Futibatinib + PD-1 Antibody for Esophageal Cancer

Not currently recruiting at 22 trial locations

Overseen By Taiho Oncology, Inc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Taiho Oncology, Inc.

Must not be taking: Anti-PD-1, PD-L1, FGF/FGFR

Disqualifiers: HIV, Hepatitis B/C, 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: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for esophageal cancer using two drugs: futibatinib (Lytgobi) and pembrolizumab (KEYTRUDA, a PD-1 antibody). The trial aims to evaluate the effectiveness and safety of these drugs when treating advanced esophageal cancer that cannot be surgically removed. Individuals diagnosed with metastatic esophageal cancer who have not yet received treatment for their advanced condition may qualify for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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, since prior systemic treatment for the disease is not allowed, you might need to stop certain treatments. Please consult with the trial coordinators for specific guidance.

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

Research has shown that the combination of futibatinib and pembrolizumab was tested for safety in earlier studies. In these studies involving patients with advanced or spreading solid tumors, the combination showed promising tumor-fighting results and was generally well-tolerated.

Some patients experienced side effects, which is common in cancer treatments. However, detailed safety data from earlier research suggest that the combination is manageable for patients. This indicates that while side effects can occur, they are usually not severe or unexpected.

In this trial, futibatinib is used with pembrolizumab and chemotherapy. Each treatment has been studied for safety individually, and the current study aims to better understand their combined safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Futibatinib and Pembrolizumab for esophageal cancer because it offers a novel approach compared to standard treatments like chemotherapy alone. Futibatinib targets specific pathways involved in cancer cell growth, potentially enhancing the efficacy of Pembrolizumab, an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. This combination aims to improve treatment responses and outcomes by synergistically attacking the cancer with both targeted therapy and immunotherapy, offering a promising new strategy for patients with esophageal cancer.

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

This trial will evaluate the combination of futibatinib and pembrolizumab for treating esophageal cancer. Research shows that using these two drugs together may help treat this condition. In earlier studies, patients who had not previously received immune therapy had a 39% chance of tumor shrinkage with this treatment. Additionally, 75% of patients experienced a halt in cancer growth. The treatment's side effects were expected and manageable. These results suggest that this combination could be effective for people with advanced esophageal cancer. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

Adults over 18 with advanced esophageal cancer that can't be removed by surgery or has spread, and who haven't had previous systemic treatments for it. Participants must have a certain PD-L1 score, good performance status, proper organ function, ability to take oral meds, and no other active cancers or significant health issues like HIV/Hepatitis B/C.

Inclusion Criteria

My organs are working well.

My pancreatic cancer is advanced and cannot be removed by surgery.

I am fully active or can carry out light work.

Exclusion Criteria

My cancer is advanced but can be removed or treated with radiation.

I have an autoimmune disease treated with medication in the last 2 years.

I have been treated with drugs targeting PD-1/PD-L1, FGF/FGFR, or T-cell receptors before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive futibatinib in combination with pembrolizumab plus standard of care chemotherapy for 6 cycles

18 weeks

6 cycles

Consolidation

Participants continue on futibatinib in combination with pembrolizumab

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Futibatinib
• Pembrolizumab

Trial Overview The trial is testing the combination of Futibatinib with standard-of-care immunotherapy (PD-1 antibody) and chemotherapy drugs in patients with solid tumors. It's an open-label study where everyone gets the treatment to see how effective and safe it is.

How Is the Trial Designed?

Group I: Cohort B Experimental Treatment 7 Interventions

Patients with PDAC will receive Futibatinib administered once daily on a continuous dosing regimen in combination with pembrolizumab plus mFOLFIRINOX for 6 cycles (induction phase) following by Futibatinib combination with pembrolizumab (consolidation phase) .

Group II: Cohort A Experimental Treatment 7 Interventions

Patients with Esophageal cancer (Adenocarcinoma or Squamous cell cancer) will receive Futibatinib administered once daily on a continuous dosing regimen in combination with pembrolizumab plus investigator choice of SoC chemotherapy (FP or mFOLFOX6) for 6 cycles (induction phase) following by Futibatinib combination with pembrolizumab (consolidation phase).

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?

Taiho Oncology, Inc.

Lead Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Published Research Related to This Trial

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

In a phase 2 trial involving 49 patients with refractory esophageal cancer, pembrolizumab showed a modest overall response rate of 8% and a median overall survival of 5.8 months, indicating limited efficacy as a single-agent treatment.

Baseline levels of circulating CXCL10 were identified as a strong predictor of survival, while other markers of T cell exhaustion were found to be elevated in PD-L1-positive patients, suggesting potential for combination therapies targeting these pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of pembrolizumab in refractory esophageal cancer with correlates of response and survival. de Klerk, LK., Patel, AK., Derks, S., et al.[2022]

In a study of 57 patients with advanced esophageal squamous cell carcinoma (ESCC), pembrolizumab combined with other treatments showed a high objective response rate of 74.1%, indicating its effectiveness in real-world clinical practice.

The treatment was generally safe, with common adverse events including leukopenia and nausea, and only 15.8% of patients experiencing severe (Grade III or higher) adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of combined treatment with pembrolizumab in patients with locally advanced or metastatic esophageal squamous cell carcinoma in the real world. Zhang, P., Hou, X., Cai, B., et al.[2022]

Preoperative treatment with pembrolizumab combined with chemoradiotherapy was found to be safe for 20 patients with resectable esophageal squamous cell carcinoma, with a high pathologic complete response (pCR) rate of 55.6%.

Despite some patients experiencing significant adverse events, including grade III lymphopenia in 65% of cases, the treatment did not delay surgery, indicating its feasibility for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). Li, C., Zhao, S., Zheng, Y., et al.[2021]

Pembrolizumab has been FDA-approved for treating PD-L1 positive, locally advanced or metastatic esophageal squamous cell carcinoma (ESCC), marking a significant advancement in targeted therapy options for this high-mortality cancer.

Despite the potential of targeted therapies, options for ESCC remain limited compared to esophageal adenocarcinoma (EAC), highlighting the need for genomic profiling and clinical trials to explore new treatments like CDK4/6 inhibitors and PARP inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esophageal carcinoma: Towards targeted therapies. Fatehi Hassanabad, A., Chehade, R., Breadner, D., et al.[2020]

Biologic therapies, particularly those targeting HER2 and VEGF, are showing promise in treating esophageal and gastric cancers, with trastuzumab and ramucirumab currently recommended by the NCCN for specific patient groups.

Recent studies indicate that other agents like pertuzumab, apatinib, and pembrolizumab may improve overall and progression-free survival, suggesting a growing role for targeted biologic therapies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. Samson, P., Lockhart, AC.[2020]

In a study of 15 patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC), Nimotuzumab combined with standard treatments resulted in a 100% objective response rate, with 33% achieving complete response and 67% showing partial response.

The treatment demonstrated a median overall survival of 26.8 months, with no severe adverse events (Grade III or IV), indicating that Nimotuzumab is well tolerated and does not add significant toxicity to the treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and tolerability of nimotuzumab in unresectable, locally advanced/metastatic esophageal cancer: Indian hospital-based retrospective evidence. Subramanian, S., Sridharan, N., Balasundaram, V., et al.[2022]

Nivolumab and pembrolizumab, both PD-1 inhibitors, have shown improved overall survival in patients with esophageal cancer, particularly in trials like ATTRACTION-3 and KEYNOTE-181, which involved patients with esophageal squamous cell carcinoma and those with high PD-L1 expression, respectively.

Ongoing trials are exploring the effectiveness of combining immune checkpoint inhibitors with traditional chemotherapy and radiotherapy, which may lead to better treatment options and outcomes for esophageal cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immuno-oncology for esophageal cancer. Yamamoto, S., Kato, K.[2021]

The KEYNOTE-975 trial is a Phase III study designed to evaluate the effectiveness of pembrolizumab combined with chemoradiotherapy as a first-line treatment for patients with locally advanced, unresectable esophageal or gastroesophageal junction cancer.

This trial aims to improve survival outcomes, as current treatments have poor results, and will measure overall survival and event-free survival as its primary endpoints.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma. Shah, MA., Bennouna, J., Doi, T., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.4047

Phase 1b study of futibatinib plus pembrolizumab with or ... Futi plus Pem with or without chemotherapy showed promising antitumor activity in adv or metastatic EC pts with both histology of scc and adeno.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05945823

Study Details | NCT05945823 | Phase 2 Futibatinib in ... This is a nonrandomized, uncontrolled, open-label, multicenter Phase 2 study to evaluate the efficacy, safety, and tolerability of futibatinib in combination ...

3. researchgate.net researchgate.net/publication/374878537_1532P_Phase_Ib_study_of_futibatinib_plus_pembrolizumab_in_patients_with_esophageal_carcinoma_Updated_results_of_antitumor_activity_and_tolerability_results_in_combination_with_chemotherapy

1532P Phase Ib study of futibatinib plus pembrolizumab in ... In ICI-naïve patients treated with futibatinib and pembro, the ORR was 39% with DCR of 75%. Patients who had previously received ICI had an ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02281-0/pdf

Updated results of antitumor activ Futibatinib plus pembrolizumab and chemo- therapy showed no new safety signals and manageable safety profile, with promising antitumor activity in pts with adv ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S014702722400093X

Current landscape of targeted therapy in esophageal ... We review the current progress and future perspectives of potential targeted therapies, including immunotherapy, for advanced ESCC.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)03210-0/fulltext

1241P Phase Ib study of futibatinib plus pembrolizumab in ... We report the safety and tolerability of FGFR inhibitor futibatinib plus pembrolizumab in pts with advanced (adv) or metastatic solid tumors.