Futibatinib + PD-1 Antibody for Esophageal Cancer

Recruiting in Palo Alto (17 mi)

+21 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Taiho Oncology, Inc.

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a nonrandomized, uncontrolled, open-label, multicenter Phase 2 study to evaluate the efficacy, safety, and tolerability of futibatinib in combination with PD-1 antibody-based SoC therapy in adult patients with solid tumors.

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.

What data supports the idea that Futibatinib + PD-1 Antibody for Esophageal Cancer is an effective drug?

The available research shows that pembrolizumab, a PD-1 antibody, has been approved for treating esophageal cancer, especially when combined with other chemotherapy drugs. It has shown promising results in improving survival rates for patients with advanced stages of the disease. Although the specific combination of Futibatinib and PD-1 antibody isn't directly mentioned, pembrolizumab's effectiveness in esophageal cancer treatment suggests potential benefits when used in combination with other agents.

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

The safety data for Pembrolizumab (Keytruda) in esophageal cancer is well-documented. It has been approved for use in metastatic or locally advanced esophageal or gastroesophageal junction cancer, often in combination with chemotherapy. Studies have shown that Pembrolizumab is well tolerated and provides promising antitumor activity. The KEYNOTE-975 trial is investigating its combination with chemoradiotherapy, focusing on safety and efficacy. However, specific safety data for the combination of Futibatinib and Pembrolizumab is not detailed in the provided research.

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Is the drug combination of Futibatinib and Pembrolizumab promising for esophageal cancer?

Yes, the drug combination of Futibatinib and Pembrolizumab is promising for esophageal cancer. Pembrolizumab has been approved for treating esophageal cancer and has shown improved survival rates. Combining it with Futibatinib could enhance its effectiveness, making it a promising option for patients.

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Eligibility Criteria

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.

I am fully active or can carry out light work.

I can take pills by mouth.

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.

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Moffitt Cancer Center and Research Institute Tampa, FL

Mount Sinai Comprehensive Cancer Center Miami Beach, FL

Blue Ridge Cancer Care Roanoke, VA

Virginia Mason Medical Center Seattle, WA

More Trial Locations

Who Is Running the Clinical Trial?

Taiho Oncology, Inc. Lead Sponsor

References

1. China pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. [2020] Biologic agents, including targeted antibodies as well as immunomodulators, are demonstrating unparalleled development and study across the entire spectrum of human malignancy. This review summarizes the current state of biologic therapies for esophageal, esophagogastric, and gastric malignancies, including those that target human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), c-Met, mechanistic target of rapamycin (mTOR) and immunomodulators. We focus primarily on agents that have been included in phase II and III clinical trials in locally advanced, progressive, or metastatic esophageal and gastric malignancies. At this time, only two biologic therapies are recommended by the National Comprehensive Cancer Network (NCCN): trastuzumab for patients with esophageal/esophagogastric or gastric adenocarcinomas with HER2 overexpression and ramucirumab, a VEGFR-2 inhibitor, as a second-line therapy for metastatic disease. However, recent reports of increases in overall and progression-free survival for agents including pertuzumab, apatinib, and pembrolizumab will likely increase the use of targeted biologic therapy in clinical practice for esophageal and gastric malignancies.

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023] Pembrolizumab (Keytruda) has been approved to treat metastatic or locally advanced esophageal or gastroesophageal junction cancer. It is used in combination with platinum- and fluoropyrimidine-based chemotherapy.

3. Netherlands pubmed.ncbi.nlm.nih.gov

Esophageal carcinoma: Towards targeted therapies. [2020] Patients with esophageal cancer are confronted with high mortality rates. Whether it is esophageal squamous cell carcinoma (ESCC) or esophageal adenocarcinoma (EAC), patients usually present at advanced stages, with treatment options traditionally involving chemotherapy in metastatic settings. With the comprehensive genomic characterization of esophageal cancers, targeted therapies are gaining interest and agents such as ramucirumab, trastuzumab and pembrolizumab are already being used for the treatment of EAC.

4. England pubmed.ncbi.nlm.nih.gov

Phase II study of pembrolizumab in refractory esophageal cancer with correlates of response and survival. [2022] Immune checkpoint inhibitors have revolutionized cancer treatment, but the benefits in refractory patients with esophageal cancer have been modest. Predictors of response as well as new targets for novel therapeutic combinations are needed. In this phase 2 clinical trial, we tested single-agent pembrolizumab in patients with advanced esophageal cancer, who received at least one prior line of therapy.

5. England pubmed.ncbi.nlm.nih.gov

KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma. [2021] Despite curative-intent treatment, most patients with locally advanced esophageal cancer will experience disease recurrence or locoregional progression, highlighting the need for new therapies. Current guidelines recommend definitive chemoradiotherapy in patients ineligible for surgical resection, but survival outcomes are poor. Pembrolizumab is well tolerated and provides promising antitumor activity in patients with previously treated, advanced, unresectable esophageal/esophagogastric junction cancer. Combining pembrolizumab with chemoradiotherapy may further improve outcomes in the first-line setting. Here, we describe the design and rationale for the double-blind, Phase III, placebo-controlled, randomized KEYNOTE-975 trial investigating pembrolizumab in combination with definitive chemoradiotherapy as first-line treatment in patients with locally advanced, unresectable esophageal/gastroesophageal junction cancer. Overall survival and event-free survival are the dual primary end points. Clinical trial registration: NCT04210115 (ClinicalTrials.gov).

6. China 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. [2022] Treatments for patients with advanced esophageal cancer are still limited. Pembrolizumab has demonstrated antitumor activity in patients with advanced esophageal cancer in previous studies. Few studies have assessed safety and efficacy in routine clinical practice. We investigated the real-world outcomes of pembrolizumab for patients with advanced esophageal cancer.

7. England pubmed.ncbi.nlm.nih.gov

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). [2021] To investigate the safety and activity of preoperative pembrolizumab combined with chemoradiotherapy for resectable oesophageal squamous cell carcinoma (ESCC) (ClinicalTrials.gov number, NCT03792347).

8. India pubmed.ncbi.nlm.nih.gov

Effectiveness and tolerability of nimotuzumab in unresectable, locally advanced/metastatic esophageal cancer: Indian hospital-based retrospective evidence. [2022] Epidermal growth factor receptor (EGFR) is overly expressed in esophageal squamous cell carcinoma (ESCC) and is important prognostic and predictive biomarker. Nimotuzumab is a humanized anti-EGFR monoclonal antibody and has documented promising clinical outcomes and survival rates in various solid tumors with high EGFR expression.

9. England pubmed.ncbi.nlm.nih.gov

Immuno-oncology for esophageal cancer. [2021] Esophageal cancer (EC) is the seventh most common cancer, with a poor prognosis for metastatic EC patients and limited effective drugs for treatment. Nivolumab and pembrolizumab, monoclonal antibodies that inhibit interactions of PD-1 and its ligand (PD-L1), which induce lymphocyte activation, have antitumor activity. The ATTRACTION-3 trial compared nivolumab with taxane after first-line chemotherapy and demonstrated superior overall survival (OS) for esophageal squamous cell carcinoma. The KEYNOTE-181 trial that compared pembrolizumab with chemotherapy demonstrated superior OS for EC with a PD-L1 combined positive score ≥10. Trials to evaluate efficacy of combined cytotoxic agents and immune checkpoint inhibitors (ICI) as first-line chemotherapies, ICI-containing chemoradiotherapy, and pre/postoperative chemotherapy are ongoing and might provide important data to improve clinical outcomes.