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Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

Combination therapy shows positive clinical response in treatment-resistant melanoma patients

Preliminary results of a Phase 1 clinical trial testing a combination of Keytruda, an immune checkpoint inhibitor with Targovax‘s immune activator ONCOS-102 show signs of positive outcome in checkpoint-inhibitor-resistant melanoma patients.

The trial is being conducted at the Memorial Sloan Kettering Cancer Center in New York, Fox Chase Cancer Center in Philadelphia, and University of Maryland in Baltimore, in advanced or surgery-ineligible melanoma patients whose tumor continued to progress despite treatment with Keytruda.

The study is carried out in 2 parts. In part 1, patients received three injections of Targovax‘s immune activator, ONCOS-102, directly into the tumor during the first week. On day 22, Keytruda was given every three weeks and patients were followed until week 24.

ONCOS-102 consists of a harmless virus armed with an immune activator molecule. It is engineered to kill tumor cells by triggering an anti-tumor response in the body. Keytruda is an antibody that targets and blocks the activity of a protein, PD-1 receptor, found on the surface of immune cells which prevents cancer cells from being killed by immune cells.

Early results showed that patients who became resistant to immune checkpoint inhibitors re-gained the susceptibility to such treatments after receiving ONCOS-102. The combination reduced tumor size in three of the nine patients enrolled, including one patient whose disease completely disappeared. The sequential treatment was well-tolerated and led to encouraging signs of efficacy, with an overall response rate of 33%.

Additional data revealed that ONCOS-102 triggered pro-inflammatory cytokines against tumors in all nine patients and led to an increase in tumor-infiltrating T-cells. Immune cells armed against tumor proteins were also detected in circulation in four patients, which further supports ONCOS-102’s ability to activate immune response against tumors.

While Part 1’s goal was to assess safety, the ongoing Part 2 will evaluate the safety and efficacy of a more intensive treatment. Patients will receive four injections of ONCOS-102, followed by a combination of ONCOS-102 and Keytruda. The idea behind the intensified dosing regime is that the company believes that patients will benefit from receiving more ONCOS-102 injections over a longer period of time and thus could yield more clinical responses.

Magnus Jäderberg, CMO of Targovax commented: “We are very pleased to confirm our hypothesis that ONCOS-102 has the potential to immune activate checkpoint-inhibitor-resistant patients to respond to PD-1 blockade with Keytruda. It is promising to see this level of clinical responses after only three ONCOS-102 injections, including a complete response, which is rare in this heavily pre-treated patient population”.

Source: ONCOS-102, Keytruda Combo May Reduce Tumor Size in Treatment-resistant Melanoma, Early Trial Data Show; Website

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