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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether pemigatinib, a study drug, is effective for individuals with B-cell non-Hodgkin lymphomas that have recurred or are treatment-resistant. It targets those who have tried at least two other treatments without success. Individuals with certain types of lymphoma, such as MCL or MZL, who have measurable disease on a CT scan and require further treatment, might be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that pemigatinib has been studied for its safety and effectiveness in treating various conditions. In previous studies, researchers tested pemigatinib on patients with different types of cancer. Out of 635 patients who took the drug, 31% reported dry eyes, though most cases were mild. Another study found that patients generally tolerated pemigatinib well, with manageable side effects.

Pemigatinib is already FDA-approved for treating a specific type of bile duct cancer, indicating its safety for at least one condition. However, for those considering joining a trial, it's important to note that the safety of pemigatinib for lymphoma is still under investigation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pemigatinib is unique because it specifically targets and inhibits FGFR (fibroblast growth factor receptor), which is often involved in the growth and survival of cancer cells in certain types of lymphoma. Most current treatments for lymphoma, such as chemotherapy and immunotherapy, do not specifically target this pathway. Researchers are excited because pemigatinib's targeted mechanism could lead to more effective treatments with potentially fewer side effects compared to traditional therapies. This precision approach offers hope for improved outcomes in patients whose lymphoma is driven by FGFR alterations.

What evidence suggests that pemigatinib might be an effective treatment for B-cell non-Hodgkin lymphomas?

Research has shown that pemigatinib yields promising results in treating certain cancers. In other studies, it improved outcomes for patients with specific tumor types, with many experiencing slower cancer progression. The treatment was linked to a median progression-free survival of about 7.4 months, meaning patients lived for this time without their cancer worsening. Some patients also experienced long-lasting positive effects. This drug targets specific genetic changes in cancer cells, potentially stopping tumor growth. While these results are encouraging, they come from studies on other cancers. This trial will specifically investigate how pemigatinib works for B-cell non-Hodgkin lymphomas. ^{1 2 6 7 8}

Who Is on the Research Team?

Narendranath Epperla, M.D.

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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™) 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 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 (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]

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]

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]

Citations

1. hcp.pemazyre.com hcp.pemazyre.com/efficacy?role=910186760

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%.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9991984/

FDA Approval Summary: Pemigatinib for Previously Treated ... Ninety-six percent of patients had received prior platinum-based therapy including 76% with prior gemcitabine/cisplatin. Efficacy Results. In the first 107 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03011372

NCT03011372 | A Study to Evaluate the Efficacy and ... The purpose of this study is to evaluate the efficacy and safety of pemigatinib (INCB054828) in subjects with myeloid/lymphoid neoplasms with fibroblast growth ...

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

Real-world use of pemigatinib for the treatment of ... The median real-world progression-free survival (rwPFS) from the date of pemigatinib initiation was 7.4 months (95% CI: 6.4-8.6), and the real- ...

5. 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) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10405447/

Safety analysis of pemigatinib leveraging the US Food and ... Pemigatinib, the first targeted treatment for CCA in the United States, has been demonstrated to have a significant response rate and encouraging survival data ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/213736Orig1s000MultidisciplineR.pdf

213736Orig1s000 - accessdata.fda.gov • The primary data supporting the safety of pemigatinib for the proposed indication was provided from data derived from 146 patients with ...

8. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-fda-approval-pemazyrer-pemigatinib-first-and

Incyte Announces FDA Approval of Pemazyre® ... The FDA approval was based on data from the Phase 2 FIGHT-203 study, a multicenter open-label, single-arm trial that evaluated the safety and ...