IMGN853 + Pembrolizumab for Endometrial Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new drug combination to treat advanced or recurring endometrial cancer, with a focus on serous endometrial cancer. The treatment involves two drugs, mirvetuximab soravtansine (IMGN853, an experimental treatment) and pembrolizumab, administered through IV every three weeks. Suitable candidates have endometrial cancer treated with up to three rounds of chemotherapy and tumors that are microsatellite stable and FRα positive. Participants should not have received certain prior treatments or have severe health conditions, such as uncontrolled heart disease or active infections. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

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.

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

Research shows that the combination of mirvetuximab soravtansine (IMGN853) and pembrolizumab is being explored as a potential treatment for endometrial cancer. Previous studies have found that this combination is generally well-tolerated, meaning most patients can handle it without major problems. The safety data from these studies did not reveal any unexpected side effects.

Mirvetuximab soravtansine has been tested in other trials and was found to be manageable for most patients. Pembrolizumab, already approved for treating other types of cancer, has a known safety profile. Common side effects of pembrolizumab include tiredness and mild skin rash, which are usually manageable.

Overall, the safety data suggest that patients can handle the treatment without severe issues. However, like any treatment, there may be risks, and patients should consult their doctor about what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for endometrial cancer?

Researchers are excited about the combination of IMGN853 and Pembrolizumab for endometrial cancer because it offers a novel approach compared to current treatments. Unlike standard therapies that typically focus on hormone manipulation or chemotherapy, IMGN853 is an antibody-drug conjugate that delivers a potent anti-cancer agent directly to tumor cells, increasing precision and minimizing damage to healthy cells. Pembrolizumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. Together, these treatments provide a dual mechanism of action—targeted delivery and immune system activation—that could potentially enhance effectiveness and reduce side effects compared to traditional options.

What evidence suggests that this drug combination could be an effective treatment for endometrial cancer?

Research has shown that combining mirvetuximab soravtansine (IMGN853) and pembrolizumab may effectively treat endometrial cancer. This trial will specifically evaluate this combination for patients with FRalpha-positive, pMMR/MSS serous cancer. Early studies suggest that this drug pair can slow tumor growth. Mirvetuximab soravtansine attaches to cancer cells, while pembrolizumab helps the immune system attack them. Overall, the initial results are promising and indicate that this combination could be a helpful treatment option. ^{1 2 4 6 7}

Who Is on the Research Team?

Rebecca Porter, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03835819

A Phase 2 Study of Mirvetuximab Soravtansine (IMGN853) ... This research study is studying a drug combination as a possible treatment for endometrial cancer. The drugs involved in this study are: mirvetuximab ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10093320/

Immune Environment and Immunotherapy in Endometrial ... We report recent and current immunotherapy-based clinical trials and provide a review of emerging data that are likely to impact immunotherapy development.

3. asco.org asco.org/abstracts-presentations/ABSTRACT341407

A phase 2, two-stage study of mirvetuximab soravtansine ... A phase 2, two-stage study of mirvetuximab soravtansine (IMGN853) in combination with pembrolizumab in patients with microsatellite stable (MSS) endometrial ...

4. dana-farber.org dana-farber.org/clinical-trials/18-602

A Phase 2, two-stage, study of mirvetuximab soravtansine ... This research study is studying a drug combination as a possible treatment for endometrial cancer ... (IMGN853) - pembrolizumab.

5. onclive.com onclive.com/view/mirvetuximab-soravtansine-plus-pembrolizumab-makes-a-splash-in-pmmr-mss-fralpha-endometrial-cancer

Mirvetuximab Soravtansine Plus Pembrolizumab Makes a ... Mirvetuximab soravtansine plus pembrolizumab displays efficacy in recurrent or persistent, FRalpha-positive, pMMR/MSS serous endometrial cancer.

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/19/NCT03835819/Prot_SAP_000.pdf

A Phase 2, two-stage, study of mirvetuximab soravtansine ( ... Review of preliminary safety data from Study 0402 (combination therapy), did not indicate any ... 5.3.2 Pembrolizumab (MK-3475). Dosing. Page 25 ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03835819/

Clinical Trial: NCT03835819 Description: This research study is studying a drug combination as a possible treatment for endometrial cancer. The drugs involved in this study ...