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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, futibatinib (a new potential drug) and pembrolizumab, to determine their effectiveness in treating endometrial cancer that has spread and does not respond to standard surgery or radiation. Researchers aim to find a treatment that provides lasting benefits without severe side effects. Suitable participants have been diagnosed with metastatic microsatellite stable endometrial cancer and have tried at least one form of chemotherapy without success. This trial offers an opportunity to try a new treatment that could improve outcomes for those with this specific type of cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Previous studies have shown that futibatinib has a manageable safety profile, even across different tumor types. Most side effects were temporary and treatable. This indicates that while some side effects may occur, they are often short-lived and controllable.

Research on pembrolizumab in various cancers, including endometrial cancer, has shown that its safety remains consistent over time, with no new safety issues arising in recent years.

These findings suggest that the combination of futibatinib and pembrolizumab is likely well-tolerated. However, like any treatment, side effects can occur, but they are generally manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Futibatinib and Pembrolizumab for endometrial cancer because they offer new ways to target the disease. Unlike traditional chemotherapy, which attacks cancer cells and healthy cells alike, Pembrolizumab is an immunotherapy that boosts the body's immune system to better recognize and fight cancer cells. Futibatinib is a newer option that targets specific mutations within cancer cells, potentially leading to more precise treatment and fewer side effects. Together, these drugs may provide a more targeted and effective approach to treating endometrial cancer, offering hope for improved outcomes.

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

Research has shown that futibatinib, one of the treatments in this trial, has potential in treating endometrial cancer. Studies found that about 13.7% to 14.3% of patients experienced tumor shrinkage, indicating a small percentage saw their tumors get smaller. Additionally, patients treated with futibatinib had stable cancer for about 5.6 months on average, meaning the cancer did not worsen during this time.

Pembrolizumab, another treatment option in this trial, has shown better results. In clinical trials, it helped shrink tumors in about 46% of adults with certain advanced endometrial cancers. Patients taking pembrolizumab also experienced a longer period before their cancer worsened, averaging 13.1 months compared to 8.7 months for those not taking the drug. These findings suggest that using futibatinib together with pembrolizumab might offer a new treatment option for people with metastatic microsatellite stable (MSS) endometrial cancer. ^{4 6 7 8 9}

Who Is on the Research Team?

Siqing fu

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12215578/

Drug discovery in advanced and recurrent endometrial cancer The study reported an ORR of 14.3% (95% CI 8.8–21.4), with a median PFS of 5.6 months (95% CI 3.7–6.3) and a median OS of 10.6 months (95% CI 8.9–14.9) [70].

2. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/futibatinib-otsuka-pharmaceutical-endometrial-cancer-likelihood-of-approval/

Futibatinib by Otsuka Pharmaceutical for Endometrial Cancer According to GlobalData, Phase II drugs for Endometrial Cancer have a 22% phase transition success rate (PTSR) indication benchmark for ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05036681

A Phase II Study of Futibatinib and Pembrolizumab in ... To evaluate the objective response rate (ORR) of futibatinib and pembrolizumab in patients with metastatic microsatellite stable (MSS) endometrial carcinoma.

4. researchgate.net researchgate.net/publication/384781567_Pharmacological_characteristics_and_clinical_effectiveness_of_Futibatinib_LytgobiR_Tablets_a_covalently-binding_irreversible_FGFR1-4_inhibitorgongyoujiehexingbukenideFGFR14zuhaiyaoFutibatinibritogobiR

Pharmacological characteristics and clinical effectiveness ... The overall response rate was 41.7%, showing consistent efficacy regardless of co-occurring genomic alterations. Although some typical FGFR ...

5. aacrjournals.org aacrjournals.org/cancerdiscovery/article/12/2/402/678504/Futibatinib-an-Irreversible-FGFR1-4-Inhibitor-in

Futibatinib, an Irreversible FGFR1–4 Inhibitor, in Patients with ... Futibatinib demonstrated an objective response rate (ORR) of 13.7%, with responses in a broad spectrum of tumors (cholangiocarcinoma and gastric, urothelial, ...

6. lytgobi.com lytgobi.com/hcp/efficacy-and-safety/safety-profile

Safety Profile & Adverse Reactions View safety profile and adverse reaction information for LYTGOBI reported in the FOENIX-CCA2 trial. Please see Important Safety Information and full ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11016890/

Safety Profile and Adverse Event Management for Futibatinib ... Futibatinib showed a consistent and manageable safety profile across patients with various tumor types. AECIs were mostly reversible with appropriate clinical ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12365427/

Safety profiles of the new target therapies—pemigatinib ... This systematic review aims to summarize the results obtained with three new targeted therapies—pemigatinib, futibatinib, and ivosidenib—for the ...

9. ccanewsonline.com ccanewsonline.com/issues/2020/october-2020-vol-1-no-2/futibatinib-safe-and-effective-in-patients-with-advanced-or-metastatic-intrahepatic-cholangiocarcinoma-and-fgfr2-fusions

Futibatinib Safe and Effective in Patients with Advanced or ... The first study analyzed efficacy and safety data, and the second study ... Endometrial Cancer, Esophageal Cancer, Family Medicine, Gastroenterology ...