Pembrolizumab + Bavituximab for Liver Cancer

Overseen By Ellen Siglinsky

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: David Hsieh

Must be taking: Antivirals

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Heart disease, HIV, Autoimmune, 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

Compensation: Varies

Number of Visits: 3

Duration: 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, pembrolizumab (an immunotherapy drug) and bavituximab (an experimental treatment), to evaluate their effectiveness in treating liver cancer that has spread or cannot be removed by surgery. It targets patients with hepatocellular carcinoma (HCC) who have not received previous treatments for advanced stages. Suitable candidates are those with liver cancer that has spread or is inoperable and who have not tried similar treatments. As a Phase 2 trial, this research measures 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 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. If you are taking corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the study.

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

Research has shown that the combination of pembrolizumab and bavituximab has been tested for safety in people with advanced liver cancer. In one study, most patients tolerated this treatment well. Some reported side effects, such as fatigue or rash, were manageable and similar to those typically seen with pembrolizumab. No new safety issues emerged, suggesting the treatment is fairly safe based on current information. However, discussing potential risks with a healthcare provider before joining a clinical trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Pembrolizumab and Bavituximab for liver cancer because it offers a novel approach compared to existing treatments. Most current therapies focus on directly attacking cancer cells or inhibiting blood supply to tumors. However, Pembrolizumab is an immune checkpoint inhibitor that enhances the body's immune response against cancer cells, while Bavituximab targets specific cellular pathways to disrupt tumor growth. This combination could potentially improve the effectiveness of liver cancer treatment by harnessing the immune system in a unique way, offering hope for better outcomes where traditional treatments may fall short.

What evidence suggests that pembrolizumab and bavituximab could be effective for liver cancer?

Studies have shown that using pembrolizumab and bavituximab together, as participants in this trial will receive, may help shrink liver tumors in some patients. One study found that the tumors continued to shrink for an average of 13.3 months. Bavituximab targets a specific molecule that can enhance the effectiveness of pembrolizumab, a type of immune therapy. This combination works well together without causing additional side effects. Research suggests this treatment could benefit people with liver cancer, especially hepatocellular carcinoma (HCC). ^{2 6 7 8 9}

Who Is on the Research Team?

David Hsieh, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

Adults with advanced liver cancer (Hepatocellular Carcinoma) that can't be treated with surgery or local therapies, and who haven't had systemic therapy for it. They should have a good level of liver function (Child-Pugh Score A), no recent heart issues, controlled hepatitis if present, and not be on certain medications like high-dose steroids. Women must test negative for pregnancy and all participants must agree to use contraception.

Inclusion Criteria

My cancer can be measured on scans and is at least 1 cm big.

My cancer has spread beyond its original location.

I am fully active or can carry out light work.

Exclusion Criteria

I haven't had major surgery in the last 2 weeks or still have side effects.

I have not had any bleeding in my stomach or intestines in the last 2 months.

I have active brain tumors causing symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and bavituximab until disease progression, unacceptable toxicity, or withdrawal

36 months

Pembrolizumab every 3 weeks, Bavituximab weekly

Safety Follow-up

A mandatory safety follow-up is conducted 30 days post the last dose

4 weeks

Survival Follow-up

Patients are monitored for survival every 3 months after treatment discontinuation

Until death or study termination

What Are the Treatments Tested in This Trial?

Interventions

• Bavituximab
• Pembrolizumab

Trial Overview The trial is testing the combination of two drugs: Pembrolizumab and Bavituximab in patients with advanced Hepatocellular Carcinoma. It's an open-label phase II study which means everyone gets the treatment and both the researchers and participants know what's being given.

How Is the Trial Designed?

Group I: Pembro + Bavi Experimental Treatment 2 Interventions

Pembrolizumab 200 mg IV every 3 weeks plus, Bavituximab 3mg/kg IV weekly

Who Is Running the Clinical Trial?

David Hsieh

Lead Sponsor

Trials

1

Recruited

40+

Muhammad Beg

Lead Sponsor

Trials

1

Recruited

40+

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. nature.com nature.com/articles/s41467-024-46542-y

The phosphatidylserine targeting antibody bavituximab ... These results suggest that targeting phosphatidylserine may lead to synergistic effects with PD-1 blockade without increasing toxicity rates.

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/97/NCT03519997/Prot_SAP_000.pdf

A Phase II Study of Pembrolizumab and Bavituximab in ... Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38467639/

The phosphatidylserine targeting antibody bavituximab ... These results suggest that targeting phosphatidylserine may lead to synergistic effects with PD-1 blockade without increasing toxicity rates.

4. utsouthwestern.edu utsouthwestern.edu/newsroom/articles/year-2024/may-combined-therapy-live-cancer.html

Combined therapy makes headway for liver cancer For responders, the two drugs continued to shrink their tumors for a median time of 13.3 months, and four patients were still responding to the ...

5. ascopost.com ascopost.com/news/may-2024/bavituximab-plus-pembrolizumab-for-patients-with-hepatocellular-carcinoma/

Bavituximab Plus Pembrolizumab for Patients With ... The findings demonstrate the potential benefits of augmenting immunotherapy for hepatocellular carcinoma and other types of cancers. Background.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10928173/

The phosphatidylserine targeting antibody bavituximab ... Here the authors report the results of a single-arm phase 2 trial of bavituximab in combination with pembrolizumab (anti-PD1) for patients with ...

7. onclive.com onclive.com/view/bavituximab-plus-pembrolizumab-elicits-responses-in-untreated-advanced-hcc

Bavituximab Plus Pembrolizumab Elicits Responses in ... The SD and PD rates were 18.2% and 72.7%, respectively. “Our newly reported clinical data in frontline liver cancer show a near doubling of ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)02373-5/pdf

939P Phase II study of pembrolizumab (pembro) and ... We assessed the safety and efficacy of intratumoral (IT) injection of OBP-301 in advanced hepatocellular carcinoma (HCC). Methods: Open-label, phase I dose ...

9. utswmed.org utswmed.org/cancer/cancer-answers/targeting-phosphatidylserine-to-boost-immunotherapy--activity/

Targeting Phosphatidylserine to Boost Immunotherapy ... Adding antibody-based therapeutics shows promise in the treatment of hepatocellular carcinoma. Read how the clinical trials are showing ...