IMGN853 + Pembrolizumab for Endometrial Cancer

Recruiting at 2 trial locations

Overseen By DFCI Clinical Trials Hotline

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Folate supplements, Immunosuppressants

Disqualifiers: CNS metastases, Uncontrolled illness, Active infection, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 6 months

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying a drug combination as a possible treatment for endometrial cancer. The drugs involved in this study are: * mirvetuximab soravtansine (IMGN853) * pembrolizumab

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have had chemotherapy within 5 half-lives or 4 weeks before starting the study, and you cannot be on any investigational drugs. Hormonal therapy is allowed without a washout period.

What data supports the effectiveness of the drug combination IMGN853 and Pembrolizumab for endometrial cancer?

Pembrolizumab (Keytruda) has been shown to be effective in treating advanced endometrial cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), as it helps the immune system attack cancer cells. This effectiveness is supported by the KEYNOTE-158 trial, which demonstrated a meaningful response in patients with these types of endometrial cancer. ^{1 2 3 4 5}

Is the combination of IMGN853 and Pembrolizumab safe for treating endometrial cancer?

Pembrolizumab (Keytruda) has been shown to have a favorable safety profile in patients with advanced endometrial cancer, with common side effects including fatigue, itching, fever, and decreased appetite. Serious side effects like pneumonitis (lung inflammation) are rare, occurring in 1%-5% of patients. ^{1 3 5 6 7}

How is the drug combination of IMGN853 and Pembrolizumab unique for treating endometrial cancer?

The combination of IMGN853 and Pembrolizumab is unique because it pairs an antibody-drug conjugate (IMGN853) with an immune checkpoint inhibitor (Pembrolizumab), potentially enhancing the immune system's ability to target and destroy cancer cells in endometrial cancer, especially in cases with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). ^{1 3 4 6 8}

Research Team

Rebecca Porter, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with advanced or recurrent serous endometrial cancer that's microsatellite stable and FRα positive. Participants must have had 1-3 prior chemotherapy treatments but not certain other drugs, and should be in good health with no serious infections or autoimmune diseases. Women must use birth control and can't be pregnant.

Inclusion Criteria

My cancer is a type of advanced or recurrent serous endometrial cancer.

I have had 1 to 3 chemotherapy treatments for endometrial cancer.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Pregnant or nursing women

My doctor considers any other cancer I've had as cured.

I haven't taken immunosuppressive drugs in the last week, with some exceptions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mirvetuximab soravtansine and pembrolizumab intravenously every 3 weeks

6 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• IMGN853
• Pembrolizumab

Trial Overview The study tests a combination of two drugs, mirvetuximab soravtansine (IMGN853) and pembrolizumab, as a treatment for endometrial cancer. It aims to see how well these drugs work together in patients who meet specific criteria.

Participant Groups

Group I: IMGN853 + Pembrolizumab Experimental Treatment 2 Interventions

* Pembrolizumab is administered intravenously once every 3 weeks * IMGN853 is administered intravenously once every 3 weeks

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

ImmunoGen, Inc.

Industry Sponsor

Trials

33

Recruited

4,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

In a study of 44 women with advanced or recurrent MMRd/MSI-H endometrial adenocarcinomas treated with pembrolizumab, obesity (BMI≥30) was linked to a higher disease control rate (85.2%) compared to those with a BMI<30 (59.8%).

Patients with obesity also experienced significantly longer progression-free survival (PFS) while overall survival (OS) rates remained similar regardless of BMI, suggesting that body weight may influence treatment outcomes with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab. Bernard, L., How, JA., Patel, S., 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]

In the KEYNOTE-158 study, pembrolizumab showed a clinically meaningful objective response rate in patients with advanced MSI-H/dMMR endometrial cancer, with 84 out of 90 patients completing health-related quality of life (HRQoL) assessments.

Patients receiving pembrolizumab experienced significant improvements in their quality of life, with mean scores on the QLQ-C30 and EQ-5D-3L questionnaires increasing notably, especially among those who achieved a complete or partial response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study. O'Malley, DM., Bariani, GM., Cassier, PA., et al.[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]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In the KEYNOTE-158 study, pembrolizumab showed a 48% objective response rate in patients with advanced MSI-H/dMMR endometrial cancer, indicating significant antitumor activity.

The treatment was associated with manageable safety, with 76% of patients experiencing treatment-related adverse events, but no fatal events reported, highlighting its potential as a viable option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study. O'Malley, DM., Bariani, GM., Cassier, PA., et al.[2023]

References

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

New Approved Use for Keytruda. [2022]

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

Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab. [2023]

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

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

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

Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study. [2022]

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

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

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

Safety and Antitumor Activity of Pembrolizumab in Advanced Programmed Death Ligand 1-Positive Endometrial Cancer: Results From the KEYNOTE-028 Study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study. [2023]