Pemigatinib vs Chemotherapy for Bile Duct Cancer

(FIGHT-302 Trial)

Recruiting at 278 trial locations

Overseen By Incyte Corporation Call Center (US)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Incyte Corporation

Must not be taking: CYP3A4 inducers

Disqualifiers: CNS metastases, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 12 months

167 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called pemigatinib against the usual cancer treatment. It focuses on patients with advanced bile duct cancer who have a specific change in their genes. The goal is to see if pemigatinib is more effective and safer than the usual treatment. Pemigatinib is the first of its kind approved in the US, receiving approval recently.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain drugs like potent CYP3A4 inhibitors or inducers within 14 days before starting the study treatment. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Pemigatinib compared to chemotherapy for bile duct cancer?

Research shows that gemcitabine combined with cisplatin is a standard treatment for advanced biliary cancers, indicating its effectiveness. However, the studies do not provide direct evidence about Pemigatinib's effectiveness compared to this standard chemotherapy. ^{1 2 3 4 5}

What safety data exists for Pemigatinib, Cisplatin, and Gemcitabine in humans?

Cisplatin and its analogs, like carboplatin, have been studied for various cancers and are known to cause side effects like myelosuppression (a decrease in bone marrow activity), nausea, and vomiting, but they generally do not cause significant kidney or hearing damage. Gemcitabine, when combined with platinum compounds, can cause thrombocytopenia (low platelet count) but has shown improved safety profiles with adjusted dosing schedules. Pemigatinib, specifically, is not mentioned in the provided studies, so its safety profile is not detailed here. ^{6 7 8 9 10}

What makes the drug Pemigatinib unique for bile duct cancer treatment?

Pemigatinib is unique because it is a targeted therapy specifically for bile duct cancer patients with FGFR2 gene fusions or rearrangements, offering a personalized treatment option that differs from standard chemotherapy. It works by inhibiting the fibroblast growth factor receptor (FGFR), which is involved in cancer cell growth, and is taken orally, making it more convenient than traditional chemotherapy. ^{2 4 11 12 13}

Research Team

Peter Langmuir, MD

Principal Investigator

Incyte Corporation

Eligibility Criteria

Adults with previously untreated, inoperable or metastatic cholangiocarcinoma (bile duct cancer) and confirmed FGFR2 rearrangement can join. They must have a good performance status, meaning they're relatively active and able to care for themselves. Participants should be willing to prevent pregnancy.

Inclusion Criteria

Willingness to avoid pregnancy or fathering children

My cholangiocarcinoma is in stage IV and has not been treated.

My cancer has a specific genetic change known as FGFR2 rearrangement.

Exclusion Criteria

I have had treatment for cancer that couldn't be removed by surgery.

I have another cancer that is getting worse or needs treatment.

I have a history of calcium or phosphate balance issues leading to soft tissue calcification.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either pemigatinib or gemcitabine plus cisplatin chemotherapy

Up to approximately 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 12 months

Crossover

Participants who experience disease progression on gemcitabine + cisplatin may cross over to receive pemigatinib

Treatment Details

Interventions

• Cisplatin
• Gemcitabine
• Pemigatinib

Trial Overview The trial is testing the effectiveness and safety of pemigatinib compared to standard chemotherapy (gemcitabine plus cisplatin). It's for first-line treatment, which means it's the first therapy given after diagnosis.

Participant Groups

Group I: Pemigatinib Experimental Treatment 1 Intervention

Group II: Gemcitabine + Cisplatin Active Control 2 Interventions

Participants who experience disease progression while receiving gemcitabine + cisplatin or during the follow-up period and before starting a new anticancer therapy will be eligible to cross over and receive pemigatinib.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Findings from Research

A comprehensive analysis of 161 trials involving 6,337 patients found that the standard gemcitabine platinum (GP) chemotherapy has a median overall survival of 9.5 months and a tumor control rate of 63.5%.

Newer treatment regimens, including triplet combinations of gemcitabine, fluoropyrimidine, and platinum (GFP) or gemcitabine with targeted therapies, showed significantly better tumor control and overall survival compared to the standard GP regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy and targeted therapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Eckel, F., Schmid, RM.[2022]

In a phase 2 trial involving 150 patients with advanced biliary cancers, the addition of cetuximab to standard chemotherapy (gemcitabine and oxaliplatin) did not significantly improve progression-free survival compared to chemotherapy alone, with median progression-free survival of 6.1 months versus 5.5 months, respectively.

While cetuximab was well tolerated, the study found a higher incidence of grade 3-4 adverse events in the cetuximab group, suggesting that the standard chemotherapy regimen should remain the preferred treatment for advanced biliary cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial. Malka, D., Cervera, P., Foulon, S., et al.[2022]

In a study of 43 patients with unresectable biliary tract cancer, the combination of gemcitabine and cisplatin showed an overall response rate of 27.5%, indicating it has potential efficacy in treating this difficult-to-treat cancer.

The treatment was generally well-tolerated, with manageable side effects, including low rates of severe hematologic toxicity, suggesting that gemcitabine plus cisplatin could be a safe option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma. Thongprasert, S., Napapan, S., Charoentum, C., et al.[2022]

Combining gemcitabine with carboplatin has shown promising efficacy in treating advanced non-small-cell lung cancer, with recent studies indicating improved toxicity profiles compared to older regimens that used cisplatin.

New dosing schedules for gemcitabine, specifically administering it only on days 1 and 8 of a 21-day cycle, have reduced the risk of thrombocytopenia while maintaining effectiveness, making this combination a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in combination with new platinum compounds: an update. Gandara, DR., Edelman, MJ., Lara, PN., et al.[2022]

In a study of 31 patients with recurrent or metastatic head and neck cancer, carboplatin showed a 26% response rate (complete or partial responses) with a median duration of 4.5 months, indicating its potential effectiveness against advanced squamous-cell carcinoma.

Carboplatin demonstrated a different toxicity profile compared to cisplatin, with moderate bone marrow suppression being the main side effect, while avoiding nephrotoxicity and allowing for outpatient treatment, making it a safer option for patients with renal concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin (NSC-241-240): an active platinum analog for the treatment of squamous-cell carcinoma of the head and neck. Eisenberger, M., Hornedo, J., Silva, H., et al.[2017]

Pemigatinib (PEMAZYRE™) is the first targeted therapy approved in the USA for adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma that has a FGFR2 fusion or rearrangement, highlighting its significance in treating this challenging cancer.

The recommended dosage is 13.5 mg once daily for 14 days in a 21-day cycle, and it is currently being evaluated for use in other FGFR-driven cancers, indicating its potential broader application beyond cholangiocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemigatinib: First Approval. Hoy, SM.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Gemcitabine alone or in combination with cisplatin in patients with advanced or metastatic cholangiocarcinomas or other biliary tract tumours: a multicentre randomised phase II study - The UK ABC-01 Study. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Chemotherapy and targeted therapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial. [2022]

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

Pemetrexed and gemcitabine for biliary tract and gallbladder carcinomas: a North Central Cancer Treatment Group (NCCTG) phase I and II Trial, N9943. [2022]

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

Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical development of iproplatin (CHIP). [2012]

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

Platinum analogs in recurrent and advanced head and neck cancer: a Southwest Oncology Group and Wayne State University Study. [2013]

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

Gemcitabine in combination with new platinum compounds: an update. [2022]

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

Phase II study of CHIP chemotherapy in advanced adenocarcinomas of the upper gastrointestinal tract. [2019]

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

Carboplatin (NSC-241-240): an active platinum analog for the treatment of squamous-cell carcinoma of the head and neck. [2017]

11. England pubmed.ncbi.nlm.nih.gov

Evaluation of the pharmacokinetics of pemigatinib in patients with impaired hepatic or renal function. [2022]

12. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacological characteristics and clinical study results of Pemigatinib (Pemazyre® Tablets), a selective fibroblast growth factor receptor (FGFR) inhibitor]. [2021]

13. New Zealand pubmed.ncbi.nlm.nih.gov

Pemigatinib: First Approval. [2021]