The DART Phase 2 clinical trial, assessing Acceleron Pharma’s dalantercept in combination with Pfizer’s Inlyta (axitinib) in advanced renal cell carcinoma (RCC) patients, has failed to demonstrate an improvement in patients’ time to disease progression or death, compared to Inlyta alone, which was the trial’s primary endpoint. The results prompted the company to discontinue the development of dalantercept.
Dalantercept is an investigational protein that was designed to inhibit the formation of mature and functioning vessels required for tumor growth and progression.
The randomized, placebo-controlled DART study (NCT01727336) aimed to evaluate the therapeutic potential of dalantercept plus Inlyta for the treatment of advanced RCC.
The study was conducted in two parts. Part 1 was a dose-escalation study assessing the safety and tolerability of the combo treatment in patients who had been previously treated with one to three lines of therapy. Part 2 was a randomized, double-blind study assessing the effectiveness of the combination in patients who had progressed following treatment with an approved VEGF receptor tyrosine kinase inhibitor, such as Avastin (bevacizumab) or Votrient (pazopanib).
Among the 131 patients included in the study, only 119 were included in the treatment efficacy evaluation. Among these, 58 patients received subcutaneous injection of dalantercept once every three weeks combined with oral, twice-daily Inlyta, and 61 patients were treated with a placebo control plus Inlyta.
The combined therapy failed to meet the primary outcome measure, defined as an improvement in progression-free survival (PFS). Patients treated with the combination had a median PFS of 6.8 months, compared to the reported 5.6 months in the placebo plus Inlyta group.
Dalantercept also did not improve the time to disease progression among patients who had received two or more prior systemic anti-cancer therapies, one of the trial’s secondary endpoints. Patients treated with dalantercept had a median PFS of 8.1 months, compared to 7.0 months in the control arm, a result that did not reach statistical significance.
Researchers also showed that more patients on the control arm responded to treatment (25 percent) than those on the dalantercept arm (19 percent).
Regarding safety, the incidence of treatment-related side effects was very similar between the two groups, and were consistent with previous reports.
“We designed a robust Phase 2 study to evaluate the efficacy of dalantercept in combination with anti-VEGF therapy in advanced renal cell carcinoma patients whose disease has progressed on prior anti-VEGF therapy,” Habib Dable, president and CEO of Acceleron, said in a press release.
“We are disappointed by the results, given the need for new agents that improve outcomes for patients with advanced RCC. We would like to thank the patients, caregivers, investigators, and our team who made the DART study possible. Based on the lack of efficacy, we are discontinuing the development of dalantercept,” Dable added.