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

14 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies the effect of combining futibatinib and pembrolizumab in treating patients with advanced liver cancer that is FGF19 positive. Futibatinib blocks enzymes needed for cancer cell growth, while pembrolizumab helps the immune system attack the cancer. The goal is to see if this combination can effectively treat these patients.

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.

What data supports the idea that Futibatinib + Pembrolizumab for Liver Cancer is an effective treatment?

The available research shows that pembrolizumab, one of the drugs in the combination, has been effective in treating advanced liver cancer, especially in patients who have already tried other treatments like sorafenib. Studies like KEYNOTE-224 and KEYNOTE-240 have shown that pembrolizumab can help control the disease and is generally well-tolerated by patients. However, there is no specific data provided on the combination of Futibatinib and Pembrolizumab for liver cancer, so we can't directly compare it to other treatments based on the information available. ^{1 2 3 4 5}

What safety data exists for the treatment of Futibatinib and Pembrolizumab for liver cancer?

The safety data for Pembrolizumab (also known as KEYTRUDA or MK-3475) has been evaluated in various trials for different cancers, including hepatocellular carcinoma (HCC). In the KEYNOTE-224 trial, Pembrolizumab was assessed for safety in patients with advanced HCC previously treated with sorafenib. Additionally, a phase III trial compared Pembrolizumab to a placebo in Asian patients with advanced HCC. Common adverse reactions to Pembrolizumab include fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions can include pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. These safety profiles are based on trials for various cancers, not specifically for the combination of Futibatinib and Pembrolizumab in liver cancer. ^{2 6 7 8 9}

Is the drug Futibatinib, Pembrolizumab a promising treatment for liver cancer?

Yes, the drug Futibatinib, Pembrolizumab is promising 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 already tried other treatments. ^{1 2 3 4 7}

Research Team

Nguyen Tran, MD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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 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 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]

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]

References

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

Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial. [2023]

2. England 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. [2022]

3. England 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. [2023]

4. England 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. [2022]

5. Switzerland 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. [2023]

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

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

7. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

8. United States 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. [2023]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]