Pemigatinib vs Chemotherapy for Bile Duct Cancer

(FIGHT-302 Trial)

No longer recruiting at 326 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the effectiveness and safety of a new drug, pemigatinib, against the standard chemotherapy combination of gemcitabine and cisplatin for treating bile duct cancer that cannot be surgically removed or has spread. It focuses on patients whose cancer has a specific change in the FGFR2 gene. Individuals diagnosed with cholangiocarcinoma (a type of bile duct cancer), who have not received prior treatment for it and have this FGFR2 genetic change, might be suitable candidates for the trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients the opportunity to access a potentially groundbreaking treatment.

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.

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

Research has shown that pemigatinib, a treatment for bile duct cancer, is already approved by the FDA for certain cases, indicating its safety has been studied. In earlier studies, some serious side effects, such as bile duct blockage and infections, were reported, but these occurred in only a small percentage of patients (4.1%). Most patients tolerated the treatment reasonably well.

Gemcitabine and cisplatin, the chemotherapy drugs used in this study, have been standard treatments for various cancers for many years. Their safety profile is well known, with common side effects like nausea and tiredness, typical for chemotherapy.

Overall, both treatment options in this study have safety data from previous research, which can help inform potential participants about what to expect. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for bile duct cancer?

Unlike the standard chemotherapy for bile duct cancer, which typically involves drugs like cisplatin and gemcitabine, pemigatinib is unique because it specifically targets a genetic alteration known as FGFR2 fusions or rearrangements. This targeted action means it can directly interfere with cancer cell growth and division in patients who have this genetic marker, potentially leading to more effective treatment outcomes. Researchers are excited about pemigatinib because it represents a shift towards personalized medicine, offering a more tailored approach compared to the broader mechanism of traditional chemotherapy.

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

Research has shown that pemigatinib, one of the treatments studied in this trial, may help treat bile duct cancer in patients with a specific genetic change called FGFR2 rearrangement. In earlier studies, 43% of these patients experienced noticeable tumor shrinkage. Many others maintained stable disease, meaning their cancer did not worsen. On average, patients lived longer without their cancer progressing. These encouraging results suggest pemigatinib could be a promising option for this type of bile duct cancer. Meanwhile, another arm of this trial will compare pemigatinib to the combination of gemcitabine and cisplatin, which serves as the active comparator. ^{4 5 6 7 8}

Who Is on the Research Team?

Peter Langmuir, MD

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

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.

Laboratory values at screening outside the protocol-defined range

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12078806/

Safety and efficacy of pemigatinib in patients with ...

pemigatinib achieved a 43% objective response rate in cholangiocarcinoma (CCA) patients with FGFR2 fusions or rearrangements. • Median progression-free survival ...

2.

hcp.pemazyre.com

hcp.pemazyre.com/efficacy?role=910186760

PEMAZYRE® (pemigatinib) Durable Efficacy Responses in ...

Fatal adverse reactions occurred in 4.1% of patients, including failure to thrive, bile duct obstruction, cholangitis, sepsis, and pleural effusion.

3.

esmoopen.com

esmoopen.com/article/S2059-7029(24)01257-2/fulltext

An open-label study of pemigatinib in cholangiocarcinoma

Median (range) follow-up for efficacy-assessable patients in cohort A was 42.9 (19.9-52.2) months. ORR (95% CI) based on IRC-assessed confirmed ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40386584/

Safety and efficacy of pemigatinib in patients with ...

Stable disease was observed in 36.9% of patients, while 14.9% experienced disease progression. Median progression-free survival (PFS) varied ...

5.

academic.oup.com

academic.oup.com/oncolo/article/30/1/oyae204/7739122

Real-world use of pemigatinib for the treatment of ...

Pemigatinib demonstrated efficacy in fibroblast growth factor receptor (FGFR)-altered cholangiocarcinoma (CCA) in the FIGHT-202 trial.

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38206555/

Pemigatinib: A Review in Advanced Cholangiocarcinoma

Median progression-free survival and overall survival at the time of the final analysis were 7.0 months and 17.5 months, respectively.

7.

hcp.pemazyre.com

hcp.pemazyre.com/safety-side-effects?gad_source=1&gad_campaignid=22041016789&gbraid=0AAAAACbr6MqPwI71yoHVns2wCjwsrXVLX

PEMAZYRE® (pemigatinib) Safety Profile & Side Effects

Fatal adverse reactions occurred in 4.1% of patients, including failure to thrive, bile duct obstruction, cholangitis, sepsis, and pleural effusion. Permanent ...

8.

pemazyre.com

pemazyre.com/

PEMAZYRE®: The first FDA-approved treatment for CCA

PEMAZYRE is a prescription medicine that is used to treat adults with bile duct cancer (cholangiocarcinoma) that has spread or cannot be removed by surgery.