This study was terminated due to a change in the Sponsor's corporate priorities. The decision to terminate the study was not based on any safety concerns.

This was a Phase 2, Simon two-stage, non-randomized, open-label, 2-arm trial of dordaviprone (ONC201) in women with metastatic or recurrent Type II endometrial cancer who failed at least 1 prior chemotherapy regimen. Patients with histologically confirmed Type II endometrial cancer, including but not limited to serous, clear cell, carcinosarcoma, adenosquamous, and mixed histologies were eligible.

The primary objective of this study was to determine the efficacy of dordaviprone (ONC201) in metastatic type II endometrial cancer.

Note: This study was completed by predecessor company, Oncoceutics, Inc.

This study included 3 arms: Arm A, Arm B, and Arm C. Dordaviprone (ONC201) was to be administered as a dose of 625 mg by mouth, once or twice each week until disease progression, unacceptable toxicity, or if the patient discontinued for any other reason.

For Arm A and Arm B, ONC201 administration occurred on Days 1, 8, and 15 of each 3-week cycle. For Arm C, ONC201 administration occurred on Days 1, 2, 8, 9, and 15, and 16 of each 3-week cycle.

All patients in Arm A had a biopsy of their tumor one day after the second dose of dordaviprone (ONC201) on Cycle 1, Day 9. All patients in Arm C had a biopsy of their tumor one day after the fourth dose of dordaviprone (ONC201) on Cycle 1, Day 10.

Assessments of objective tumor response were conducted using RECIST version 1.1. Safety was assessed through the reporting of adverse events, measurement of vital signs, electrocardiograms, and clinical laboratory results.

Before the study was terminated, a total of 27 patients were enrolled and received at least 1 dose of dordaviprone (ONC201): 10 patients in Arm A, 14 patients in Arm B, and 3 patients in Arm C.

Inclusion Criteria:

A patient had to meet all of the following criteria to be eligible to participate in the study:

1. Had histologically confirmed metastatic or recurrent Type II endometrial cancer (serous, clear cell, carcinosarcoma, adenosquamous, and mixed histologies). For patients with tumors that had mixed histologies, the tumor should have had evidence of some tumor cells with Type II endometrial cancer features.

2. Must have had measurable disease, defined as at least 1 lesion that could be accurately measured in at least 1 dimension in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

3. Had availability of at least 12 unstained slides from archival formalin-fixed paraffin-embedded (FFPE) tumor tissue. Available archived tissue biopsies were provided for correlative studies.

4. For Arm A and Arm C, patients must have had disease that was amendable to biopsy and must have been willing to provide consent for a tumor biopsy at baseline (within 30 days of beginning ONC201) an at least 1 on-treatment tumor biopsy.

5. Must have had radiographic disease progression after at least 1 line of systemic cytotoxic therapy for metastatic disease or with progression within 12 months of completing adjuvant chemotherapy.

6. Were aged ≥18 years.

7. Had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

8. Must have had adequate bone marrow, hepatic and renal function, as defined below:

   • Leukocytes: ≥3000/mcL
   • Absolute neutrophil count: ≥1500/mcL
   • Platelets: ≥100,000/mcL
   • Total bilirubin: ≤1.5 upper limit of normal (ULN)
   • Aspartate aminotransferase/Alanine aminotransferase (SGOT/SGPT): ≤2 ULN
   • Creatinine: ≤1.5 ULN OR
   • Creatinine clearance: ≥60 mL/min/1.732 for patients with creatinine levels above ULN calculated using Calvert formula

9. Had a life expectancy of at least 3 months.

10. Had the ability to understand and willingness to sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) consent document.

11. Must have been surgically sterile or postmenopausal or must have agreed to use effective contraception during the period of the trial and for at least 90 days after completion of treatment.

Exclusion Criteria:

A potential patient who met any of the following criteria was ineligible to participate in the study:

1. Had any prior treatment with ONC201.
2. Had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who had not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier.
3. Patients who had not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤2 from related toxicity to all prior therapies were excluded. Patients with non-serious AEs such as alopecia, fatigue, weakness, loss of appetite, and nausea that were non-significant were not excluded.
4. Had any other prior malignancy from which the patient had been disease-free for less than 3 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site.
5. Were unable to swallow capsules.
6. Had impairment of gastrointestinal (GI) function or GI disease that may have significantly altered the absorption of ONC201 (uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
7. Were receiving any other investigational agents.
8. Patients with symptomatic brain metastases were excluded. Patients with asymptomatic and treated central nervous system (CNS) metastases may have participated in this trial. The patient must have completed any prior treatment for CNS metastases >28 days prior to study entry including radiotherapy or surgery. Steroids for the treatment of brain metastasis were not permitted, and patients must have been stable off steroid treatment for 4 weeks prior to enrollment.
9. Had uncontrolled intercurrent illness including but not limited to ongoing or active infection. Or any of the following in the 6 months previous to enrollment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
10. Had active inflammatory GI disease, chronic diarrhea (unless related to underlying malignancy or prior related treatment) or history of abdominal fistula, GI perforation, peptic ulcer disease, or intra-abdominal abscess within 6 months prior to study enrollment. Gastroesophageal reflux disease under treatment with proton pump inhibitors was allowed.
11. Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy.
12. Had active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may have increased the risk associated with study participation or study drug administration or may have interfered with the interpretation of study results, or in the judgement of the Investigator, would have made the patient inappropriate for entry into the study.
13. Were pregnant or breast feeding.
14. Had known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias, or bradycardia, unless arrhythmia was controlled and after cardiology had cleared patient to receive ONC201. Was receiving therapeutic agents known to prolong QT interval; however, the use of Zofran was permitted. Had a history of congestive heart failure or myocardial infarction or stroke in the 3 months prior to enrollment.
15. Concomitant use of potent cytochrome P450 (CYP) A4/5 inhibitors or inducers during the treatment phase of the study and within 2 hours prior to starting study drug administration.

From the time/date of initiation of study treatment through 30 days following cessation of study treatment (32 months)

Note: The progression of cancer under study was not considered an adverse event.

Note: This study was terminated due to a change in corporate priorities. The decision to terminate the study was not based on any safety concerns with dordaviprone (ONC201).