Futibatinib + Pembrolizumab for Endometrial Cancer

Overseen By Siqing fu

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antiepileptics, Steroids, Immunosuppressives, others

Disqualifiers: Heart failure, Stroke, Autoimmune, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you should not be on certain investigational drugs, live vaccines, or strong inhibitors and inducers of CYP3A4 within specific timeframes before starting the study drugs. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drugs Futibatinib and Pembrolizumab for treating endometrial cancer?

Pembrolizumab has shown effectiveness in treating advanced endometrial cancer, especially in patients with specific genetic features like microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors. It has been approved for use in these cases, indicating its potential benefit in treating endometrial cancer. ^{1 2 3 4 5}

What safety information is available for pembrolizumab in endometrial cancer treatment?

Pembrolizumab, when used with lenvatinib for endometrial cancer, has shown a safety profile consistent with each drug used alone. Common side effects include high blood pressure, low thyroid function, diarrhea, nausea, vomiting, loss of appetite, tiredness, and weight loss. ^{1 2 3 4 6}

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

The combination of Futibatinib and Pembrolizumab is unique because it pairs a targeted therapy (Futibatinib) with an immunotherapy (Pembrolizumab), potentially offering a novel approach for endometrial cancer treatment. Pembrolizumab is already used for certain types of endometrial cancer, but combining it with Futibatinib could enhance its effectiveness by targeting different pathways in the cancer cells. ^{1 2 3 4 5}

What is the purpose of this trial?

It's propose this pilot phase 2 study to explore the combination therapy of futibatinib with pembrolizumab in patients with metastatic microsatellite stable (MSS) endometrial carcinoma to provide a well-tolerated regimen for durable responses.

Research Team

Siqing fu

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced or metastatic endometrial carcinoma that's microsatellite stable (MSS) and can't be cured by surgery or radiation. They should have tried or declined chemotherapy, have good organ function, no prior anti-PD-(L)1 therapy or FGFR inhibitors, measurable disease per RECIST 1.1 criteria, and not be pregnant while on the trial.

Inclusion Criteria

Serum calcium ≤ ULN

I am fully active or can carry out light work.

My kidney function, measured by creatinine levels or clearance, is within the required range.

Exclusion Criteria

Lactation or pregnancy

I currently have active bleeding or an active stomach ulcer.

I have another cancer that needs treatment besides hormone therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination therapy of futibatinib and pembrolizumab

12 weeks

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Futibatinib
• Pembrolizumab

Trial Overview The study tests a combination of futibatinib and pembrolizumab in patients with MSS endometrial carcinoma to find a treatment that's well-tolerated and provides lasting responses. It's a phase II pilot study designed to assess this new regimen.

Participant Groups

Group I: pembrolizumab Experimental Treatment 1 Intervention

Group II: futibatini Experimental Treatment 1 Intervention

Futibatinib is already approved in United States for the following indications:

Approved in United States as Lytgobi for:

• Treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Comprehensive Cancer Network

Collaborator

Trials

121

Recruited

7,400+

Findings from Research

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]

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]

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 (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]

The combination of lenvatinib and pembrolizumab shows significant clinical benefits for patients with endometrial carcinoma, with a safety profile consistent with each drug's individual use, primarily involving manageable side effects like hypertension and hypothyroidism.

Effective management of lenvatinib's common adverse events is crucial to maximize its efficacy, as most side effects can be prevented or mitigated through proactive monitoring and intervention during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. Lorusso, D., Danesi, R., Locati, LD., et al.[2023]

References

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

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

2. 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]

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

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

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

New Approved Use for Keytruda. [2022]

5. 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]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023]