ONC201 and Atezolizumab in Obesity-Driven Endometrial Cancer

NCT05542407 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: LCCC20365R21CA267584
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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

Keywords

Atezolizumab; ONC201; obesity

Outcome Measures

Primary Outcomes (1)

• Recommended phase 2 dose (RP2D)

  The RP2D will be determined based on the incidence of dose-limiting toxicities (DLT)s. A DLT is defined as all grade 3 or above toxicities that are related to study treatment and occur within the first cycle of therapy. Adverse events are assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE). A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate Instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

  Up to 3 weeks

Secondary Outcomes (3)

• Overall Response Rate (ORR)

  Up to 2 years

• Progression Free Survival (PFS)

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

Study Arms (2)

Obese

EXPERIMENTAL

Subjects with BMI \> 30 kg/m2

Drug: Atezolizumab; Drug: ONC201

Non-Obese

EXPERIMENTAL

Subjects with BMI ≤ 29.9 kg/m2

Drug: Atezolizumab; Drug: ONC201

Interventions

Atezolizumab DRUG

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

Non-Obese; Obese

ONC201 DRUG

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

Non-Obese; Obese

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0, 1, or 2
• Histologically confirmed metastatic or recurrent EC (endometrioid, carcinosarcoma, serous, clear cell, adeno-squamous and mixed histologies).
• 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
• 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.
• Life expectancy of at least 3 months.
• Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 72 hours prior to initiating study treatment.

You may not qualify if:

• Prior treatment with ONC201.
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including antiCTLA-4, and anti PD-L1 therapeutic antibodies
• Treatment with another investigational agent or participation in another clinical trial within the last 28 days prior to initiating protocol therapy.
• 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.
• 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.
• 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.
• 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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Genentech, Inc.: collaborator
• Oncoceutics, Inc.: collaborator
• National Cancer Institute (NCI): collaborator
• Jazz Pharmaceuticals: collaborator

Study Sites (1)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Endometrial Neoplasms; Neoplasm Metastasis; Carcinosarcoma; Disease; Obesity

Interventions

atezolizumab; TIC10 compound

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms

Study Officials

• Victoria Bae-Jump, MD, PhD

  UNC-Chapel Hill

  PRINCIPAL INVESTIGATOR

Central Study Contacts

De'Andrea Taylor

CONTACT

919-966-1195; deandrea_taylor@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2022
• First Posted: September 15, 2022
• Study Start: October 23, 2023
• Primary Completion (Estimated): February 21, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)