Combination Approach

Rationale for Combination Approach

The majority of patients with solid tumors who have been treated with anti-PD-1/PD-L1 therapies do not respond to treatment: this is one of the great challenges in oncology today. OncoSec believes ImmunoPulse® IL-12 may address this unmet medical need by increasing the proportion of patients who will respond to anti-PD-1 and other checkpoint therapies.

 

Tumor Type

Anti-PD1/PDL1 mAb Non-Response

Melanoma

~ 60 – 80%

Triple Negative Breast (TNBC)

~ 70% – 82%

Renal Cell Carcinoma (RCC)

~ 71%

Lung Carcinoma (NSCLC)

~ 79 – 83%

Head and Neck (H&N)

~ 80% 1

Bladder

~ 84% 2

1 Patients were preselected by Merck PD-L1 IHC assay
2 11% in PD-L1 (Roche) negative: 43% in PD-L1 + population

How it Works

Certain cancers can bypass or hide from the immune system by engaging an immune checkpoint called PD-1, which is a protein found on T-cells. PD-1 represents an “off-switch” which cancers can exploit to escape from T-cells, which are critical to the immune system’s anti-tumor attack. New treatments, called checkpoint inhibitors, block these “off-switches” and help keep T-cells in attack mode to fight cancer cells.

 

Patients who possess “switched-off” anti-tumor CD8+ T-cells in their tumors (i.e. increased tumor-infiltrating lymphocytes, or TILs) are most likely to respond to therapy with anti-PD1 or anti-PD-L1 drugs. However, studies show that these TILs – the target cell for T-cell checkpoint agents – are lacking in the majority of patients. As a result, anti-PD-1 non-responders constitute the majority of patients with solid tumors.

 

Pre-clinical data indicates that local delivery and expression of ImmunoPulse® IL-12 promotes tumor immunogenicity and increases TILs. As a pro-inflammatory cytokine, IL-12 can promote the recruitment of T-cells to the tumor. By driving T-cells or TILs into the tumor microenvironment, ImmunoPulse® IL-12 may enhance response to anti-PD-1 and convert anti-PD-1 non-responders to responders.

Additional Resources

The following scientific resources provide additional information about immune checkpoint therapies in cancer immunotherapy.
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