Targeted Therapy + Atezolizumab for Endometrial Cancer

(EndoMAP Trial)

Recruiting at 21 trial locations

Overseen By Quality Management and Compliance

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests drugs that target cancer cells, sometimes combined with an immune-boosting drug called atezolizumab. It focuses on patients with endometrial cancer that has returned or is persistent. The drugs are chosen based on the genetic profile of the patient's tumor to improve effectiveness.

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.

What data supports the effectiveness of the drug Trastuzumab emtansine (T-DM1) for treating endometrial cancer?

Trastuzumab emtansine (T-DM1) has shown effectiveness in treating HER2-positive metastatic breast cancer, suggesting potential benefits for other HER2-positive cancers, though specific data for endometrial cancer is not provided. ^{1 2 3 4 5}

What makes the Targeted Therapy + Atezolizumab treatment unique for endometrial cancer?

This treatment is unique because it combines multiple targeted therapies and immunotherapy drugs, like Atezolizumab and Trastuzumab emtansine, which aim to attack cancer cells in different ways, potentially offering a more comprehensive approach compared to standard treatments that often focus on a single mechanism. ^{6 7 8 9 10}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Atezolizumab (PD-L1 Inhibitor)
• Bevacizumab (VEGF Inhibitor)
• Inavolisib (PI3K Inhibitor)
• Ipatasertib (AKT Inhibitor)
• Letrozole (Aromatase Inhibitor)
• Talazoparib (PARP Inhibitor)
• Tiragolumab (TIGIT Inhibitor)
• Trastuzumab emtansine (HER2 Inhibitor)

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.

Participant Groups

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 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 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 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 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.

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

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

1. United States 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Ado-trastuzumab emtansine associated spider telangiectasia. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pneumonitis associated with Trastuzumab emtansine in a patient with metastatic breast cancer. [2022]

4. England 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). [2023]

5. England pubmed.ncbi.nlm.nih.gov

Application of trastuzumab emtansine in HER-2-positive and KRAS/BRAF-mutated colon cancer cells. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

Tislelizumab Combined with Carboplatin-Paclitaxel for Treatment of Metastatic or Recurrent Endometrial Cancer: a Retrospective Clinical Study. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Facts and Hopes in Immunotherapy of Endometrial Cancer. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea. [2022]