncoSec Medical, NOV 6, 2018, View Source [SID1234530797]). Eligible patients had refractory, locally advanced or metastatic disease defined as unresectable Stage III/IV metastatic melanoma that had definitively progressed on a full-course of anti-PD-1 treatment with KEYTRUDA (pembrolizumab) or OPDIVO (nivolumab).
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As of September 1, 2018, 21 patients had been enrolled in the study. Out of the 21 patients, nine patients had completed 12 weeks of treatment and reached the first tumor evaluation point at approximately 12 weeks, while the remaining 12 patients had not yet reached the first tumor evaluation. All nine patients were previously treated and definitively progressed on anti-PD-1 therapies with 56% (5/9) having had more than one prior line of therapy. All enrolled patients had exceedingly low frequencies of intratumoral CD8+ peCTL (PD-1+/CTLA-4+) at screening with a notable increase in TIL density following treatment.
Two of the nine patients experienced a partial response and one patient had stable disease (22% BORR and 33% DCR) by RECIST v1.1. Tumor responses were noted in both treated and untreated lesions. Of the two responding patients, both had multiple prior rounds of anti-PD-1 therapy, with no response, and one had also progressed after 4
cycles of OPDIVO and YERVOY (ipilimumab), an FDA-approved anti-CTLA4 / anti-PD1 antibody combination. Tumor responses were associated with treatment-related upregulation of immune-based transcripts in the tumor microenvironment, as well as increased frequencies of intratumoral T cells within three weeks of therapy.
"There is currently no approved therapy for the KEYNOTE-695 patient population. A 10% response rate is considered meaningful in this cohort, since this is about what we expect with additional chemotherapy, however, such responses lack durability. The preliminary tumor responses (22% BORR and 33% DCR) and supporting immune data observed here for the first time are important," said Adil Daud, MD, HS Clinical Professor, Department of
Medicine (Hematology/Oncology), UCSF; Director, Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center.
KEYNOTE-695 enrollment criteria with respect to anti-PD-1 checkpoint failure is highly restrictive. In order to be considered an anti-PD-1 checkpoint failure, all patients must have Stage III/IV metastatic melanoma progressive disease after at least four prior cycles of either KEYTRUDA or OPDIVO. Disease progression is determined according to RECIST v1.1, measured by radiologic assessment, with confirmation of progression by second assessment. All patients must receive their first TAVO / KEYTRUDA combination treatment within 24 weeks of the last dose of an FDA approved anti-PD-1 therapy, with no intervening therapies between such failure and KEYNOTE695 enrollment. Patients that were BRAF eligible must have received and progressed
following BRAF treatment.
"Although several clinical studies have reported late-stage melanoma data in anti-PD-1 failures, such failures are inconsistently defined. This is a critical point," continued Dr. Daud. "Since patients in KEYNOTE-695 have unequivocally failed approved anti-PD-1 therapies, these preliminary data, viewed in this context, carry weight."
TAVO was well-tolerated, with Grade 1 adverse advents associated with injection site or procedural pain. One TAVO related Grade 3 SAE of cellulitis was reported and resolved.
KEYNOTE-695 is a registration-enabled clinical trial. In order to be eligible for accelerated approval, a product candidate must treat a serious condition and provide a meaningful advantage over available therapies. In early 2017 and prior to the commencement of the study, the Company reviewed the patient inclusion criteria with FDA so that KEYNOTE695 could be submitted to FDA for accelerated approval. KEYNOTE-695 is expected to
be completed in 2019. Based on the outcome of the study and feedback from FDA, the Company plans to file for accelerated approval by end of 2019 or early 2020.
TAVO has received both Orphan Drug and Fast-Track Designation by the U.S. Food & Drug Administration.