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: A An NRG Oncology/Gynecologic Oncology Group Study 0229N
Article
Makker, Vicky, Filiaci, Virginia L., Chen, Lee-may, Darus, Christopher J., Kendrick, James E., Sutton, Gregory, Moxley, Katherine, Aghajanian, Carol
funding text
Dr. Virginia Filiaci reports grants and non-financial support from National Institutes of Health, National Cancer Institute, other from Acceleron Pharma, Inc., during the conduct of the study. Additionally, Dr. Carol Aghajanian received an honorarium as a one-time ad board member in addition to travel expenses. Dr. Aghajanian also received funding for travel from Abbvie for clinical trial planning meetings. All other authors on this manuscript have no conflicts of interest to disclose.
abstract
Objective. This two-stage phase II study assessed activity of single agent dalantercept in patients with recurrent/persistent endometrial carcinoma (EMC). Methods. Eligible 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. Results. All 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 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% Cl: 1.4-3.2) and 14.5 months (90% CI: 7.0-17.5), respectively. Conclusions. Dalantercept has insufficient single agent activity in recurrent EMC to warrant further investigation at this dose level and schedule. (C) 2015 Elsevier Inc. All rights reserved.