Phase II evaluation of dalantercept, a soluble recombinant activin receptor-like kinase 1 (ALK1) receptor fusion protein, for the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group Study 0229N

•Angiogenesis plays a role in endometrial cancer progression and prognosis.•Dalantercept binds BMP9/BMP10 and prevents signaling through activin receptor-like kinase, which results in inhibition of the maturation phase of angiogenesis.•Single agent dalantercept in advanced/recurrent endometrial cancer has insufficient activity to warrant further investigation as a monotherapy in this disease.

ObjectiveThis two-stage phase II study assessed activity of single agent dalantercept in patients with recurrent/persistent endometrial carcinoma (EMC).MethodsEligible patients had persistent/recurrent EMC after 1-2 prior cytotoxic regimens, measurable disease (RECIST 1.1), and GOG performance ≤ 2. Dalantercept 1.2 mg/kg subcutaneous was administered once every 3 weeks until disease progression (PD)/development of prohibitory toxicity. Primary objectives were to estimate the proportion of patients with persistent/recurrent EMC, who survive progression-free without receiving non-protocol therapy (TPFS) for at least 6 months and to estimate the proportion having objective tumor response.ResultsAll 28 enrolled patients were eligible and evaluable. Median age: 62 years. Most common histologies: 32% Grade 1/2 endometrioid and 54% serous tumors. Prior treatment: 1 or 2 regimens in 82% and 18% of patients, respectively. Eighteen patients received prior radiation therapy. Patients received 1-12 cycles of dalantercept, and 46% of patients received ≤ 2 cycles. The most common adverse events (AE) were fatigue, anemia, constipation and peripheral edema. Grade 3/4 AEs occurred in 39% and 4% of patients. One grade 5 gastric hemorrhage in a patient with a history of radiation fibrosis/small bowel obstruction was deemed possibly dalantercept-related. All patients are off study: 86% for PD. No ORs were observed; 57% had stable disease and 11% had TPFS > 6 mos. Median progression-free and overall survival: 2.1 months (90% CI: 1.4-3.2) and 14.5 months (90% CI: 7.0-17.5), respectively.ConclusionsDalantercept has insufficient single agent activity in recurrent EMC to warrant further investigation at this dose level and schedule.