ONC201 + Atezolizumab for Endometrial Cancer

Overseen By De'Andrea Taylor

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Antibiotics, Immunostimulants, Immunosuppressants, others

Disqualifiers: Prior ONC201, Immune checkpoint, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

58 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new treatment combination for endometrial cancer, which affects the lining of the uterus. Researchers are exploring how atezolizumab (an immunotherapy drug) and ONC201 work together to treat both obese and non-obese women with advanced or recurring endometrial cancer. Participants should have endometrial cancer that has progressed after at least one type of chemotherapy and should be able to measure their cancer accurately with scans. This study is crucial for finding better treatments for endometrial cancer, especially for those who haven't responded well to other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting. You must not have had chemotherapy or radiotherapy within 4 weeks, and you should not be on systemic immunosuppressive or immunostimulatory medications within 2 weeks before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies found atezolizumab safe for patients with endometrial cancer. Some patients experienced long-lasting benefits, with the treatment continuing to work well over time, making it a promising cancer treatment option.

ONC201 has also undergone testing. Research has shown it to be very safe, with trials indicating it is generally well-tolerated by patients.

These findings suggest that both atezolizumab and ONC201 are safe for human use based on past studies. However, since this trial is in its early phase, more research is needed to confirm their safety when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ONC201 combined with Atezolizumab for endometrial cancer because of their unique mechanisms. ONC201 is a first-in-class imipridone that targets the dopamine receptor D2 (DRD2) and ClpP, which might lead to cancer cell death in a new way compared to traditional chemotherapy. Atezolizumab, on the other hand, is an immunotherapy that helps the body’s immune system recognize and attack cancer cells by blocking the PD-L1 protein. This combination aims to tackle cancer from two different angles: disrupting cancer cell survival pathways and boosting the immune response to fight the cancer more effectively.

What evidence suggests that the combination of atezolizumab and ONC201 could be effective for endometrial cancer?

Research has shown that ONC201, one of the treatments in this trial, can slow the growth of endometrial cancer cells by stopping them from dividing. It effectively reduces the number of these cancer cells even at low doses. Studies have found that atezolizumab, another treatment option in this trial, helps patients with advanced or returning endometrial cancer live longer without the cancer worsening. Although few patients responded to the treatment, some experienced long-lasting benefits. This trial will explore the potential of using these two treatments together to enhance their effectiveness, especially for cancer that has returned or spread. ^{3 4 6 7 8}

Who Is on the Research Team?

Victoria Bae-Jump, MD, PhD

Principal Investigator

UNC-Chapel Hill

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced or recurrent endometrial cancer, who have measurable disease and have had progression after chemotherapy. They must understand the study and consent to participate. Those with adequate organ function and a life expectancy of at least 3 months can join. People cannot join if they've had certain recent treatments, including ONC201, other clinical trials, chemotherapy, radiotherapy, immunostimulatory agents, systemic immunosuppressive medications or checkpoint blockade therapies.

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.

Life expectancy of at least 3 months.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I haven't taken any immune-weakening medications in the last 2 weeks.

I have previously been treated with specific immune therapies.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of atezolizumab and ONC201 based on body weight to treat endometrial cancer

3 weeks

Weekly visits for dose-limiting toxicity assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• ONC201

Trial Overview The trial tests the safety of combining Atezolizumab and ONC201 in treating obesity-related endometrial cancer based on body weight. This combination isn't FDA-approved yet for this use. The study includes both obese and non-obese subjects with metastatic/recurrent endometrial cancer to see how well these drugs work together.

How Is the Trial Designed?

Group I: Obese Experimental Treatment 2 Interventions

Subjects with BMI \> 30 kg/m2

Group II: Non-Obese Experimental Treatment 2 Interventions

Subjects with BMI ≤ 29.9 kg/m2

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Oncoceutics, Inc.

Industry Sponsor

Trials

10

Recruited

500+

Published Research Related to This Trial

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

In a study of 24 patients with metastatic or recurrent endometrial cancer, the combination of tislelizumab with carboplatin-paclitaxel showed a promising objective response rate of 62.5%, indicating effective treatment for this challenging condition.

The treatment was found to be safe, with no allergic reactions or treatment-related deaths reported, although half of the patients experienced moderate to severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab Combined with Carboplatin-Paclitaxel for Treatment of Metastatic or Recurrent Endometrial Cancer: a Retrospective Clinical Study. Gao, FF., Zhang, XL., Chen, JL., et al.[2022]

In the phase III IMagyn050 trial involving patients with newly diagnosed ovarian cancer, the addition of atezolizumab to standard chemotherapy did not improve progression-free survival (PFS) in patients with BRCA1/2 mutations or homologous recombination deficiency (HRD).

Despite the presence of BRCA1/2 mutations or HRD, most ovarian tumors exhibited low tumor mutation burden (TMB), indicating that genomic instability does not predict enhanced sensitivity to immune checkpoint inhibitors like atezolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. Landen, CN., Molinero, L., Hamidi, H., et al.[2023]

Atezolizumab, a monoclonal antibody targeting PD-L1, has shown significant improvements in progression-free and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) when combined with chemotherapy, as demonstrated in the IMpower studies.

The safety profile of atezolizumab in combination with chemotherapy is acceptable, with common immune-related adverse events including rash (18-28%), hypothyroidism (8-15%), and hepatitis (5-17%), consistent with its known effects as a single agent, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. Manzo, A., Carillio, G., Montanino, A., et al.[2022]

In a phase Ib study involving 20 patients with platinum-resistant ovarian cancer, the combination of atezolizumab and bevacizumab demonstrated a safety profile consistent with the individual drugs, with 95% experiencing treatment-related adverse events, but no grade 5 events reported.

The treatment resulted in a 15% overall response rate, with some patients achieving durable responses lasting up to 18.9 months, and a disease control rate of 55%, indicating potential efficacy in managing this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of Atezolizumab Plus Bevacizumab in Patients with Ovarian Cancer: A Phase Ib Study. Moroney, JW., Powderly, J., Lieu, CH., et al.[2021]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

The combination of temsirolimus and topotecan was found to be tolerable in women with advanced gynecologic cancers who had not received prior pelvic radiotherapy, with 15 patients participating in the study and a total of 43 treatment cycles administered.

However, the treatment caused dose-limiting toxicities, specifically myelosuppression (neutropenia and thrombocytopenia), indicating that while the regimen may be safe for some patients, it cannot be given at full doses in combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of weekly temsirolimus and topotecan in the treatment of advanced and/or recurrent gynecologic malignancies. Temkin, SM., Yamada, SD., Fleming, GF.[2022]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

In a long-term follow-up of patients with metastatic urothelial carcinoma (mUC) who had previously undergone platinum-based chemotherapy, atezolizumab showed a 24-month overall survival (OS) rate of 23%, compared to 13% for those receiving chemotherapy, indicating a potential for durable remission.

Patients treated with atezolizumab experienced fewer severe treatment-related adverse events (43% for chemotherapy vs. 22% for atezolizumab), suggesting a better safety profile, although atezolizumab was associated with more mild adverse events of special interest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab Versus Chemotherapy in Patients with Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: A Long-term Overall Survival and Safety Update from the Phase 3 IMvigor211 Clinical Trial. van der Heijden, MS., Loriot, Y., Durán, I., et al.[2022]

Citations

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Atezolizumab Plus Chemo Improves PFS in Frontline, ... Twelve-month OS rates were 80.1%, compared with 74.9%, with atezolizumab and placebo, respectively, while 24-month OS rates were 62.2% vs 58.0%.

2. curetoday.com curetoday.com/view/tecentriq-plus-chemo-shows-comparable-survival-in-endometrial-cancer

Tecentriq Plus Chemo Shows Comparable Survival in ... Adding Tecentriq (atezolizumab) to chemotherapy resulted in survival outcomes comparable to placebo plus chemotherapy in patients with advanced ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204524003346

Atezolizumab and chemotherapy for advanced or recurrent ... Atezolizumab plus chemotherapy increased progression-free survival in patients with advanced or recurrent endometrial carcinoma, particularly in those with dMMR ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03603184

NCT03603184 | Atezolizumab Trial in Endometrial Cancer Regarding efficacy ORR was 13% [2/15] by RECIST. Atezolizumab seemed to have a favorable safety profile, with durable clinical benefit in some patients. ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38606824/

Cost-effectiveness of atezolizumab plus chemotherapy for ... This study assessed the cost-effectiveness of atezolizumab in combination with chemotherapy for patients with advanced or recurrent endometrial cancer (EC)

6. cancernetwork.com cancernetwork.com/view/atezolizumab-combo-displays-noninferior-survival-in-endometrial-cancer

Atezolizumab Combo Displays Noninferior Survival in ... A significant survival improvement was observed among patients with dMMR carcinomas who received atezolizumab/chemotherapy.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39102832/

a randomised, double-blind, placebo-controlled, phase 3 trial Median overall survival was 38·7 months (95% CI 30·6-NE) in the atezolizumab group and 30·2 months (25·0-37·2) in the placebo group (HR 0·82, 95 ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.15_suppl.5585

Clinical activity, safety and biomarker results from a phase ... Background: The prognosis for patients (pts) with rEC remains poor, with a 5-y OS of 20%-26%. We report safety, clinical activity and ...