Pemigatinib + Atezolizumab + Bevacizumab for Bile Duct Cancer

Overseen By Sunyoung Lee, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Chemotherapy, FGFR inhibitors, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—pemigatinib, atezolizumab, and bevacizumab—to determine their effectiveness in controlling bile duct cancer, known as cholangiocarcinoma. Researchers explore different doses of pemigatinib, a targeted therapy, to identify the optimal level for effectiveness and safety. The trial seeks participants with advanced or metastatic cholangiocarcinoma who have a genetic feature called FGFR2 fusion or rearrangement and have already tried standard treatments. This offers individuals whose cancer progresses despite previous treatments a chance to potentially benefit from a new combination approach. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications, like potent CYP3A4 inhibitors or inducers, and those that increase serum phosphorus or calcium, are prohibited. 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 this trial's treatments are likely to be safe?

Research has shown that pemigatinib is generally manageable for patients, with few new safety concerns over long-term use. However, a small number of patients experienced serious side effects, such as blocked bile ducts and severe infections.

Studies on atezolizumab, when combined with other treatments, suggest it can be safe for people with advanced biliary tract cancer. The combination with bevacizumab has shown promising results and is generally safe.

Bevacizumab, used in various cancer treatments, has been shown to slow cancer growth. Safety data suggest it is well-tolerated when combined with other treatments.

Overall, these medications have been used in other cancer treatments, providing some context for their safety. However, since this trial is still in the early stages, more data will help confirm their safety when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for bile duct cancer because it brings together three powerful drugs: pemigatinib, atezolizumab, and bevacizumab. Unlike traditional chemotherapy, which kills rapidly dividing cells, pemigatinib targets a specific genetic mutation known as FGFR2, which is involved in tumor growth. Atezolizumab is an immunotherapy that boosts the body's immune system to better recognize and attack cancer cells. Bevacizumab works by cutting off the blood supply tumors need to grow. This multi-pronged approach not only targets the cancer directly but also supports the immune system and disrupts the tumor's blood supply, offering a potentially more effective treatment than current options.

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

Research has shown that pemigatinib may effectively treat cholangiocarcinoma, a type of bile duct cancer. In earlier studies, it helped shrink tumors in 43% of patients with specific genetic traits linked to this cancer. In this trial, participants in Part 1 will receive varying doses of pemigatinib to determine the optimal dose. Atezolizumab and bevacizumab, when used together, have also reduced tumor size and delayed cancer progression. For instance, some patients experienced a delay in cancer growth for 3 to 7.2 months. These treatments block the pathways cancer cells use to grow and spread, providing a comprehensive approach to managing this challenging cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Sunyoung Lee, MD,PHD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced cholangiocarcinoma, a type of bile duct cancer that has an FGFR2 fusion. Participants should not have had prior treatment with similar drugs and must be in good physical condition to handle the treatments.

Inclusion Criteria

Has disease that is measurable per the RECIST v1.1.

Has a negative human immunodeficiency virus (HIV) test at screening with specific exceptions.

I tested negative for hepatitis B or am being treated for chronic HBV.

Exclusion Criteria

Is pregnant or breastfeeding or intends to become pregnant during study treatment or within a defined timeframe.

I had a severe infection recently.

I have had significant wounds, ulcers, or fractures recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive pemigatinib at varying doses to determine the recommended phase 2 dose in combination with atezolizumab and bevacizumab

Up to 6 months

Treatment Part 2

Participants receive pemigatinib at the recommended dose determined in Part 1, in combination with atezolizumab and bevacizumab

Up to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab
• Pemigatinib

Trial Overview The study tests if pemigatinib combined with atezolizumab and bevacizumab can manage advanced cholangiocarcinoma better than current standard treatments. It's a Phase II trial, which means it's checking the effectiveness and safety of this drug combo.

How Is the Trial Designed?

Group I: Part 2 Experimental Treatment 3 Interventions

Participants in Part 2, you will receive pemigatinib at the recommended dose that was found in Part 1.

Group II: Part 1 Experimental Treatment 3 Interventions

Participants enrolled in Part 1, the dose of pemigatinib the participant receive will depend on when the participant join this study. Up to 2 dose levels of pemigatinib will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the highest dose level of pemigatinib. A second group will receive a lower dose of pemigatinib than the group before it, if intolerable side effects are seen.

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8670844/

Multicenter randomized phase II trial of atezolizumab with ... Seventy-seven patients were randomized and received study therapy. The trial met its primary endpoint, with a median PFS of 3.65 months in the ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00337

Atezolizumab Plus Chemotherapy With or Without ... In unselected patients with advanced BTC, adding bevacizumab to atezolizumab plus CisGem modestly improves PFS but not OS.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38059651/

Atezolizumab and bevacizumab for non-resectable or ... Patients treated with atezolizumab/bevacizumab in the first line had a median OS of 13 months and a median PFS of 3 months. Among the 7 patients receiving ...

4. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/a-study-of-atezolizumab-with-or-without-bevacizumab-in--17170.html

Clinical Trial – Biliary Tract Cancer – Efficacy and Safe... The purpose of this clinical trial is to compare the effects, good or bad, of bevacizumab plus atezolizumab, cisplatin and gemcitabine versus atezolizumab, ...

5. digestivecancers.eu digestivecancers.eu/progress-in-liver-and-bile-duct-cancer-new-insights-from-esmo-2025/

Progress in Liver and Bile Duct Cancer: New Insights from ... Results were highly encouraging: 80% of patients experienced tumour shrinkage, and several who were initially inoperable became eligible for ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34377158/

IMbrave 151: a randomized phase II trial of atezolizumab ... IMbrave 151: a randomized phase II trial of atezolizumab combined with bevacizumab and chemotherapy in patients with advanced biliary tract ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03201458

Atezolizumab With or Without Cobimetinib in Treating ... This randomized phase II trial studies how well atezolizumab with or without cobimetinib works in treating patients with bile duct cancer that has spread to ...

8. journals.sagepub.com journals.sagepub.com/doi/10.1177/17562848231160630

Efficacy and safety of a triple combination of atezolizumab ... The triple combination of atezolizumab, bevacizumab, and GEMOX may be efficacious and safe for patients with advanced BTC.