sEphB4-HSA + Pembrolizumab for Cancer

Not currently recruiting at 8 trial locations

Overseen By Cheryl Kefauver, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Southern California

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Active TB, CNS metastases, others

Stay on Your Current Meds You can continue your current medications while participating

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: 9

Duration: Varies, courses repeat every 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for certain types of cancer. It pairs a fusion protein, which blocks specific cancer cell interactions, with pembrolizumab (also known as KEYTRUDA), a drug that helps the immune system fight cancer. The trial divides participants into four groups, focusing on different stages and types of urothelial and prostate cancers. Individuals with advanced urothelial cancer resistant to platinum-based treatments or those with locally advanced prostate cancer might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on systemic steroid therapy or any form of immunosuppressive therapy within 7 days before the trial starts. It's best to discuss your specific medications with the trial team.

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

Research has shown that pembrolizumab, also known as KEYTRUDA, is generally well-tolerated. In a large study involving over 8,900 patients, pembrolizumab was administered for up to 59 doses, and most patients managed the treatment well. Common side effects included tiredness, skin rash, and itching, but these were usually manageable.

For sEphB4-HSA, less information is available. However, its progression to Phase 2 trials indicates that earlier tests demonstrated sufficient safety to warrant further study in more patients. This suggests that serious issues likely did not appear in earlier, smaller studies.

Overall, the combination treatment of sEphB4-HSA and pembrolizumab is being tested for safety and effectiveness in treating certain types of cancer. While pembrolizumab has a known safety record, researchers continue to gather more data about sEphB4-HSA. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab and the recombinant EphB4-HSA fusion protein because it offers a fresh approach to cancer treatment. Unlike standard therapies that often focus on inhibiting cancer cell growth or killing cells directly, this combination works by enhancing the immune system's ability to recognize and attack cancer cells. Pembrolizumab is an immune checkpoint inhibitor that unleashes the body's T-cells, and the EphB4-HSA fusion protein targets specific pathways involved in tumor growth and blood supply. By bringing these two mechanisms together, this treatment could offer more effective cancer management with potentially fewer side effects compared to conventional options.

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

In this trial, participants will receive a combination of pembrolizumab and the recombinant EphB4-HSA fusion protein. Research has shown that pembrolizumab, a medicine that aids the immune system, improves survival rates in various cancers. Specifically, studies on advanced non-small cell lung cancer demonstrated that it increased the five-year survival rate to about 19-22% when combined with chemotherapy, suggesting it could help patients fight cancer more effectively.

The recombinant EphB4-HSA fusion protein is designed to block proteins that promote tumor growth. Although less information exists about this treatment in humans, its mechanism suggests effectiveness when used with pembrolizumab. Together, these treatments aim to enhance the immune system's ability to attack cancer cells. ^{6 7 8 9 10}

Who Is on the Research Team?

Sarmad Sadeghi, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors, specifically metastatic or recurrent urothelial carcinoma that's resistant to platinum-based treatment, and locally advanced prostate cancer. Participants must have adequate organ function, no recent other treatments or surgeries, and agree to use contraception. Those with active pneumonitis, uncontrolled hypertension, known psychiatric disorders affecting cooperation, prior anti-PD-1/PD-L1 therapy or sEphB4-HSA are excluded.

Inclusion Criteria

I have prostate cancer with a Gleason Score of 7 or higher and PSA over 4.0, suitable for surgery.

My bladder cancer is at a stage where surgery to remove it is planned and considered potentially curative.

My liver function tests are within the required range.

Exclusion Criteria

I haven't had cancer treatment with a monoclonal antibody in the last 4 weeks or have recovered from its side effects.

I have been diagnosed with HIV.

Your blood pressure is too high and not under control, with readings above 140/90 mmHg. If your blood pressure appears high only in the doctor's office, you may still be considered eligible if your blood pressure readings at home are within the acceptable range. However, this decision will depend on the Sponsor's review and agreement.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive recombinant EphB4-HSA fusion protein IV over 60 minutes on days 1, 8, and 15 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Varies, courses repeat every 3 weeks

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 30 days and then every 6-12 weeks.

Up to 3 years

Follow-up visits every 6-12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Recombinant EphB4-HSA Fusion Protein

Trial Overview The trial tests a combination of sEphB4-HSA (a fusion protein blocking cell surface receptors) and Pembrolizumab (an anti-PD1 antibody) on four cohorts: two for second and third-line treatment of urothelial carcinoma after platinum failure; one as neoadjuvant for muscle invasive urothelial carcinoma; another as neoadjuvant for prostate cancer.

How Is the Trial Designed?

Group I: Treatment (EphB4-HSA and pembrolizumab) Experimental Treatment 5 Interventions

Patients receive recombinant EphB4-HSA fusion protein IV over 60 minutes on days 1, 8, and 15 and 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?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

The first-in-human study of MK-4830, a novel IgG4 monoclonal antibody targeting the ILT4 receptor, showed it was well tolerated with no dose-limiting toxicities among 84 patients with advanced solid tumors.

In combination with pembrolizumab, MK-4830 demonstrated promising antitumor activity, with 11 out of 34 patients achieving objective responses, including some who had previously progressed on other therapies, suggesting enhanced effectiveness in certain tumor microenvironments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Class Anti-immunoglobulin-like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance Mechanism in Patients with Advanced Solid Tumors. Siu, LL., Wang, D., Hilton, J., et al.[2023]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

In a review of 567 reports of immune-mediated necrotizing myopathy (IMNM), 14 cases were associated with pembrolizumab, indicating a significant link between this treatment and the adverse event, with a reporting odds ratio of 17.59.

The study emphasizes the importance of updated diagnostic criteria for IMNM and suggests that better collaboration between oncologists and neurologists is needed to address these neurological complications related to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-mediated necrotizing myopathy with pembrolizumab: a specific neuromuscular entity. Trenque, T., Lepoix, E., Trenque, A., et al.[2022]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Citations

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Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10082298/

Five-Year Outcomes With Pembrolizumab Versus ... With 5-year OS rates of up to 22%, these data support the continued use of pembrolizumab monotherapy as a standard-of-care treatment for previously untreated PD ...

3. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%). In KEYNOTE⁠-⁠671, adverse reactions ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

5. nature.com nature.com/articles/s41416-024-02895-1

Real-world evidence for pembrolizumab in non-small cell ... Our nationwide study demonstrated a survival benefit over conventional chemotherapy of a similar magnitude as observed in clinical trials.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11227881/

Safety profile of pembrolizumab monotherapy based on an ... Results: Safety data from 8937 patients in 31 trials of pembrolizumab monotherapy were pooled (median, seven administrations; range, 1–59). Median duration ...

7. merck.com merck.com/news/ten-year-data-for-mercks-keytruda-pembrolizumab-demonstrates-sustained-overall-survival-benefit-versus-ipilimumab-in-advanced-melanoma/

Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ... At 10 years, more than one-third (34.0%) of patients with advanced melanoma were alive after treatment with KEYTRUDA, compared to 23.6% of patients treated ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11117617/

A Systematic Review and Meta-Analysis Pembrolizumab demonstrated antitumor activity and was well tolerated in patients with PD-L1-positive advanced cervical cancer, consistent with safety profiles ...

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02885

Five-Year Outcomes With Pembrolizumab Versus ... The estimated 5-year OS rates were 11.9% and 7.4% in the pembrolizumab and chemotherapy groups, respectively (Data Supplement). Safety. In the ...