“The data reported, in addition to its ease of use, demonstrate the potential of [tavokinogene telseplasmid] 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,” said Paolo A. Ascierto, MD.
Tavokinogene telseplasmid (Tavo) in combination with pembrolizumab (Keytruda) in patients with rigorously defined anti-PD-1 checkpoint resistant metastatic melanoma led to a 30% overall response rate (ORR) in the first 54 patients enrolled, according to new positive interim data from the registration-enabled phase 2b KEYNOTE-695 clinical trial.
This interim investigator assessed ORR is much higher than the primary efficacy end point for the study, which is a 20% ORR determined by blinded independent review.
The study enrolled rapidly progressing patients with a median interval of 1.2 months between the last dose of anti-PD-1 and study treatment. However, the trial aims to enroll up to 100 patients with refractory, locally advanced or metastatic disease defined as unresectable stage III or IV metastatic melanoma that has definitively progressed on a full-course of anti-PD-1 treatment with pembrolizumab or nivolumab (Opdivo).
The complete response rate was 6% and all responses were confirmed by scans taken no earlier than after 6 months on the study. Moreover, the ORR was 35% in patients with stage IV M1c/M1d disease and 40% in patients with prior exposure to ipilimumab (Yervoy). In addition, 9% of patients had 100% reduction of target lesions.
The median duration of response is currently 12.2 months (95% CI, 5.6 to not evaluable) and the median study follow-up was 13.5 months.
Regarding safety, investigators observed a promising safety profile resulting from this intratumor treatment approach. Specifically, the study showed only 5.4% grade 3 treatment-related adverse events (AEs) and no grade 4 or 5 treatment-related AEs.
The data were selected for a poster discussion and will also be presented in the virtual poster hall at the Society for Immunotherapy of Cancer (SITC)'s 35th Anniversary Annual Meeting.
“Achieving an overall response rate of 30% 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,” Paolo A. Ascierto, MD, director of the Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy at the National Tumor Institute Fondazione G. Pascale in Naples, Italy, said in a press release. “The data reported, in addition to its ease of use, demonstrate the potential of [tavokinogene telseplasmid] 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.”
Notably, tavokinogene telseplasmid previously received fast track designation from the FDA for the treatment of metastatic melanoma following progression on pembrolizumab or nivolumab.
OncoSec Announces Positive Interim Data from KEYNOTE-695 Trial in Anti-PD-1 Checkpoint Refractory Metastatic Melanoma at SITC 2020 [news release]. Pennington, NJ and San Diego. Published November 9, 2020. Accessed November 9, 2020. https://www.prnewswire.com/news-releases/oncosec-announces-positive-interim-data-from-keynote-695-trial-in-anti-pd-1-checkpoint-refractory-metastatic-melanoma-at-sitc-2020-301168680.html