Sorafenib + Pembrolizumab for Liver Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Roswell Park Cancer Institute

Must not be taking: Warfarin, Heparin, Retrovirals, others

Disqualifiers: HIV, Autoimmune disease, Brain metastases, 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: 33

Duration: Up to 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of two treatments, sorafenib tosylate and pembrolizumab, to assess their effectiveness in treating metastatic liver cancer. Sorafenib tosylate may inhibit cancer cell growth by blocking certain enzymes, while pembrolizumab (KEYTRUDA) aims to help the immune system combat cancer cells. The trial seeks to determine if these treatments together offer greater effectiveness for patients with advanced liver cancer. Suitable candidates for this trial have metastatic liver cancer and have experienced disease progression despite prior treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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

The trial information does not specify if you need to stop taking your current medications. However, if you are on antiviral therapy for hepatitis B, you should continue it during the study. It's best to discuss your specific medications with the study team.

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

Research has shown that pembrolizumab, a monoclonal antibody, is generally safe for individuals with advanced liver cancer. In the KEYNOTE-224 study, pembrolizumab proved safe for patients who had previously tried other treatments. Sorafenib, already approved for liver cancer, has established safety information. Although both medicines can cause side effects, most people find them manageable. This trial examines how well these two treatments work together, making it crucial to carefully assess their combined effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of sorafenib and pembrolizumab for liver cancer because it brings a fresh approach to treatment. Unlike traditional therapies that might solely target tumor growth, sorafenib works by blocking certain proteins that help cancer cells grow, while pembrolizumab is an immunotherapy that boosts the body's own ability to fight cancer by targeting the PD-1 pathway. This dual action not only aims to halt cancer progression but also enhances the immune system's response, offering a potential new avenue for patients who may not respond to existing treatments.

What evidence suggests that sorafenib tosylate and pembrolizumab might be effective for liver cancer?

Research has shown that using sorafenib and pembrolizumab together may help treat liver cancer that has spread. Sorafenib blocks certain proteins that aid cancer cell growth, while pembrolizumab, a type of targeted therapy, helps prevent cancer cells from spreading. The KEYNOTE-224 trial found that pembrolizumab alone was effective and manageable for patients with advanced liver cancer. In this trial, participants will receive a combination of sorafenib and pembrolizumab to better stop the cancer from growing and spreading. Early studies suggest this combination might lead to improved outcomes for liver cancer patients. ^{2 5 6 7 8}

Who Is on the Research Team?

Renuka Iyer

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic liver cancer who have not had prior treatments with sorafenib or PD1 blockers. They must have good physical function, adequate blood counts, and controlled hepatitis if present. Pregnant women, those with HIV, recent chemotherapy or radiotherapy recipients, and individuals with certain heart conditions cannot participate.

Inclusion Criteria

I have hepatitis B, but it is under control.

Total bilirubin =< 2.0 mg/dL

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 X ULN

Exclusion Criteria

I do not have brain metastases.

I am currently pregnant or breastfeeding.

I've had one treatment for my condition, but not with sorafenib or PD1 blockers.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sorafenib tosylate orally twice daily and pembrolizumab intravenously every 3 weeks

Up to 6 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

30 days post-treatment, then every 3 months for 1 year, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Sorafenib Tosylate

Trial Overview The study is testing the combination of Sorafenib Tosylate (a drug that blocks tumor growth enzymes) and Pembrolizumab (an antibody that may prevent tumor cells from growing) to see if they are more effective together in treating liver cancer than when used separately.

How Is the Trial Designed?

Group I: Treatment (sorafenib tosylate, pembrolizumab) Experimental Treatment 3 Interventions

Patients receive sorafenib tosylate PO BID on days -28 to -1 and 1-21. Patients also receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9784157/

Data from the Open-Label, Phase II KEYNOTE-224 Trial - PMC KEYNOTE-224 cohort 1 demonstrated that pembrolizumab was efficacious and tolerable in patients with advanced hepatocellular carcinoma (HCC) previously treated ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2949713225000515

Meta-analysis Relative treatment effects of first-line ... Progression-free survival between chemotherapy and immunotherapy treatment for hepatocellular carcinoma. The data in Table 3 show the ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04152356

Combined Immunotherapy and Targeted Therapy for ... Patients with hepatocellular carcinoma (HCC) often undergo liver cancer resection, but the recurrence rate can reach 70% to 100%, which seriously affects the ...

4. spandidos-publications.com spandidos-publications.com/10.3892/ol.2021.12540

Clinical outcomes and influencing factors of PD‑1/PD‑L1 in ... The present review discusses the clinical results and influencing factors of PD‐1/PD‐L1 inhibitors in HCC to provide insight into the development and ...

5. withpower.com withpower.com/trial/phase-2-carcinoma-hepatocellular-11-2017-a5d28

Sorafenib + Pembrolizumab for Liver Cancer Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03211416

Sorafenib Tosylate and Pembrolizumab in Treating ... This phase Ib/II trial studies how well sorafenib tosylate and pembrolizumab work in treating patients with liver cancer that has spread to other parts of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7905537/

Clinical outcomes and influencing factors of PD-1/PD-L1 in ... Hepatocellular carcinoma (HCC) has an increasing incidence worldwide, and the global 5-year survival rate ranges from 5–30%.

8. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2810119

Tislelizumab vs Sorafenib as First-Line Treatment for ... Tislelizumab demonstrated overall survival noninferiority compared with sorafenib, with numerically higher and more durable objective responses than sorafenib.