KEYNOTE-695 Interim Data - Pembrolizumab (Keytruda) combined with TAVO (intratumoral plasmid IL-12 ~ tavokinogene telseplasmid)

In July of 2020 I posted on the combo of TAVO and Pembro here -  Intratumoral (intralesional) therapy and a new guy in town: IL-12 Plasmid Transfection (tavo) with pembro  That is:  "intratumoral plasmid IL-12 (tavokinogene telseplasmid; "tavo") electroporation combined with pembrolizumab".

Now there is this from November 2020 ~

OncoSec Announces Positive Interim Data from KEYNOTE-695 Trial in Anti-PD-1 Checkpoint Refractory Metastatic Melanoma at SITC 2020

The report notes:

-- 30% overall response rate (ORR) and 6% complete response (CR) rate achieved 
-- 35% ORR achieved in patients with Stage IV M1c or M1d disease 
-- TAVO + pembrolizumab demonstrated durable responses for up to two years

TAVO + KEYTRUDA led to a 30% ORR in the first 54 out of 100 planned patients. This interim investigator assessed ORR is much higher than the primary efficacy endpoint for the study, which is a 20% ORR determined by blinded independent review.  The data were selected for a Poster Walk discussion and will be additionally presented in the virtual Poster Hall on Wednesday, November 11 and Friday November 13 and as part of a Company Symposium on November 11th 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. The data reported, in addition to its ease of use, demonstrate the potential of TAVO 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, M.D., Director of the Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy at the National Tumor Institute Fondazione G. Pascale in Naples, Italy.

Key highlights of KEYNOTE-695 include:

• Of the first 54 out of 100 planned patients ~

• ORR was 30% (95%CI [18.0%, 43.6%]) (16/54)

• Complete response rate was 6% (3/54)

• All responses were confirmed by scans taken no earlier than after 6 months on study

• 9% (5/54) patients had 100% reduction of target lesions

• ORR was 35% (n=6/17) in patients with Stage IV M1c/M1d disease

• ORR was 40% (n=6/15) in patients with prior exposure to ipilimumab

• Median duration of response (mDOR) is currently 12.2 months

• Median study follow-up was 13.5 months

• Excellent safety profile resulting from intramural treatment approach

• Only 5.4% Grade 3 treatment-related AEs

• No grade 4/5 treatment-related AEs

• This study enrolled rapidly progressing patients with a short interval of 1.2 months (median) between the last dose of anti-PD-1 and study treatment

Adil Daud, M.D., a  Professor of Medicine at The University of California, San Francisco, Director of the Melanoma Clinical Research, and lead author of the study added, "the TAVO-electroporation (TAVO-EP) delivery system works by optimizing cellular uptake of DNA-based IL-12 in the tumor microenvironment, leading to local, sustained production of IL-12 in the tumor, where it matters, with negligible systemic exposure.  This recruits and primes immune cancer-fighting cells in the tumor leading to systemic immune responses without systemic toxicity. The totality of the safety and efficacy data establishes TAVO-EP as a best-in-class intratumoral therapy."

Daniel O'Connor, Chief Executive Officer of OncoSec, added "Patients with recurrent metastatic melanoma are in great need of effective treatment options. We believe this data demonstrates not only strong levels of efficacy, but also very low treatment related adverse events with the TAVO + pembrolizumab combo. This, combined with its ease of administration to accessible lesions within minutes in an outpatient setting, plus TAVO's low-cost/simple manufacturing process and its off-the-shelf availability, build a strong case that the TAVO + pembrolizumab combination, in a real-world setting, could equip clinicians with more options for their patients."

Results are still not as good as those achieved with the ipi/nivo combo.  But, for those who can't tolerate that treatment or remain in need of additional treatment, this combo may be a viable option.  For what it's worth! - c