Pemigatinib + Durvalumab for Liver Cancer

Overseen By Allison Lipps

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mehmet Akce

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Corneal disorders, Retinal disorders, Autoimmune disorders, 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

Compensation: Varies

Number of Visits: 1

Duration: 24 months

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, pemigatinib (a targeted therapy) and durvalumab (an immunotherapy), for intrahepatic cholangiocarcinoma, a specific type of liver cancer. Researchers aim to determine if this combination is effective for patients whose cancer has a particular genetic feature (FGFR-2 fusion or rearrangement). Suitable candidates have previously received certain cancer treatments and have this type of liver cancer that cannot be surgically removed. Those with this condition may consider this trial as an option. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use any potent CYP3A4 inhibitors or inducers within 14 days before starting the study drug, and you must have a washout period of at least 28 days after your last dose of anticancer therapy before starting the trial.

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

Research shows that the combination of pemigatinib and durvalumab is under study for safety in treating liver cancer, particularly in patients with specific genetic traits. Pemigatinib has been tested for other conditions, with common side effects including fatigue, low phosphate levels, and hair loss. Durvalumab, already approved for some cancers, is generally well-tolerated, with common side effects such as tiredness, loss of appetite, and nausea.

In this study phase, researchers closely observe how patients respond to the treatment over time to understand any side effects that may occur. Although previous studies have shown some side effects, they are considered manageable. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for liver cancer?

Researchers are excited about Pemigatinib combined with Durvalumab for liver cancer because it offers a unique approach compared to existing treatments. Unlike traditional therapies that might focus solely on immune checkpoint inhibition or kinase inhibition, this combination targets both fibroblast growth factor receptors (FGFR) through Pemigatinib and immune checkpoints with Durvalumab. This dual action could potentially enhance the body's immune response against cancer cells and inhibit tumor growth more effectively. Additionally, Pemigatinib's oral administration provides a convenient treatment method, complementing the intravenous delivery of Durvalumab in a manageable three-week cycle.

What evidence suggests that this treatment might be an effective treatment for liver cancer?

Research has shown that using pemigatinib and durvalumab together, as studied in this trial, may help treat intrahepatic cholangiocarcinoma, a type of liver cancer, especially in patients with a specific genetic change known as FGFR-2 fusion or rearrangement. Pemigatinib has effectively treated this cancer for several years, based on real-world evidence. Durvalumab, also used for other cancers like bladder cancer, may help the immune system find and attack cancer cells. Early studies have reported good results in controlling the cancer when these drugs are used together. This combination works in two ways: it blocks a key factor that helps cancer grow and boosts the body's immune response. ^{1 2 3 5 6}

Who Is on the Research Team?

Mehmet Akce, MD

Principal Investigator

Sponsor-Investigator

Are You a Good Fit for This Trial?

This trial is for patients who have already been treated for advanced intrahepatic cholangiocarcinoma, a type of liver cancer, and have specific genetic changes called FGFR-2 fusion or rearrangement. Participants must meet certain health standards and agree to regular visits with lab work.

Inclusion Criteria

1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

3. ECOG Performance Status of 0 or 1 within 7 days prior to Cycle 1 Day 1.

4. Body weight of \> 30 kg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pemigatinib and durvalumab combination therapy. Each cycle is 3 weeks, with pemigatinib administered orally for 2 weeks followed by 1 week off, and durvalumab administered intravenously every 3 weeks.

24 months

1 visit per cycle (in-person) with laboratory work

Follow-up

Participants are monitored for safety and effectiveness after treatment completion or discontinuation.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Pemigatinib

Trial Overview The study tests a combination of two drugs: Pemigatinib taken orally in cycles (2 weeks on, 1 week off) and Durvalumab given intravenously every 3 weeks. Patients will be monitored every 9 weeks to assess the treatment's effect on their disease over up to 24 months.

How Is the Trial Designed?

Group I: Pemigatinib + Durvalumab Experimental Treatment 2 Interventions

Pemigatinib 13.5 mg will be taken orally at the same time each day for 14 days (Day 1 through Day 14), followed by 7 days off treatment (Day 15 through Day 21) of each 21 day cycle. Durvalumab 1500 mg IV will be administered every 3 weeks on Day 1 of each 21-day cycle.

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

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Mehmet Akce

Lead Sponsor

Trials

2

Recruited

70+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

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

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

In a study of 112 patients receiving durvalumab for cancer treatment, 19% experienced liver injury, which was linked to higher rates of tumor progression and mortality, indicating that liver injury may be a significant concern in this patient population.

Among the liver injury cases, 29% were classified as probable drug-induced liver injury (DILI) related to durvalumab, but these cases were generally mild and self-limited, suggesting that while monitoring for liver injury is important, severe complications are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. Swanson, LA., Kassab, I., Tsung, I., et al.[2023]

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

Immune checkpoint inhibitors (ICIs) like anti-PD-1 and anti-CTLA-4 antibodies are effective treatments for metastatic melanoma and other advanced cancers, with biomarkers such as PD-L1 expression and tumor mutational load helping to predict patient response.

Current clinical practice uses biomarkers like pre-treatment tumor burden and serum lactate dehydrogenase levels to estimate the effectiveness of ICIs, while emerging research on the gut microbiome and imaging biomarkers may further enhance prediction of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment-A Review From the Melanoma Perspective and Beyond. Buder-Bakhaya, K., Hassel, JC.[2022]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

The DEDUCTIVE trial is a phase Ib study evaluating the safety and tolerability of combining durvalumab, a PD-L1 inhibitor, with tivozanib, a VEGFR tyrosine kinase inhibitor, in patients with advanced hepatocellular carcinoma (HCC).

Both durvalumab and tivozanib have shown effectiveness as single agents in HCC, but this trial aims to explore their concurrent use, particularly in treatment-naive patients and those who have progressed on other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, phase Ib/II, open-label study of tivozanib with durvalumab in advanced hepatocellular carcinoma (DEDUCTIVE). Mahmood, S., Li, D., Lee, A., et al.[2023]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

In a study of 83 patients with unresectable stage III non-small cell lung cancer (NSCLC) receiving durvalumab, 25.3% experienced pneumonitis, confirming the risk associated with this treatment.

The incidence of pneumonitis observed in this real-world setting aligns with findings from the PACIFIC trial, indicating that the safety profile of durvalumab is consistent in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. LeClair, JN., Merl, MY., Cohenuram, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06728410

NCT06728410 | A Phase II Study of Pemigatinib Plus ... This is a single arm phase II study of pemigatinib and durvalumab combination in patients with FGFR-2 fusion or rearrangement positive intrahepatic ...

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK596592/?report=classic

Clinical Review - Durvalumab (Imfinzi) - NCBI Bookshelf - NIH The amount of missing data was generally not reported for most efficacy outcomes; therefore, the impact of missing data on efficacy outcomes remains unknown.

3. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2023/PC0296-Imfinzi_combined.pdf

Durvalumab (Imfinzi) metastatic urothelial carcinoma, pending the results of clinical trials 20 Durvalumab has been previously ... long-term effectiveness of ...

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

PEMAZYRE® (pemigatinib) Durable Efficacy Responses in ... See efficacy data of PEMAZYRE, with 4+ years of real-world experience and 1000+ patients since FDA approval, as well as NCCN recommendations in CCA.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06530823

NCT06530823 | Pemigatinib Combined With Durvalumab ... Investigators will observe and document the objective tumor response rate of the participants, as well as progression-free survival (PFS), disease control rate ...

6. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/cholangiocarcinoma-

Cholangiocarcinoma Clinical Trials The purpose of this study is to assess the safety and preliminary efficacy of segmental ablative radioembolization in combination with Tremelimumab plus ...