US-based OncoSec Medical Inc., (OTCMKTS: ONCSQ), majority-owned by China-based Grand Pharmaceutical Group Ltd (HKG: 0512), has revealed disappointing data from a crucial pivotal Phase II trial assessing the firm’s lead DNA drug candidate TAVO-EP (tavokinogene telseplasmid) combined with the programmed death-1 (PD-1) monoclonal antibody Keytruda (pembrolizumab) as a treatment for melanoma. The combination failed to achieve the primary endpoint of improved overall response rate (ORR), leading to a significant drop in OncoSec’s shares.
Phase II KEYNOTE-695 Trial Details and Outcomes
The combo regimen was being assessed in the Phase II KEYNOTE-695 trial, a global, open-label single-arm study focusing on patients with unresectable or metastatic (Stage 3/4) melanoma with disease progression after at least 12 weeks prior anti-PD-1 therapy (pembrolizumab or nivolumab). In 98 evaluable patients, the ORR for the TAVO+Keytruda regimen was only 10.2%, well below the 17% pre-set target for the study. The disease control rate (CR + PR + SD) was 35.7%, with a durable response rate of ≥24 weeks at 8.2% and a median duration of response of 25.5 months.
Setback for OncoSec and Future Focus
The trial failure is a significant setback for OncoSec, which had previously reported around a 30% ORR in earlier trials. OncoSec noted that the focus will now shift to the application of TAVO-EP in the neoadjuvant melanoma setting, following strong evidence from an earlier investigator-initiated trial that the treatment can generate a strong clinical response.
TAVO-EP: A DNA-Based IL-12 Treatment
TAVO-EP is a DNA-based interleukin-12 (IL-12) administered directly into the tumor using an electroporation (EP) gene delivery system, designed to increase the permeability of the cell membrane and facilitate uptake of IL-12 coded DNA into cells. In October last year, OncoSec decided to cut 45% of its workforce to focus resources solely on TAVO-EP’s development in melanoma.
Investment and Ongoing Development
OncoSec is majority-owned by China Grand and China Grand subsidiary Sirtex following a USD 30 million investment that closed in February 2020, providing the necessary funding for TAVO-EP’s ongoing development.-Fineline Info & Tech
