OncoSec and Merck to Launch Phase 3 Trial of IL-12 Gene Therapy TAVO™ Combined with KEYTRUDA® for Metastatic Melanoma

Recently, OncoSec Medical announced that it has entered into a clinical trial collaboration with MSD to conduct a global Phase 3 clinical trial evaluating the efficacy of combining its IL-12 DNA plasmid therapy, TAVO (tavokinogene telseplasmid), with the anti-PD-1 therapy Keytruda for the treatment of patients with advanced metastatic melanoma. TAVO is a potential first-in-class anticancer gene therapy, and this trial will support a submission for accelerated approval from the FDA.

Although immune checkpoint inhibitors have become a cornerstone of cancer therapy, many patients still remain unresponsive to them. According to OncoSec Medical, 70% of solid tumors are "cold" tumors, which contain immunosuppressive cells and exhibit minimal T cell infiltration, thereby limiting the efficacy of immune checkpoint inhibitors.

IL-12 is a crucial mediator of intercellular communication between dendritic cells/macrophages and effector T cells/natural killer cells. TAVO, developed by OncoSec, is an intratumoral gene therapy consisting of a DNA plasmid that encodes the IL-12 protein. Following intratumoral injection, electroporation is utilized to facilitate cellular uptake of the plasmid.

Plasmids internalized by cells can transform tumor cells into "factories" for IL-12 production, stimulating natural killer (NK) cells and T cells to produce interferon-gamma (IFN-γ). IFN-γ then stimulates dendritic cells to produce more IL-12, forming a positive feedback loop. This enhances tumor immunogenicity and stimulates the infiltration of more effector T cells into the tumor.

Locally injected TAVO not only enhances the immunogenicity of the injected tumor, but also enables activated T cells to migrate to other parts of the body to eliminate distant tumors.

▲ Schematic of TAVO's Mechanism of Action (Image source: Reference [2])

The combination of TAVO and Keytruda has yielded positive results in a pivotal Phase 2b clinical trial for the treatment of patients with metastatic melanoma. Among 54 evaluable patients, 5 achieved complete tumor disappearance.

▲ Preliminary results from a Phase 2b clinical trial of TAVO in combination with Keytruda in patients with metastatic melanoma (Image source: Reference [2])

Under the agreement, both parties will initiate a Phase 3 clinical trial designated KEYNOTE-C87, expected to enroll approximately 400 patients with unresectable or metastatic melanoma who have developed resistance to checkpoint inhibitor therapy.

Note: The original text has been abridged.

References:

[1] OncoSec Enters into a Collaboration Agreement with Merck for a Pivotal Global Phase 3 Study, KEYNOTE-C87, of TAVO^™ Combined with KEYTRUDA^® for Late-Stage Metastatic Melanoma. Retrieved July 7, 2021, from https://ir.oncosec.com/press-releases/detail/2089/oncosec-enters-into-a-collaboration-agreement-with-merck

[2] Oncosec corporate presentation. Retrieved July 7, 2021, from https://d1io3yog0oux5.cloudfront.net/_017db190c1353a7a92bb57d41e106809/oncosec/db/259/1933/pdf/OncoSec+Corporate+Deck+2021+March+as+of+4.8.2021.pdf

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