NCT05542407 · UNC Lineberger Comprehensive Cancer Center
ONC201 and Atezolizumab in Obesity-Driven Endometrial Cancer
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
Atezolizumab
10 mg/kg- 20 mg/kg Atezolizumab will be administered by intravenous, on day 1 of each 21-day cycle.
DRUG
ONC201
375 mg once weekly - 625 mg ONC201 will be administered orally, once or twice weekly.
Primary outcome measures
Recommended phase 2 dose (RP2D)
Time frame: Up to 3 weeks
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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.
Exclusion criteria
- 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
Where
- Chapel Hill, North Carolina
Collaborators
Genentech, Inc., Oncoceutics, Inc., National Cancer Institute (NCI), Jazz Pharmaceuticals
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jan 29, 2026 · Source of record for eligibility and locations