A combination of Tavo (tavokinogene telseplasmid/IL-12) and Keytruda (pembrolizumab) was effective at reducing tumors in advanced melanoma patients who had failed prior anti-PD-1 therapies, according to early results of a Phase 2b trial.
OncoSec Medical’s Tavo is intended to deliver the immune-stimulating protein interleukin-12 (IL-12) into the tumor microenvironment, inducing controlled and localized production of IL-12, and enabling the immune system to attack tumors throughout the body. Tavo was previously granted orphan drug and fast-track designations by the FDA.
The open-label, multicenter Phase 2b KEYNOTE-695 (PISCES) trial (NCT03132675) is assessing the combination of Tavo with intravenous (into the vein) Keytruda (by Merck, known as MSD outside the U.S. and Canada) in patients with refractory, locally advanced or metastatic disease, which progressed despite at least four prior cycles with either Keytruda or Bristol-Myers Squibb’s Opdivo (nivolumab). Patient enrollment is still ongoing, and more information is available here.
Both Keytruda and Opdivo are a type of therapy called an immune checkpoint inhibitor. They bind to a protein called PD-1 on immune T-cells to prevent their binding to PD-L1 on tumor cells, which use this binding to evade immune attack.
All participants must receive their first Tavo/Keytruda treatment within 24 weeks of the last dose of their anti-PD-1 therapy and no other treatments prior to enrollment in the trial. Patients eligible to receive BRAF inhibitors must have received and progressed following such treatment.
As of Sept. 1, 21 patients had been enrolled, nine of whom had completed 12 weeks of treatment and reached the first tumor evaluation point. Five of these nine patients had had more than one line of therapy.
All participants had a marked increase in the number of immune cells inside the tumor — previously associated with improved overall survival in metastatic melanoma — following treatment.
In addition, the combination shrank the tumors of two patients (22%) and one patient reached disease stabilization. Overall, the disease control rate was 33%.
Importantly, patients experienced improvements in both treated and untreated lesions. One of the two responding patients had also progressed after four cycles of Opdivo and Bristol-Myers Squibb’s Yervoy (ipilimumab).
Treatment-related increase of immune-based RNAs in the tumor microenvironment and of intratumoral T-cells were associated with tumor responses.
“The preliminary tumor responses (22% BORR and 33% DCR) and supporting immune data observed here for the first time are important,” Adil Daud, MD, a health sciences clinical professor in the Department of Medicine (Hematology/Oncology) at the University of California San Francisco, said in a press release. “A 10% response rate is considered meaningful in this cohort, since this is about what we expect with additional chemotherapy.
“Since patients in KEYNOTE-695 have unequivocally failed approved anti-PD-1 therapies, these preliminary data, viewed in this context, carry weight,” said Daud, who is also the director of Melanoma Clinical Research at the UCSF Helen Diller Family Comprehensive Cancer Center.
Tavo was well-tolerated, with mild adverse advents associated with injection site or procedural pain. One treatment-related severe adverse event of cellulitis — a bacterial skin infection — was resolved.
Preliminary results of the trial were recently presented at the 33rd Annual Meeting of the Society for Immunotherapy of Cancer in Washington, D.C.
In 2017, before starting the study, OncoSec reviewed the patient inclusion criteria with the U.S. Food and Drug Administration, so that KEYNOTE-695 could be submitted for accelerated approval. To be eligible for this program, a treatment candidate must address a serious condition and provide a relevant advantage over available alternatives.
The trial is expected to be completed in 2019. OncoSec expects to file for accelerated approval by the end of 2019 or in early 2020.
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