Zanzalintinib + Durvalumab for Liver Cancer

Overseen By Amit Mahipal, MD, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Amit Mahipal

Must be taking: Durvalumab

Must not be taking: Anticoagulants, Platelet inhibitors

Disqualifiers: Brain metastases, Uncontrolled hypertension, 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: 4

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if adding the drug zanzalintinib to the existing treatment with durvalumab extends the lives of people with advanced liver cancer. Participants should currently be receiving durvalumab and have previously received tremelimumab with durvalumab. This study suits those with advanced liver cancer that cannot be surgically removed and who have experienced stable results or improvement with prior treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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

The trial requires participants to continue taking durvalumab, but it does not specify if you need to stop other medications. However, you cannot take certain investigational agents or complementary medications like herbal supplements within two weeks before starting the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have tested the combination of zanzalintinib and durvalumab for safety in treating advanced liver cancer. Research shows that patients generally tolerate this combination well. Specifically, earlier studies found that many patients taking durvalumab maintained stable liver function, indicating a positive safety profile. While zanzalintinib remains under study and lacks FDA approval for this cancer type, durvalumab is already approved for advanced liver cancer, confirming its thorough safety testing. However, as with any new treatment, side effects may occur, so discussing these with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of durvalumab and zanzalintinib for liver cancer because it offers a unique approach compared to standard treatments like sorafenib or lenvatinib. Unlike these therapies, which primarily target specific proteins to inhibit tumor growth, durvalumab is an immunotherapy that boosts the body's immune system to fight cancer cells, while zanzalintinib is a new tyrosine kinase inhibitor designed to target multiple pathways involved in cancer progression. This dual approach not only aims to directly attack the cancer cells but also empowers the immune system to sustain a long-term defense against the tumor, potentially improving outcomes for patients with liver cancer.

What evidence suggests that zanzalintinib with durvalumab might be an effective treatment for advanced liver cancer?

Research has shown that combining the drugs zanzalintinib and durvalumab might benefit people with advanced liver cancer. In this trial, participants will receive both zanzalintinib and durvalumab. Studies have found that using zanzalintinib with durvalumab can target and attack cancer cells more effectively. Durvalumab alone has already helped some liver cancer patients live longer. Adding zanzalintinib is expected to enhance these benefits. Previous research on similar drug combinations has shown promising results. The goal is that using these drugs together could improve survival rates by more effectively combating the cancer. ^{2 3 4 5 6}

Who Is on the Research Team?

Amit Mahipal, MD, MBBS

Principal Investigator

Case Comprehensive Cancer Center, University Hospitals

Are You a Good Fit for This Trial?

This trial is for people with advanced liver cancer who have already been treated with tremelimumab and durvalumab, and are currently on durvalumab. It's to see if adding a new drug called zanzalintinib can help them live longer.

Inclusion Criteria

Sexually active fertile participants and their partners must agree to use highly effective method of contraception

At least one index lesion that is measurable based on RECIST 1.1

I am older than 18.

Exclusion Criteria

Participants receiving any other investigational agents concurrently for cancer treatment

Pregnant or breastfeeding women

Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms within 14 days before first dose of study treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a treatment regimen of durvalumab and zanzalintinib. Each treatment cycle is 28 days and continues until disease progression, death, or withdrawal.

16 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and overall survival.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Zanzalintinib

Trial Overview The study tests the combination of zanzalintinib (an investigational drug not yet approved by the FDA) with the FDA-approved durvalumab in patients previously treated for advanced liver cancer, aiming to improve survival rates.

How Is the Trial Designed?

Group I: Durvalumab + zanzalintinib Experimental Treatment 2 Interventions

Participants will receive treatment regimen of durvalumab and zanzalintinib. Each treatment cycle is 28 days. Participants will continue to receive treatment until disease progression, death, or other reasons for withdrawal.

Who Is Running the Clinical Trial?

Amit Mahipal

Lead Sponsor

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07226063

Maintenance Zanzalintinib and Durvalumab in Participants ... The purpose of this study is to find out if taking zanzalintinib with durvalumab will improve how long people with advanced liver cancer will live. Detailed ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS4216

Phase II trial of zanzalintinib (XL-092) in combination with ... A Phase II study (CHECKMATE 040) reported an impressive objective response rate (ORR) of 29% with the combination of ipilimumab/nivolumab and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11632046/

Efficacy and safety of durvalumab rechallenge in advanced ... This study provides the first, concrete evidence that durvalumab rechallenge is effective for HCC patients who are refractory to anti-PD-1 therapy.

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/556320

Zanzalintinib (XL-092) Plus Durvalumab and ... This study will investigate if modulating the tumor microenvironment with biologic agents like XL-092 will have synergistic effect when combined with ...

5. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2100070

Tremelimumab plus Durvalumab in Unresectable ... Conclusions. STRIDE significantly improved overall survival versus sorafenib. Durvalumab monotherapy was noninferior to sorafenib for patients ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07226063?locStr=United+States&country=United+States

Maintenance Zanzalintinib and Durvalumab in Participants ... Studies have shown that patients with advanced liver cancer who had tremelimumab and durvalumab may benefit from taking zanzalintinib while they are taking ...