Pemigatinib for Colorectal Cancer

Not currently recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Academic and Community Cancer Research United

Must not be taking: CYP3A4 inhibitors, inducers

Disqualifiers: Brain metastases, Cardiovascular disease, HIV, Hepatitis, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: Approximately 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of pemigatinib (also known as Pemazyre or INCB054828) for individuals with colorectal cancer that has a specific genetic change in the FGFR gene. The cancer must have spread to other parts of the body or be inoperable. The drug aims to halt cancer cell growth by blocking FGFR, a protein that promotes cell growth. Suitable candidates have metastatic colorectal cancer or cancer that cannot be surgically removed and have not responded to standard treatments. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from a potentially effective new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use certain medications like potent CYP3A4 inhibitors or inducers within 14 days before joining the trial.

Is there any evidence suggesting that pemigatinib is likely to be safe for humans?

Research has shown that patients usually tolerate pemigatinib well. In studies with over 1,000 participants, pemigatinib proved effective over an extended period and is recommended by the National Comprehensive Cancer Network (NCCN) for certain types of cancer. However, a small number of patients reported serious side effects, such as stomach pain, fever, and kidney problems. Considering these potential risks and discussing them with a healthcare provider is important before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal cancer?

Unlike the standard chemotherapy treatments for colorectal cancer, pemigatinib is unique because it targets specific genetic alterations known as FGFR (fibroblast growth factor receptors). This precision targeting helps to directly interfere with cancer cell growth and proliferation, potentially leading to more effective treatment outcomes with fewer side effects. Researchers are excited about pemigatinib as it offers a new approach by focusing on these genetic pathways, paving the way for more personalized and targeted cancer therapy.

What evidence suggests that pemigatinib might be an effective treatment for colorectal cancer?

Research has shown that pemigatinib, which participants in this trial will receive, is being tested for its potential to treat colorectal cancer with specific genetic changes in the FGFR gene, crucial for cell growth. However, earlier studies found that pemigatinib did not significantly benefit patients with this type of colorectal cancer. On average, patients experienced about 9 weeks without cancer progression and lived about 8 months overall after starting treatment. While pemigatinib has shown promise in treating other cancers with FGFR changes, its effectiveness for this specific type of colorectal cancer remains unclear based on current evidence. ^{1 3 4 6 7}

Who Is on the Research Team?

Kristen K Ciombor

Principal Investigator

Academic and Community Cancer Research United

Are You a Good Fit for This Trial?

This trial is for adults with metastatic or unresectable colorectal cancer that has specific FGFR gene alterations. Participants must have tried and not responded to standard treatments, including chemotherapy and targeted therapies like anti-VEGF and anti-EGFR if applicable. They should be in a relatively stable condition (ECOG performance status of 0, 1, or 2) with adequate organ function and no significant heart issues, eye disorders, or other serious health problems.

Inclusion Criteria

Patient must have received and progressed on, or be intolerant to, each of the following treatments for mCRC (or have contraindication to these treatments): Fluoropyrimidine, Oxaliplatin, Irinotecan, Anti-VEGF (vascular endothelial growth factor) monoclonal antibody, if eligible for this therapy, Anti-EGFR (epidermal growth factor receptor) monoclonal antibody, if eligible for this therapy, Measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2, Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 28 days prior to registration), Platelet count >= 100,000/mm^3 (obtained =< 28 days prior to registration), Hemoglobin >= 9.0 g/dL (obtained =< 28 days prior to registration), Total bilirubin =< 1.5x upper limit of normal (ULN), or =< 2.5x ULN if patient has Gilbert syndrome or disease involving the liver (obtained =< 28 days prior to registration), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5x ULN (or =< 5x ULN in presence of suspected liver metastases) (obtained =< 28 days prior to registration), Serum phosphate < institutional ULN (obtained =< 28 days prior to registration), Serum calcium within institutional normal range, or serum albumin-corrected calcium within institutional normal range (if serum albumin is outside of the institutional normal range) (obtained =< 28 days prior to registration), Potassium levels > institutional lower limit of normal (supplementation can be used to correct potassium level during screening) (obtained =< 28 days prior to registration), Serum creatinine =< 1.5x ULN, or calculated creatinine clearance > 30 mL/min using the Cockcroft-Gault formula or 24-hours urine collection analysis (obtained =< 28 days prior to registration), Corrected QT interval (QTc) by Fridericia's method (QTcF) assessed by electrocardiogram (ECG) completed =< 28 days prior to registration, and resulted as: QTcF =< 450 msec in men, or QTcF =< 470 msec in women, Negative serum pregnancy test completed =< 7 days prior to registration, for women of childbearing potential only, Willing to provide tissue and blood samples for correlative research purposes, Willing to allow transfer of tissue and blood samples, clinical information, and outcome data collected from this trial for future research

My cancer has a specific genetic change in the FGFR1-3 genes.

Registered to Colorectal and Liquid Biopsy Molecularly Assigned Therapy (COLOMATE) Academic and Community Cancer Research United (ACCRU)-GI-1611 and COLOMATE Companion Trial Recommendation Form indicates patient qualifies to be screened for a COLOMATE companion trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pemigatinib orally once daily on days 1-21, with treatment repeating every 21 days for up to 35 cycles

Approximately 24 months

Regular visits every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

36 months

Follow-up every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Pemigatinib

Trial Overview

The trial is testing the effectiveness of Pemigatinib—a drug designed to block FGFR which tumors need to grow—in patients whose colorectal cancer has spread and cannot be surgically removed. It's a phase II study focusing on how well this treatment works when traditional options fail due to specific genetic changes in the tumor.

How Is the Trial Designed?

Group I: Treatment (pemigatinib) Experimental Treatment 2 Interventions

Patients receive pemigatinib PO QD on days 1-21. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

Pemigatinib is already approved in United States for the following indications:

Approved in United States as Pemazyre for:

• Unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement
• Relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement

Who Is Running the Clinical Trial?

Academic and Community Cancer Research United

Lead Sponsor

Trials

54

Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 I trial involving 12 Chinese patients with advanced solid tumors, pemigatinib showed acceptable safety and tolerability, with 25% of patients experiencing grade 3 or higher adverse events.

The drug demonstrated preliminary efficacy, with partial responses observed in two patients with specific FGFR mutations, indicating its potential as a targeted therapy for tumors with FGF/FGFR alterations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and efficacy of pemigatinib (a selective inhibitor of fibroblast growth factor receptor 1-3) monotherapy in Chinese patients with advanced solid tumors: a phase i clinical trial. Deng, T., Zhang, L., Shi, Y., et al.[2023]

Pemigatinib is an effective oral treatment for advanced/metastatic cholangiocarcinoma (CCA) with FGFR2 alterations, showing a favorable benefit-risk profile at a dose of 13.5 mg once daily in 21-day cycles based on a refined pharmacokinetic model from 467 participants.

The study found that pemigatinib exposure is linked to both efficacy and safety, with a bell-shaped relationship between drug levels and response rates, as well as treatment-emergent adverse events like decreased appetite and nausea, although these relationships were not clinically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic and exposure-response analyses of pemigatinib in patients with advanced solid tumors including cholangiocarcinoma. Gong, X., Akil, A., Ndi, A., et al.[2023]

Pemigatinib (PEMAZYRE) received FDA accelerated approval for treating adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion, based on a trial involving 107 patients, showing an overall response rate of 36% and a median duration of response of 9.1 months.

The most common side effects of pemigatinib include hyperphosphatemia and ocular toxicity, highlighting the importance of monitoring these risks during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pemigatinib for Previously Treated, Unresectable Locally Advanced or Metastatic Cholangiocarcinoma with FGFR2 Fusion or Other Rearrangement. Patel, TH., Marcus, L., Horiba, MN., et al.[2023]

Pemigatinib is an effective treatment for patients with advanced cholangiocarcinoma that have FGFR2 genomic alterations, showing a 35.5% objective response rate after a median follow-up of 17.8 months in a phase II study.

The drug has a manageable safety profile, with common side effects including changes in blood phosphate levels, fatigue, and gastrointestinal issues, leading to its accelerated approval by the FDA for specific cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A drug safety evaluation of pemigatinib for advanced cholangiocarcinoma. Uson, PLS., Bearss, J., Babiker, HM., et al.[2023]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40515475/

A phase II, multicenter, single-arm study of pemigatinib in ...

Pemigatinib monotherapy did not lead to objective responses in patients with chemorefractory metastatic colorectal cancer harboring FGF/FGFR alterations.

2.

hcp.pemazyre.com

hcp.pemazyre.com/efficacy

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

Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, RPED occurred in 11% of patients, including Grade 3-4 RPED in 1.3%.

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.139

A phase II single-arm study of the FGFR inhibitor ...

Median progression-free survival was 9.1 weeks (95% CI, 7.9-not evaluable [NE]), and median overall survival was 7.9 months (95% CI, 3.4-NE).

4.

hcp.pemazyre.com

hcp.pemazyre.com/4year-analysis

long-term data: - 4-year follow-up analysis

• The major efficacy outcome measures were overall response rate (ORR) and duration of response (DoR), as determined by independent review committee (IRC) ...

5.

nature.com

nature.com/articles/s41591-024-02934-7

phase 2 FIGHT-207 basket trial

Here we studied pemigatinib, a selective, potent, oral FGFR1–FGFR3 inhibitor, in the phase 2 FIGHT-207 basket study of FGFR-altered advanced solid tumors.

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04096417

NCT04096417 | Pemigatinib for the Treatment of Metastatic ...

This phase II trial studies how well pemigatinib works in treating patients with colorectal cancer with mutations (alterations) in a FGFR gene and that has ...

7.

mayo.edu

mayo.edu/research/clinical-trials/cls-20490903

Pemigatinib to Treat Metastatic or Unresectable Colorectal ...

The purpose of this study is to assess how well Pemigatinib works in treating patients with colorectal cancer with mutations (alterations) in a FGFR gene and ...