A Phase II Study of Futibatinib and Pembrolizumab in Metastatic Microsatellite Stable Endometrial Carcinoma

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Cancer; Endometrial Carcinoma; Endometrium Cancer
• Intervention / Treatment: Drug: Futibatinib; Drug: Pembrolizumab

Detailed Description

Primary Objectives

• To evaluate the objective response rate (ORR) of futibatinib and pembrolizumab in patients with metastatic microsatellite stable (MSS) endometrial carcinoma.
• To evaluate the safety and tolerability.

Primary Endpoints

• Complete responses (CRs) and partial responses (PRs) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Adverse events (AEs: clinical manifestations and laboratory tests) and serious adverse events (SAEs) according to the NCI Common Terminology Criteria for Adverse Events [CTCAE] version 5.0.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

To be eligible for this trial, patients must meet all of the following eligibility criteria.

• Patients with histologically confirmed locally advanced or metastatic endometrial carcinoma that is not amenable to curative surgical- or radiation-based intervention, who have received or declined at least one-line systemic chemotherapy.
• Known microsatellite stable (MSS) as pre-identified in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory
• At least one measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Age ≥18 years.
• Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test prior to administration of the first dose of futibatinib within 7 days prior to initiation of therapy (C1D1), and must agree to use effective birth control initiated immediately following negative serum pregnancy test during screening period, during the study, and for at least 180 days after the last dose (or longer based on local requirements). Female patients are not considered to be of child-bearing potential if they are post-menopausal (no menses for 12 months without an alternative medical cause) or permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).

Adequate organ functions as defined below:

Absolute neutrophil count (ANC) ≥ 1,000 /μL. Hemoglobin (Hb) ≥ 9 g/dL. Platelets ≥ 75,000 /μL. Total bilirubin ≤ 1.5 x ULN (upper limit of normal); or total bilirubin < 3 x ULN with direct bilirubin ≤ ULN in patients with well documented Gilbert's Syndrome.

ALT ≤ 3 x ULN or ≤ 5 x ULN if liver metastases persist. Serum phosphate ≤ 1.5 x ULN. Serum calcium ≤ ULN. Serum albumin ≥ 3 g/dL. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCl) ≥ 40 mL/min by the Cockcroft-Gault method* or 24-hour urine collection.

*CrCl = (140-age) x (weight [kg]) x 0.85 / (72 x serum creatinine mg/dL)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• No prior treatment with anti-PD-(L)1 therapy and a FGFR inhibitor.
• Ability to read and fully understand the requirements of the trial, willingness to comply with all trial visits and assessments, and willingness and ability to sign an institutional review board (IRB)-approved written informed consent document.
• Any prior radiation must have been completed at least 14 days prior to the start of study drugs, and patients must have recovered from any acute adverse effects prior to the start of study treatment (Radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks).
• Ability to take oral medications without medical history of malabsorption or other chronic gastrointestinal disease, or other conditions that may hamper compliance and/or absorption of the study agents (feeding tube is not permitted).
• Provision of an archival tissue block, or 10 formalin-fixed paraffin-embedded (FFPE) slides obtained within 6 months prior to study entry; or agreeing to have biopsies if archival tissues are not available.

Exclusion Criteria:

• Patients who meet any of the following criteria will be not eligible for the study:
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure (New York Heart Association Class III or IV), history of myocardial infarction, unstable angina, stroke or transient ischemic attack within 6 months before study enrollment, history or current evidence of uncontrolled ventricular arrhythmia. Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death. Chronic diarrhea diseases considered to be clinically significant in the opinion of the Investigator. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or futibatinib and pembrolizumab administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study.
• History and/or current evidence of any of the following disorders: Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator; Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator; and Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant in the opinion of the Investigator and a trained ophthalmologist who performs the test.
• Having not recovered from a major surgical procedure or significant traumatic injury (i.e., still needing additional surgical or medical care for these issues): major surgical procedures ≤ 28 days of treatment entry, or minor surgical procedures ≤ 7 days. No waiting period required following port-a-cath or other central venous access placement.
• Unresolved clinically significant Grade 2 toxicity from prior therapy.
• Patient has an inability to swallow oral medications. Note: Patient may not have a percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN).
• Clinically active bleeding, or active gastric or duodenal ulcer.
• Fridericia's corrected QT interval (QTcF =QT/∛(60/HR) ) > 470 ms on ECG conducted during Screening. Patients with an atrioventricular pacemaker or other condition (for example, right bundle branch block) that renders the QT measurement invalid are an exception and the criterion does not apply.
• History of allergic reactions to the study drugs, or any component of the products.
• Currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study. If a patient is currently enrolled in a clinical trial involving non-approved use of a device, then agreement with the investigator and the sponsor is required to establish eligibility.
• Any treatment specifically for systemic tumor control given within 3 weeks before the initiation of the study drugs, within 2 weeks if cytotoxic agents were given weekly, within 6 weeks for nitrosoureas or mitomycin C, within 5 half-lives for targeted agents with half-lives and pharmacodynamic effects lasting < 5 days, or failure to recover from toxic effects of any therapy before the initiation of the study drugs. A drug that has not received regulatory approval for any indication within 14 or 21 days of treatment for a non-myelosuppressive or myelosuppressive agent, respectively.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: Bacille Calmette-Guérin vaccine, measles, mumps, rabies, rubella, typhoid vaccine, varicella/zoster, and yellow fever. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed.
• Received strong inhibitors and inducers and sensitive substrates of CYP3A4 within 2 weeks (see appendix A).
• Symptomatic primary tumors or metastasis in the brain and/or central nervous system that are uncontrolled with antiepileptics and require steroids at a dose of prednisone > 10 mg/day or equivalent.
• Evidence of leptomeningeal or lymphangitic carcinomatosis.
• A history of another primary malignancy that is currently clinically significant, requiring active intervention except for hormone therapy.
• Concurrent immunosuppressive therapy or steroid (> 10 mg/day prednisone or equivalent).
• Previously documented or suspected autoimmune disease requiring active immunosuppressive therapy (adequately treated skin rash or replacement therapy for endocrinopathies is not excluded), and history of or current pneumonitis.
• Lactation or pregnancy.
• Known human immunodeficiency virus requiring HAART treatment due to unknown drug-drug interactions or known active hepatitis B or C virus infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pembrolizumab	Drug: Pembrolizumab; Given by vein over about 30-60 minutes on Day 1 of all cycles
Experimental: futibatini	Drug: Futibatinib; tablets by mouth 1 time every day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To Evaluate the Objective Response Rate (ORR) of Futibatinib and Pembrolizumab in Patients With Metastatic Microsatellite Stable (MSS) Endometrial Carcinoma.	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Time from initiation of treatment to the occurrence of disease progression or death from any cause, whichever occurs first.	From treatment initiation until disease progression, death or last adequate disease assessment up to study termination.
Overall Survival	Time from the initiation of the treatment to death from any cause	From treatment initiation until death from any cause up to study termination.

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Comprehensive Cancer Network
• Investigators: Principal Investigator: Siqing Fu, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• M D Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Actual): September 30, 2024
• Study Completion (Actual): May 6, 2025

Study Registration Dates

• First Submitted: August 25, 2021
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): September 8, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Neoplastic Processes; Genital Neoplasms, Female; Uterine Neoplasms; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Endometrial Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab; futibatinib
• Other Study ID Numbers: 2020-0776; NCI-2021-09418 (Other Identifier: Clinical Trials Reporting Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No