Targeted Therapy + Atezolizumab for Endometrial Cancer

(EndoMAP Trial)

Recruiting at 21 trial locations

Overseen By Quality Management and Compliance

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Alliance Foundation Trials, LLC.

Must not be taking: Immunostimulatory agents, Immunosuppressive medications

Disqualifiers: Other invasive malignancies, Autoimmune disease, Active tuberculosis, 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: 48 months

148 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to treat recurrent or persistent endometrial cancer using a combination of targeted therapy and atezolizumab, an immunotherapy drug. Researchers test different drug combinations to determine which are most effective and safe for those whose cancer has returned or resisted past treatments. Individuals whose endometrial cancer has returned after one or two previous treatments might qualify for this study. Participants must provide a tumor sample for specific tests to help determine the best treatment option. 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 innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive medications, you may need to stop them at least 2 weeks before starting the study, unless they are low-dose for specific conditions like asthma.

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

Previous studies have shown varying safety levels for the treatments tested in this trial.

Research has found that the combination of atezolizumab and bevacizumab exhibits strong anti-cancer effects with generally manageable side effects. Serious reactions were rare.

When combined with ipatasertib, atezolizumab is usually well-tolerated. Most studies have not reported severe unexpected side effects.

The combination of atezolizumab and trastuzumab emtansine has been tested for safety, showing it is reasonably safe, though some patients may experience typical cancer treatment side effects.

Atezolizumab with tiragolumab has a tolerable safety profile, with side effects similar to those of other cancer treatments.

Data indicate that inavolisib with letrozole has a manageable safety profile. Long-term studies have not found new safety concerns, suggesting it is well-tolerated.

Giredestrant with abemaciclib has been tested for safety. Some side effects occurred, but they were generally expected with these drugs.

Lastly, atezolizumab with talazoparib is FDA-approved for certain cancers, suggesting a known safety profile, although specific reactions can vary.

Overall, these treatments have shown they can be tolerated by patients, but individual reactions may differ. Participants should discuss potential risks with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for endometrial cancer because they offer a targeted approach that differs from current standards like surgery, radiation, and chemotherapy. Atezolizumab, an immunotherapy drug, works by enhancing the immune system's ability to detect and combat cancer cells, which is a promising shift from traditional treatments. The addition of targeted therapies like Bevacizumab, which inhibits blood vessel growth in tumors, and Trastuzumab emtansine (T-DM1), which delivers chemotherapy directly to cancer cells, provides a more precise attack on cancer while potentially reducing side effects. These unique features make these treatments stand out, offering hope for more effective and personalized cancer care.

What evidence suggests that this trial's treatments could be effective for endometrial cancer?

Research has shown that using atezolizumab with bevacizumab, one of the treatment arms in this trial, can significantly benefit patients with recurring endometrial cancer. One study found that this combination lowered the risk of death by 42% compared to other treatments. Another arm in this trial combines atezolizumab with ipatasertib, which studies suggest might extend the time patients live without their cancer worsening, especially if their tumors have certain genetic changes.

For the combination of atezolizumab and trastuzumab emtansine, another treatment arm in this trial, trastuzumab emtansine has been effective in treating HER2-positive breast cancer, suggesting it might also help with similar tumor types. When atezolizumab is used with tiragolumab, as in another arm of this trial, some patients experienced better response rates and longer periods without cancer progression.

Using inavolisib with letrozole, another treatment arm in this trial, has shown promise in helping patients with certain types of estrogen receptor-positive (ER+) cancers live longer without their cancer worsening. Finally, combining atezolizumab with talazoparib, also part of this trial, has shown mixed results but may benefit patients with specific genetic profiles of endometrial cancer. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with recurrent or persistent endometrial cancer who have undergone no more than two prior treatments (excluding certain hormonal therapies and radiosensitizers). Participants must have a life expectancy over 12 weeks, measurable disease per RECIST 1.1, and a suitable tumor specimen for biomarker testing. Those with autoimmune diseases, severe infections recently, significant cardiovascular disease, other recent malignancies except certain skin cancers and localized breast cancer treated over 5 years ago are excluded.

Inclusion Criteria

You are expected to live for at least 12 more weeks.

Measurable disease per RECIST 1.1

My endometrial cancer has returned or worsened after 1 or 2 treatments.

Exclusion Criteria

I have not received a live vaccine in the last 4 weeks and do not plan to during the study.

I have not had severe infections in the last 4 weeks.

I haven't taken strong immune-weakening medicines in the last 2 weeks, except for my asthma or low blood pressure.

Timeline for a Trial Participant

Pre-screening

Participants are pre-screened within 60 days of treatment assignment to have a tumor tissue sample submitted for next-generation sequencing (NGS) using FoundationOne® companion diagnostic (CDx) testing.

8 weeks

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment based on their cohort assignment, which may include targeted agents with or without atezolizumab.

48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival assessments.

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab
• Inavolisib
• Ipatasertib
• Letrozole
• Talazoparib
• Tiragolumab
• Trastuzumab emtansine

Trial Overview The study evaluates the effectiveness of targeted agents like Abemaciclib, Giredestrant, Talazoparib among others in combination with or without Atezolizumab—an immune checkpoint therapy—in treating endometrial cancer. It's designed to match participants to treatment based on specific biomarkers identified through genomic screening.

How Is the Trial Designed?

Group I: Inavolisib and Letrozole Cohort Experimental Treatment 2 Interventions

Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with tumors that with PIK3CA activating mutations in the absence of PTEN loss-of-function alterations or AKT1 activating mutations will be assigned to this cohort. Twenty-four participants will be enrolled. Once twenty-four participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.

Group II: Giredestrant and Abemaciclib Experimental Treatment 2 Interventions

Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with tumors that are RB1 intact with a local grade 1-2 estrogne receptor positive (ER+) are assigned to this cohort. Twenty-four participants will be enrolled. Once twenty-four participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.

Group III: Atezolizumab and Trastuzumab emtansine (TDM-1) Cohort - Closed to Accrual Experimental Treatment 2 Interventions

Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with tumors that with an amplification of ERBB2/HER2 will be assigned to this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.

Group IV: Atezolizumab and Tiragolumab Cohort - Closed to Accrual Experimental Treatment 2 Interventions

Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with tumor type MSI-H and/or tTMB \>=10 mut/mb will be assigned to this cohort. Twenty participants will be enrolled initially. Once twenty participants are enrolled, the cohort may be expanded if a positive signal is shown. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.

Group V: Atezolizumab and Talazoparib Cohort Experimental Treatment 2 Interventions

Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with tumors that have a ≥16%genomic loss of heterozygosity (LOH) will be assigned to this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.

Group VI: Atezolizumab and Ipatasertib Cohort - Closed to Accrual Experimental Treatment 2 Interventions

Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with PIK3CA/AKT1/PTEN-altered tumors will be enrolled in this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.

Group VII: Atezolizumab and Bevacizumab Cohort - Closed to Accrual Experimental Treatment 2 Interventions

Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with no specified gene signatures will be enrolled in this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.

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?

Alliance Foundation Trials, LLC.

Lead Sponsor

Trials

25

Recruited

27,200+

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

Foundation Medicine

Industry Sponsor

Trials

37

Recruited

17,600+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

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]

Checkpoint inhibitors like pembrolizumab and dostarlimab have become important treatment options for endometrial carcinoma, particularly for tumors that are mismatch repair deficient or have a high mutational load.

The review highlights the need for personalized immunotherapy approaches based on the distinct molecular subtypes of endometrial cancer, as these subtypes exhibit different characteristics that could influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facts and Hopes in Immunotherapy of Endometrial Cancer. Marín-Jiménez, JA., García-Mulero, S., Matías-Guiu, X., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, has been approved for treating relapsed MSI-H endometrial cancer after chemotherapy, showing promise in restoring anti-tumor immunity by blocking PD-1 interactions.

Despite encouraging response rates in MSI-H patients, over 50% do not respond to pembrolizumab, highlighting the need for better understanding of MSI status and identifying specific patient populations that may benefit from treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma. Turinetto, M., Lombardo, V., Pisano, C., et al.[2022]

Ado-trastuzumab emtansine (T-DM1) is generally safe and effective for treating HER2-positive breast cancer, leading to a complete response in metastases, although it can cause side effects like fatigue and diarrhea.

In a case study, a patient developed telangiectasia (spider veins) after 9 months of T-DM1 treatment, suggesting that while skin toxicity is rare, it may occur due to vascular changes caused by the drug, warranting careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ado-trastuzumab emtansine associated spider telangiectasia. Gursoy, P., Acar, A., Acikalin, T.[2022]

Trastuzumab emtansine (TDM-1) is effective for treating advanced breast cancer but can cause rare pulmonary complications, such as drug-induced pneumonia, as seen in a case study of a 47-year-old female patient.

In this case, the patient responded well to systemic corticosteroids after being diagnosed with drug-induced pneumonia, highlighting the importance of ruling out infections and metastasis before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pneumonitis associated with Trastuzumab emtansine in a patient with metastatic breast cancer. Uğraklı, M., Araz, M., Demirkıran, A., et al.[2022]

Trastuzumab emtansine (T-DM1) demonstrated superior inhibitory effects on HER-2-positive colon cancer cells with KRAS/BRAF mutations compared to other treatments like cetuximab and trastuzumab, suggesting its potential as an effective therapy for this challenging cancer type.

The combination of T-DM1 with metformin enhanced the drug's efficacy by increasing caveolin-1 expression, which improved T-DM1 uptake and led to significant tumor growth inhibition in a xenograft mouse model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of trastuzumab emtansine in HER-2-positive and KRAS/BRAF-mutated colon cancer cells. Chung, YC., Chiu, HH., Wei, WC., et al.[2020]

HER2 overexpression and/or amplification is common in uterine serous carcinomas, making HER2 a promising target for therapy in endometrial carcinoma.

Trastuzumab, an antibody targeting HER2, has shown clinical responses in case reports, and ongoing clinical trials are evaluating its efficacy, highlighting the need for standardized HER2 testing criteria to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges. Buza, N., Roque, DM., Santin, AD.[2022]

In a study of 110 patients with HER2-positive metastatic breast cancer who had previously received multiple treatments, the antibody-drug conjugate trastuzumab emtansine (T-DM1) showed an overall response rate of 34.5% and a clinical benefit rate of 48.2%, indicating its effectiveness as a treatment option.

T-DM1 was well tolerated, with most side effects being mild (grades 1 to 2), and the most common severe side effects included thrombocytopenia and fatigue, suggesting a favorable safety profile for patients who have exhausted other HER2-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. Krop, IE., LoRusso, P., Miller, KD., et al.[2022]

In a study of 128 female patients with HER2-positive metastatic breast cancer who previously received trastuzumab emtansine (T-DM1), the median progression-free survival (rwPFS) was 5.7 months, indicating some effectiveness of post-T-DM1 therapies.

Patients who continued anti-HER2 therapy after T-DM1 had a better median rwPFS of 6.3 months compared to 4.8 months for those who did not, suggesting that ongoing anti-HER2 treatment may provide additional benefits, although overall effectiveness remains limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of post-trastuzumab emtansine treatment in patients with HER2-positive, unresectable and/or metastatic breast cancer: a retrospective observational study (KBCSG-TR 1917). Nakayama, T., Yoshinami, T., Yasojima, H., et al.[2023]

In a study of 48 patients with recurrent endometrial cancer treated with pembrolizumab and lenvatinib, the best objective response rate was 23.8%, indicating a lower effectiveness compared to clinical trial results.

The treatment was associated with notable side effects, with 56.2% of patients requiring a dose reduction of lenvatinib and 16.7% discontinuing treatment due to adverse events, highlighting the importance of monitoring for safety in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea. Kim, J., Noh, JJ., Lee, TK., et al.[2022]

Citations

1. cancernetwork.com cancernetwork.com/view/long-lasting-benefit-observed-with-atezolizumab-and-bevacizumab-in-recurrent-endometrial-cancer

Long-Lasting Benefit Observed With Atezolizumab and ... Results from a phase 2 trial indicated that atezolizumab and bevacizumab yielded a significant duration of response in recurrent endometrial cancer.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8165028/

Bevacizumab in Advanced Endometrial Cancer - PMC Prospective data have demonstrated the efficacy of bevacizumab monotherapy in the treatment of advanced endometrial cancer. Bevacizumab is used off-label, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03526432

NCT03526432 | Phase II Study of Atezolizumab + ... This phase 2 study using atezolizumab and bevacizumab aims to study the objective tumor response in women with recurrent endometrial cancer. Drugs will be ...

4. roche.com roche.com/media/releases/med-cor-2017-06-03

Roche presents new data for TECENTRIQ® (atezolizumab) ... Specifically, TECENTRIQ plus Avastin resulted in an Overall Response Rate (ORR) of 26% in all-crossover patients (28% in crossover post- ...

5. oncpracticemanagement.com oncpracticemanagement.com/issues/2020/may-2020-vol-10-no-5/atezolizumab-bevacizumab-combo-improves-survival-and-quality-of-life-in-unresectable-liver-cancer

Atezolizumab-Bevacizumab Combo Improves Survival and ... Data from the IMbrave150 trial showed a 42% reduction in mortality risk with atezolizumab plus bevacizumab versus sorafenib monotherapy. In addition, the median ...

6. tecentriq-hcp.com tecentriq-hcp.com/content/dam/gene/tecentriq-hcp/hcc/pdfs/tecentriq-avastin-hcc-summary.pdf

TECENTRIQ + Avastin Efficacy and Safety Summary Select Important Safety Information. Serious and sometimes fatal adverse reactions occurred with TECENTRIQ treatment. Warnings and precautions include ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/125085s337lbl.pdf

avastin - accessdata.fda.gov The safety data in Warnings and Precautions and described below reflect exposure to Avastin in 4463 patients including those with mCRC (AVF2107g, E3200), non- ...