ONC201 and Atezolizumab in Obesity-Driven Endometrial Cancer

NCT ID: NCT05542407

Last Updated: 2026-01-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-23
• Study Completion Date: 2028-07-31

Brief Summary

Endometrial cancer (EC) is the fourth most common cancer in United States women, and alarmingly, the frequency and mortality from EC continues to rise, in part due to the obesity epidemic. Obese women with EC have a 6.3-fold increased risk of death from this disease, as compared to their non-obese counterparts. Patients with advanced/recurrent EC are unlikely to be cured by surgery, conventional chemotherapy (paclitaxel + carboplatin is the standard first-line treatment), radiation, or a combination of these. Thus, new treatments for EC are desperately needed as well as a better understanding of the impact of obesity on EC biology and treatment.

The purpose of this study is to test the safety of a combination of treatments, atezolizumab and ONC201, given based on body weight, to treat endometrial cancer. Using the combination of atezolizumab and ONC201, has not been approved by the Food and Drug Administration (FDA) for the treatment of endometrial cancer. This clinical trial will examine the treatment of atezolizumab + ONC201 in obese and non-obese subjects with metastatic/recurrent EC.

Conditions

Endometrial Cancer; Metastasis; Endometrioid Endometrial Cancer; Carcinosarcoma; Serous Adenocarcinoma of Endometrium (Diagnosis); Clear Cell Endometrial Carcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Cell Adenocarcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Obese

Subjects with BMI \> 30 kg/m2

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

10 mg/kg- 20 mg/kg Atezolizumab will be administered by intravenous, on day 1 of each 21-day cycle.

ONC201

Intervention Type: DRUG

375 mg once weekly - 625 mg ONC201 will be administered orally, once or twice weekly.

Non-Obese

Subjects with BMI ≤ 29.9 kg/m2

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

10 mg/kg- 20 mg/kg Atezolizumab will be administered by intravenous, on day 1 of each 21-day cycle.

ONC201

Intervention Type: DRUG

375 mg once weekly - 625 mg ONC201 will be administered orally, once or twice weekly.

Interventions

Atezolizumab

10 mg/kg- 20 mg/kg Atezolizumab will be administered by intravenous, on day 1 of each 21-day cycle.

Intervention Type: DRUG

ONC201

375 mg once weekly - 625 mg ONC201 will be administered orally, once or twice weekly.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Ability to understand and willingness to sign a written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.

2. Age ≥ 18 years at the time of consent.

3. ECOG Performance Status of 0, 1, or 2

4. Histologically confirmed metastatic or recurrent EC (endometrioid, carcinosarcoma, serous, clear cell, adeno-squamous and mixed histologies).

5. Subjects must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria

6. Must have 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.

7. Life expectancy of at least 3 months.

8. Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 72 hours prior to initiating study treatment.

Exclusion Criteria

1. Prior treatment with ONC201.

2. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including antiCTLA-4, and anti PD-L1 therapeutic antibodies

3. Treatment with another investigational agent or participation in another clinical trial within the last 28 days prior to initiating protocol therapy.

4. Subjects who have had chemotherapy or radiotherapy within 4 weeks prior to study treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks prior to initiating protocol therapy.

5. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of protocol therapy Subjects receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.

6. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of protocol therapy.

7. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti TNF-agents) within 2 weeks prior to initiation

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Oncoceutics, Inc.

INDUSTRY

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Victoria Bae-Jump, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UNC-Chapel Hill

Locations

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

De'Andrea Taylor

Role: CONTACT

deandrea_taylor@med.unc.edu

919-966-1195

Facility Contacts

Melisa Ramirez-Pineda

Role: primary

Melisa_Ramirez-Pineda@med.unc.edu

919-966-5996

Related Links

http://unclineberger.org/patientcare/clinical-trials/clinical-trials

University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Other Identifiers

5R21CA267584

Identifier Type: NIH

Identifier Source: secondary_id

View Link

LCCC2036

Identifier Type: -

Identifier Source: org_study_id