title: 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.
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 1.2mg/kg subcutaneous was administered once every 3weeks 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 6months and to estimate the proportion having objective tumor response.
  
  
  RESULTS
  All 28 enrolled patients were eligible and evaluable. Median age: 62years. 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 ≤2cycles. 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: 2.1months (90% CI: 1.4-3.2) and 14.5months (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.
authors.affiliation: Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States. Electronic address: makkerv@mskcc.org.
authors.forename: Vicky
authors.initials: V
authors.lastname: Makker
authors.affiliation: NRG Oncology Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Filiaci
authors.affiliation: Obstetrics and Gynecology, University of California, San Francisco, San Francisco, CA 94115, United States.
authors.forename: Lee-May
authors.initials: LM
authors.lastname: Chen
authors.affiliation: Gynecologic Oncology, Maine Medical Center, Scarborough, ME 04074, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Darus
authors.affiliation: Gynecologic Oncology, Florida Hospital Cancer Institute Orlando, FL 32804, United States.
authors.forename: James E
authors.initials: JE
authors.lastname: Kendrick
authors.affiliation: Gynecologic Oncology, St. Vincent Hospitals and Health Services, Indianapolis, IN 46269, United States.
authors.forename: Gregory
authors.initials: G
authors.lastname: Sutton
authors.affiliation: Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States.
authors.forename: Katherine
authors.initials: K
authors.lastname: Moxley
authors.affiliation: Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States.
authors.forename: Carol
authors.initials: C
authors.lastname: Aghajanian
mesh_terms: D030301:Activin Receptors, Type II / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D030301:Activin Receptors, Type II; C000591618:ALK1-Fc fusion protein, human
keywords: ALK-1; Dalantercept; Recurrent endometrial cancer