Abstract OT2-07-04: A phase 2 study of ONC201 in recurrent/refractory metastatic breast cancer and advanced endometrial carcinoma
Authors: Gatti-Mays ME , Greer Y , Steinberg S , Soltani S , Collins J , Olson M , Ojemuyiwa M , Annunziata C , Lee J-M , Nunes A , Lipkowitz S , Zimmer A 
Published: February 2018

Abstract
Background: Advanced breast cancer (BC) and endometrial cancer (EC) have limited treatment options with no treatments improving survival. ONC201 is the founding member of a novel class of anticancer drugs called impiridones. The drug is orally bioavailable and crosses the blood brain barrier. Preclinical studies have demonstrated that ONC201 selectively kills various cancer cells, including all subtypes of BC and EC, while having little effect on normal cells. An on-going Phase 1 study of ONC201 has demonstrated clinical benefit in some solid tumors, including EC and glioblastomas.
Trial Design: Phase 2 single arm study of ONC201 with 3 cohorts: Cohort 1, female and male hormone receptor positive breast cancer (HR+BC); Cohort 2, female and male triple negative breast cancer (TNBC); and Cohort 3, EC. All patients will receive ONC201 at the recommended Phase 2 dose of 625mg by mouth q7 days (1 cycle = 28 days). Patients will undergo a baseline biopsy as well as a biopsy after 5 doses of ONC201 (C2D2). Patients will be evaluated for response every two cycles (8 weeks) by RECIST 1.1.
Eligibility Criteria: Measurable disease with &gt;1 biopsiable lesion, willing to undergo biopsies. Cohort 1 (HR+BC) requires prior treatment with &gt;2 lines of hormonal treatment. No prior treatment required for the other cohorts. Patients must have ECOG 0-1 and adequate organ function. Patients with asymptomatic or brain metastases treated &gt; 4 weeks from study entry are eligible. Exclusion criteria include: symptomatic CNS metastases, radiotherapy ≤ 4 weeks from study entry, HIV, Hepatitis B or Hepatitis C.
Specific Aims: Primary objectives for this study are progression free survival (PFS) at 8 months for Cohort 1 (HR+BC) and overall response rate (ORR) for Cohorts 2 and 3 (TNBC and EC). Secondary objectives include safety, clinical benefit rate (CBR = partial response + complete response + stable disease), and overall survival.
Statistical Methods: This study has been designed to pause prior to full accrual to allow for evaluation of futility prior to proceeding to full accrual. In Cohort 1, if &gt;1 of 5 patients is progression-free at 8 months, then we will recruit up to 24 patients. In Cohort 2, if &gt;2 of 10 patients has clinical benefit then we will recruit up to 29 patients. For Cohort 3, if 1 of 13 patients has clinical benefit, then we will recruit up to 25 patients. Additional evaluations of tumor or blood samples performed will be done in an exploratory fashion, with results presented without any formal adjustment for multiple comparisons.
Target Accrual: 24 patients with HR+BC, 29 patients with TNBC, and 25 patients with EC.This trial will open Summer 2017 at the National Institutes of Health (Bethesda, MD).
Contact Information: Principal Investigator Alexandra S Zimmer, MD; alexandra.zimmer@nih.gov
Citation Format: Gatti-Mays ME, Greer Y, Steinberg S, Soltani S, Collins J, Olson M, Ojemuyiwa M, Annunziata C, Lee J-M, Nunes A, Lipkowitz S, Zimmer A. A phase 2 study of ONC201 in recurrent/refractory metastatic breast cancer and advanced endometrial carcinoma [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-07-04.