Pemigatinib for Lymphoma

Recruiting at 1 trial location

Overseen By Narendranath Epperla, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Utah

Must not be taking: FGFR inhibitors, CYP3A4 inducers

Disqualifiers: HIV, Hepatitis B, CNS involvement, 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: Unknown

Duration: 8 months

27 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not clearly specify if you need to stop taking your current medications. However, you cannot take certain medications like potent CYP3A4 inhibitors or inducers within 14 days before starting the study drug. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What safety information is available for Pemigatinib in humans?

Pemigatinib has been studied in various clinical trials, showing that common side effects include high phosphate levels in the blood, hair loss, diarrhea, and nausea. Serious risks include eye problems and high phosphate levels, but overall, it has a favorable safety profile for patients with certain cancers. ^{1 2 3 4 5}

What makes the drug Pemigatinib unique for treating lymphoma?

Pemigatinib is unique because it targets specific genetic changes in cancer cells, particularly those involving the FGFR (fibroblast growth factor receptor) pathway, which is not commonly targeted by other lymphoma treatments. This makes it a novel option for patients with certain genetic profiles in their lymphoma. ^{6 7 8 9 10}

What is the purpose of this trial?

The purpose of this clinical trial is to learn if the study drug pemigatinib is effective in treating patients with relapsed or refractory B-cell non-Hodgkin lymphomas.

Research Team

Narendranath Epperla, M.D.

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for patients with specific types of lymphoma—Mantle Cell Lymphoma (MCL) or Marginal Zone Lymphoma (MZL)—that have either returned after treatment or haven't responded to previous treatments. Detailed eligibility criteria are not provided.

Inclusion Criteria

I had a stem cell transplant over 3 months ago.

My kidneys are functioning well enough to clear waste.

I need treatment that affects my whole body.

Exclusion Criteria

I have previously been treated with an FGFR inhibitor.

I have a serious heart condition.

I have a condition that affects how my body absorbs medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pemigatinib to assess its effectiveness in treating relapsed or refractory B-cell non-Hodgkin lymphomas

8 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Treatment Details

Interventions

• Pemigatinib

Trial Overview The trial is testing the effectiveness of pemigatinib, a drug that may inhibit cancer cell growth by blocking certain enzymes. It includes collecting biospecimens, bone marrow aspirations and biopsies, as well as CT and PET scans to monitor progress.

Participant Groups

Group I: Treatment: All Patients Experimental Treatment 1 Intervention

The study will investigate the effectiveness of pemigatinib.

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?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Narendranath Epperla

Lead Sponsor

Trials

3

Recruited

50+

Incyte Corporation

Industry 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

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]

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]

In a phase 1 study involving 44 Japanese patients with advanced solid tumors, pemigatinib showed manageable safety profiles with common side effects including hyperphosphatemia and dysgeusia, but no maximum tolerated dose was identified, leading to a recommended phase 2 dosage of 13.5 mg QD.

Preliminary efficacy results indicated that 16.7% of patients in the study achieved a partial response, with a median duration of response of 9.56 months, suggesting potential effectiveness in treating tumors with FGF/FGFR alterations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FIGHT-102: A phase 1 study of pemigatinib in Japanese patients with advanced malignancies. Fujiwara, Y., Kuboki, Y., Furukawa, M., et al.[2023]

Pemigatinib, a fibroblast growth factor receptor inhibitor, is primarily metabolized by CYP3A4, and its pharmacokinetics can be significantly affected by strong and moderate CYP3A4 inhibitors, necessitating dose adjustments when coadministered.

The developed physiologically based pharmacokinetic (PBPK) model accurately predicted drug-drug interactions with itraconazole and rifampin, indicating that while strong CYP3A4 inducers should be avoided, no dose adjustment is needed for weak CYP3A4 inhibitors or for P-gp/OCT2/MATE1 substrates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of drug-drug interaction potential for pemigatinib using physiologically based pharmacokinetic modeling. Ji, T., Chen, X., Yeleswaram, S.[2022]

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]

Pembrolizumab, a monoclonal antibody targeting PD-1, has shown significant clinical efficacy in treating Hodgkin Lymphoma and promising early results in certain subtypes of Non-Hodgkin Lymphoma, particularly those with genetic similarities to HL.

Current data suggest that pembrolizumab has a favorable safety profile and efficacy as a single agent in treating diffuse large B cell lymphomas, with future strategies likely to focus on biomarker-driven approaches and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. Sheikh, S., Kuruvilla, J.[2020]

Hodgkin lymphoma treatment is advancing with the integration of functional imaging, allowing for real-time adjustments to chemotherapy duration and intensity based on patient response, which can lead to more personalized care.

New therapeutic agents like brentuximab vedotin and checkpoint inhibitors (nivolumab and pembrolizumab) enhance treatment effectiveness while maintaining manageable toxicity levels, highlighting the importance of tailored treatment plans and ongoing patient assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Treatment Algorithms in Hodgkin Lymphoma: Too Much or Too Little? Spinner, MA., Advani, RH., Connors, JM., et al.[2019]

In a study of 64 hematopoietic cell lines, only 6 showed sensitivity to the BTK inhibitor tirabrutinib, indicating a need to understand resistance mechanisms in diffuse large B-cell lymphoma (DLBCL).

Combination therapies using tirabrutinib with drugs like idelalisib, palbociclib, or trametinib were found to enhance efficacy, particularly in an activated B-cell-like DLBCL cell line, suggesting potential strategies to overcome resistance in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responses to the Selective Bruton's Tyrosine Kinase (BTK) Inhibitor Tirabrutinib (ONO/GS-4059) in Diffuse Large B-cell Lymphoma Cell Lines. Kozaki, R., Vogler, M., Walter, HS., et al.[2022]

In a study involving 21 patients with relapsed or refractory non-Hodgkin lymphoma, apatinib demonstrated a promising overall response rate of 47.6%, indicating significant antitumor activity.

The treatment was generally well-tolerated, with most adverse events being mild to moderate, including proteinuria and hypertension, suggesting that apatinib could be a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open label, single-armed, exploratory study of apatinib (a novel VEGFR-2 tyrosine kinase inhibitor) in patients with relapsed or refractory non-Hodgkin lymphoma. Li, L., Xiao, S., Zhang, L., et al.[2022]

Apatinib, an oral tyrosine kinase inhibitor targeting VEGFR-2, demonstrated a promising overall response rate of 43.8% in patients with relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) in a phase II study involving 32 patients.

The treatment was associated with manageable adverse events, with no apatinib-related deaths reported, indicating a favorable safety profile for home administration of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apatinib in Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma: A Phase II, Open-Label, Single-Arm, Prospective Study. Ma, X., Li, L., Zhang, L., et al.[2022]

References

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

Pemigatinib: First Approval. [2021]

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

Population pharmacokinetic and exposure-response analyses of pemigatinib in patients with advanced solid tumors including cholangiocarcinoma. [2023]

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

FIGHT-102: A phase 1 study of pemigatinib in Japanese patients with advanced malignancies. [2023]

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

Evaluation of drug-drug interaction potential for pemigatinib using physiologically based pharmacokinetic modeling. [2022]

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

FDA Approval Summary: Pemigatinib for Previously Treated, Unresectable Locally Advanced or Metastatic Cholangiocarcinoma with FGFR2 Fusion or Other Rearrangement. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. [2020]

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

New Treatment Algorithms in Hodgkin Lymphoma: Too Much or Too Little? [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Responses to the Selective Bruton's Tyrosine Kinase (BTK) Inhibitor Tirabrutinib (ONO/GS-4059) in Diffuse Large B-cell Lymphoma Cell Lines. [2022]

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

An open label, single-armed, exploratory study of apatinib (a novel VEGFR-2 tyrosine kinase inhibitor) in patients with relapsed or refractory non-Hodgkin lymphoma. [2022]

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

Apatinib in Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma: A Phase II, Open-Label, Single-Arm, Prospective Study. [2022]