Targovax plans checkpoint combo trial after posting early data on oncolytic virus

Targovax has shared data from an early-phase trial that administered ONCOS-102 to mesothelioma patients. The response rate was lower in the ONCOS-102 arm than in the control cohort, but Targovax saw positives elsewhere, leading it to outline plans to pair the drug with a checkpoint inhibitor.

ONCOS-102 is an adenovírus-based cancer therapy that Targovax thinks can improve on treatment options available to patients with pleural mesothelioma, a type of cancer that affects the lining of the lungs. That belief is underpinned by preclinical evidence that ONCOS-102 directly kills cancer cells and triggers an innate immune response. 

The phase 1/2 trial provides an early test of that hypothesis. After a six-subject safety lead-in stage, Targovax randomized 25 mesothelioma patients to receive either ONCOS-102 plus chemotherapy or just the standard-of-care treatment.

In the cohort of patients who received ONCOS-102 as a first-line treatment, the overall response rate was 30%, as compared to 33% in the control group that just received chemotherapy. The trial also linked chemotherapy to a higher response rate in second-line patients. In that population, the rates for ONCOS-102 and standard of care were 11% and 60%, respectively.

Targovax addressed the difference in a statement to disclose the data, noting that the 60% response rate “is far above previous results and experience in clinical practice.” The small size of the clinical trial, which enrolled 31 patients, means anomalous results are possible.

In the absence of compelling response results, Targovax pointed to other aspects of the data set to make its case for the potential of ONCOS-102. As it stands, progression-free survival in people who received ONCOS-102 as a first-line treatment is 8.9 months, putting it ahead of the control group and results from previous studies. However, given that many patients remain censored, the relevance of the figure is questionable.

Targovax also highlighted increased CD8+ T-cell infiltration in patients who received ONCOS-102. That finding may suggest ONCOS-102 supports immune attacks on tumors. Whether that translates into improved outcomes remains to be seen. Some patients with minimal T-cell infiltration had partial responses. Another patient with relatively high T-cell infiltration progressed after treatment.

A clearer picture may emerge when the program progresses to its next stage. Targovax wants to test ONCOS-102 in combination with a checkpoint inhibitor and is in talks with a pharma partner about the study. That trial could show whether ONCOS-102 can improve T-cell infiltration and, in doing so, make checkpoint inhibitors more broadly efficacious.