Futibatinib + PD-1 Antibody for Esophageal Cancer

Recruiting at 21 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

53 Participants Needed

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.

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.

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. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination of Futibatinib and Pembrolizumab for esophageal cancer?

Pembrolizumab (Keytruda) has been approved for treating advanced esophageal cancer and has shown promising antitumor activity, especially when combined with other treatments like chemotherapy. This suggests potential effectiveness when used in combination with other drugs, such as Futibatinib, for esophageal cancer. ^{1 2 3 4 5}

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. ^{1 2 5 6 7}

Is the combination of Futibatinib and Pembrolizumab safe for treating esophageal cancer?

Pembrolizumab (also known as Keytruda) has been studied for safety in treating esophageal cancer, and it is generally well tolerated when combined with other treatments like chemotherapy and chemoradiotherapy. However, specific safety data for the combination of Futibatinib and Pembrolizumab is not provided in the available research. ^{1 2 5 6 7}

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. ^{1 2 4 8 9}

What makes the drug combination of Futibatinib and Pembrolizumab unique for esophageal cancer?

The combination of Futibatinib and Pembrolizumab is unique because it combines a targeted therapy (Futibatinib) with an immune checkpoint inhibitor (Pembrolizumab), potentially offering a novel approach by targeting specific cancer pathways and enhancing the immune system's ability to fight cancer, which is different from standard chemotherapy options. ^{1 2 4 8 9}

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.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

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

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. [2020]

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

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

Esophageal carcinoma: Towards targeted therapies. [2020]

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

Phase II study of pembrolizumab in refractory esophageal cancer with correlates of response and survival. [2022]

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]

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]

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

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). [2021]

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]

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

Immuno-oncology for esophageal cancer. [2021]