The size of tumors in patients with recurrent ovarian cancer seems to predict responses to a triple combination treatment composed of IMV‘s lead candidate DPX-Survivac, Incyte’s experimental epacadostat, and low-dose chemotherapy, a Phase 1/2 trial shows.
Among patients with smaller tumors at baseline — 5 centimeters or less — the treatment reduced tumors in 67% and controlled the disease in an additional 16%.
The findings were presented at the ESMO Immuno-Oncology 2018 Congress in Geneva, Switzerland, in a poster titled “New clinical data from the DeCidE1 trial: Results on DPX-Survivac, low dose cyclophosphamide (CPA), and epacadostat (INCB024360) in subjects with advanced recurrent epithelial ovarian cancer.”
DPX-Survivac is a cancer vaccine made of small fractions of the survivin protein. This protein is found is most cancer types at much higher levels than normal and plays a key role in supporting tumor blood vessel growth and promoting resistance to anti-cancer therapies.
The therapy, administered as an injection under the skin, works by triggering a strong immune response against cancer cells producing the survivin protein, causing them to die.
Epacadostat is a potent, selective oral IDO1 inhibitor. Belonging to the growing class of checkpoint inhibitors, such as CTLA-4, PD-1, and PD-L1 antibodies, IDO pathway inhibitors can restore immune responses, suppressing tumor growth.
The Phase 1b/2 trial – called DeCidE1 (NCT02785250) – was designed to test a combination of DPX-Survivac, epacadostat and low-dose cyclophosphamide in ovarian cancer patients who received surgery and any number of prior chemotherapies.
Its main goals are to determine the safety of the combination, whether patients develop T-cells specific to the survivin protein, and whether these T-cells are entering the tumors. Secondary measures include objective response rate, duration of response, time to progression, and overall survival.
To date, the Phase 1b part of the trial included 53 patients, who received one of two doses of epacadostat — 100 mg or 300 mg — along with the other two therapies.
Overall, the treatments were well-tolerated and induced the expansion of survivin-specific T-cells. Efficacy data from the first 32 evaluable patients also showed that durable responses correlated with T-cell infiltration into tumors. However, a lower tumor size was predictive of better responses.
Indeed, while 67% of patients with non-bulky disease — with a baseline tumor size of 5 cm or less — experienced a tumor regression of at least 30%, only 15% of patients with larger tumors reached such outcome. The rate of patients benefiting from the treatment was also better among those with smaller tumors — 83.3% versus 65%.
Interestingly, researchers found that treatment with 300 mg epacadostat resulted in poorer responses compared to the 100-mg dose. Based on the findings, IMV and Incyte had agreed to stop dosing patients with epacadostat and continue studying a combination of DPX-Survivac and cyclophosphamide only in the Phase 2 trial.
Nonetheless, researchers reported durable clinical benefits, lasting more than two years, which was longer than patients had lived without disease progression following their last line of chemotherapy.
“This data set provided meaningful information on how the potential benefits of DPX-Survivac may best be translated to patients, including the connection between tumor regressions and T-cell infiltration in the tumor microenvironment,” Frederic Ors, chief executive officer at IMV, said in a press release. “We believe that DPX-Survivac is the first targeted T-cell therapy to induce significant tumor regressions in challenging tumors such as those seen in ovarian cancer.”
He added, “We remain committed to developing DPX-Survivac for patients with significant unmet medical needs, and look forward to our upcoming discussions with regulatory authorities in the USA, Canada and Europe.”