Futibatinib + Pembrolizumab for Liver Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Strong CYP3A4 inhibitors

Disqualifiers: Autoimmune disease, CNS metastasis, 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: 51

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for advanced liver cancer that has spread, specifically targeting liver cancer that tests positive for FGF19. It examines how two drugs, futibatinib (Lytgobi) and pembrolizumab (KEYTRUDA), work together to halt cancer growth and assist the immune system in attacking cancer cells. Participants must have FGF19 positive liver cancer that cannot be surgically removed or treated with other standard methods. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you must not have received systemic anticancer therapy, strong inhibitors and inducers, or sensitive substrates of CYP3A4 within 2 weeks prior to registration. 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?

Research has shown that pembrolizumab, one of the drugs in this trial, has produced positive results in treating advanced liver cancer. It has been used in other studies and is generally well-tolerated by patients, indicating its potential safety for humans.

Researchers are studying the effects of combining futibatinib with pembrolizumab on liver cancer. Although specific safety details for the combination are not yet available, the trial's Phase 2 status indicates that earlier studies have deemed it safe enough for testing in more people.

Both drugs have been used in other studies and are being evaluated for their combined potential to treat liver cancer, suggesting a level of safety that permits continued research in human trials. Always consult a healthcare provider for personal medical advice and to determine if joining a clinical trial is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about futibatinib combined with pembrolizumab for liver cancer because this duo offers a promising new approach. Futibatinib is a targeted therapy that inhibits FGFR (Fibroblast Growth Factor Receptor), which can be overactive in some cancers, potentially stopping cancer cells from growing. Pembrolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells more effectively. Together, these treatments could work synergistically to tackle liver cancer more effectively than current options, which primarily include chemotherapy, targeted therapies like sorafenib, and immunotherapies used individually. This combination aims to boost treatment effectiveness and improve patient outcomes.

What evidence suggests that futibatinib and pembrolizumab might be effective for liver cancer?

Research has shown that pembrolizumab effectively treats advanced liver cancer by helping the immune system attack cancer cells, potentially slowing disease progression. Futibatinib blocks certain enzymes necessary for cancer cell growth. This trial will evaluate the combination of futibatinib and pembrolizumab, targeting liver cancer with a protein called FGF19, which is linked to tumor growth. Early results suggest that using both futibatinib and pembrolizumab together might help manage advanced liver cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Nguyen Tran, MD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

Adults with advanced or metastatic liver cancer that tests positive for FGF19 and have already tried one systemic treatment. They must be able to take oral meds, provide consent, complete questionnaires, use contraception effectively, and meet specific health criteria like adequate blood counts and liver function.

Inclusion Criteria

Platelet count >= 75,000/mm^3 (=< 15 days prior to registration)

Calcium =< 1.5 x ULN (=< 15 days prior to registration)

Hemoglobin >= 8.0 g/dL (=< 15 days prior to registration)

Exclusion Criteria

Corrected QT interval using Fridericia's formula (QTcF) > 480 msec

You are currently receiving any experimental treatment for your cancer.

Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive futibatinib orally once daily and pembrolizumab intravenously every 21 days for cycles 1-9, and every 42 days for subsequent cycles, for up to 2 years

Up to 2 years

Every 21 days for cycles 1-9, every 42 days for subsequent cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 5 years

30 days post-treatment, every 9 weeks for 18 months, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Futibatinib
• Pembrolizumab

Trial Overview The trial is testing the combination of futibatinib (a drug blocking enzymes for cell growth) with pembrolizumab (an immunotherapy antibody). It aims to see if this combo can better attack cancer cells in patients with a particular type of liver cancer.

How Is the Trial Designed?

Group I: Treatment (futibatinib, pembrolizumab) Experimental Treatment 3 Interventions

Patients receive futibatinib PO QD on days 1-21 for cycles 1-9, and days 1-42 for subsequent cycles and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for cycles 1-9 and every 42 days for subsequent cycles for up to 2 years in the absence of disease progression or unacceptable toxicity.

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase 2 trial involving 104 patients with advanced hepatocellular carcinoma who had previously been treated with sorafenib, pembrolizumab demonstrated an objective response rate of 17%, indicating its potential efficacy as a treatment option for this patient population.

While 73% of patients experienced treatment-related adverse events, most were manageable, with serious events occurring in 15% of patients, suggesting that pembrolizumab is generally tolerable for patients with advanced liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Zhu, AX., Finn, RS., Edeline, J., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a phase II trial involving 51 patients with advanced hepatocellular carcinoma (HCC) who had not received prior systemic therapy, pembrolizumab demonstrated a 16% objective response rate, indicating its potential effectiveness in this patient population.

The treatment showed a median overall survival of 17 months and a median duration of response of 16 months, with a safety profile that included grade ≥3 treatment-related adverse events in 16% of patients, suggesting it is tolerable for use in advanced HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial. Verset, G., Borbath, I., Karwal, M., et al.[2023]

In a phase 3 study involving 794 patients with unresectable hepatocellular carcinoma, the combination of pembrolizumab and lenvatinib showed a median overall survival of 21.2 months, compared to 19.0 months for lenvatinib plus placebo, indicating a potential benefit in survival.

Despite the observed improvement in overall survival, the combination therapy did not meet the predefined significance thresholds for overall survival and progression-free survival, suggesting that it may not warrant a change in current treatment practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial. Llovet, JM., Kudo, M., Merle, P., et al.[2023]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

In a phase III trial involving 453 patients with advanced hepatocellular carcinoma (HCC), pembrolizumab significantly improved overall survival (14.6 months vs. 13.0 months for placebo) and progression-free survival (2.6 months vs. 2.3 months for placebo).

The objective response rate (ORR) was notably higher in the pembrolizumab group (12.7%) compared to the placebo group (1.3%), although treatment-related adverse events were more common in the pembrolizumab group (66.9% vs. 49.7% for placebo).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Versus Placebo as Second-Line Therapy in Patients From Asia With Advanced Hepatocellular Carcinoma: A Randomized, Double-Blind, Phase III Trial. Qin, S., Chen, Z., Fang, W., et al.[2023]

In the Asian subgroup of the KEYNOTE-240 trial, pembrolizumab significantly improved progression-free survival (PFS) to 2.8 months compared to 1.4 months for placebo, indicating its efficacy in treating advanced hepatocellular carcinoma (HCC).

The overall survival (OS) was also better with pembrolizumab at 13.8 months versus 8.3 months for placebo, with a manageable safety profile, as no treatment-related deaths occurred and most adverse events were of low grade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: A Subgroup Analysis of Asian Patients in the Phase 3 KEYNOTE-240 Trial. Kudo, M., Lim, HY., Cheng, AL., et al.[2023]

In a study of 104 patients with advanced hepatocellular carcinoma who had previously been treated with sorafenib, pembrolizumab showed an objective response rate of 18.3% and a median duration of response of 21 months, indicating its effectiveness as a treatment option.

After approximately 2.5 years of follow-up, pembrolizumab demonstrated durable anti-tumor activity with manageable safety, as most treatment-related adverse events were low grade, and no new safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated efficacy and safety of KEYNOTE-224: a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib. Kudo, M., Finn, RS., Edeline, J., et al.[2022]

Citations

1. trialx.com trialx.com/clinical-trials/listings/233766/futibatinib-and-pembrolizumab-for-treatment-of-advanced-or-metastatic-fgf19-positive-bclc-stage-a-b-or-c-liver-cancer/

Futibatinib and Pembrolizumab for Treatment of Advanced ... This phase II trial studies the effect of futibatinib and pembrolizumab in treating patients with FGF19 positive BCLC stage A, B, or C liver ...

2. mayo.edu mayo.edu/research/clinical-trials/cls-20513512

Clinical Trials This is a single-arm, two-stage, phase II trial to assess the efficacy of futibatinib plus pembrolizumab in advanced hepatocellular carcinoma ...

3. withpower.com withpower.com/trial/phase-3-carcinoma-hepatocellular-4-2021-72be9

Futibatinib + Pembrolizumab for Liver Cancer Research shows that Pembrolizumab, part of this drug combination, has shown positive results in treating advanced liver cancer, helping patients who have ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10052663/

Immunotherapy for advanced or recurrent hepatocellular ... Compared with other PD-1 inhibitors, camrelizumab experienced a significantly lower DCR (44.2% vs 55% with nivolumab[62] in sorafenib-patients and 47.7% vs 62% ...

5. 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.