EBC-129 + Pembrolizumab for Advanced Cancer

Recruiting at 4 trial locations

Overseen By Veronica Diermayr

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: EDDC (Experimental Drug Development Centre), A*STAR Research Entities

Must not be taking: P-gp inducers, CYP3A inhibitors

Disqualifiers: Brain metastases, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

95 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the safety of EBC-129, an experimental treatment, both alone and in combination with pembrolizumab, a cancer therapy, in individuals with advanced solid tumors unresponsive to other treatments. Participants will receive varying doses of EBC-129 to determine the most effective and tolerable dose. This trial may suit those with advanced cancer that cannot be surgically removed or has metastasized, and who have exhausted other treatment options. As a Phase 1 trial, this research focuses on understanding the treatment's effects in humans, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any investigational or anti-cancer therapy, strong P-glycoprotein (P-gp) inducers/inhibitors, and strong cytochrome P3A (CYP3A) inhibitors at least 14 days before starting the study drug. If you are on any restricted or prohibited medications, you may need to stop those as well.

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

Research has shown that EBC-129 has a manageable safety profile based on previous studies. Among the 58 patients treated so far, the most common side effects were mild, such as low white blood cell counts (neutropenia) and infusion-related reactions. These side effects were straightforward to manage, suggesting that EBC-129 is generally well-tolerated.

Pembrolizumab is an FDA-approved treatment for advanced melanoma. Studies have demonstrated its effectiveness and well-known safety profile, meaning doctors understand its usual side effects and how to manage them.

The combination of EBC-129 with pembrolizumab remains under study, but early results are promising. The safety data for EBC-129 and pembrolizumab individually provide a good starting point for understanding what to expect. However, the safety of the combination is still being evaluated, so close monitoring is essential. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about EBC-129 and pembrolizumab for advanced cancer because EBC-129 brings a novel approach to treatment. Unlike standard cancer therapies that often target tumors broadly, EBC-129 is designed to act on specific molecular targets, potentially improving effectiveness and reducing side effects. In combination with pembrolizumab, an immunotherapy that boosts the body's natural defenses to fight cancer, this treatment could offer a more personalized and potent attack on cancer cells. This unique pairing might enhance the immune response against tumors, providing new hope for patients with advanced cancer.

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

Research has shown that EBC-129, one of the treatments in this trial, holds promise for patients with pancreatic cancer, which is often difficult to treat. In earlier studies, patients responded well, and their cancer progression slowed. This suggests that EBC-129 might help slow cancer growth.

In this trial, some participants will receive EBC-129 alone, while others will receive it with pembrolizumab. Pembrolizumab, already proven to extend life in people with various cancers like lung cancer, is being tested with EBC-129 to determine if they work better together against advanced cancers. Early signs suggest this combination could effectively treat challenging cancers. ^{4 6 7 8 9}

Who Is on the Research Team?

Venkateshan Srirangam Prativadibhayankara, MD

Principal Investigator

EDDC (Experimental Drug Development Centre), A*STAR Research Entities

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that have grown despite no available treatments or intolerance to them can join. They must be over 18 (USA) or 21 (Singapore), weigh between 40-100 kg, and have a performance status of ≤2. Participants need proper bone marrow, liver, and kidney function but cannot join if they've had recent cancer therapy, severe allergies to E coli-derived products, active brain metastases, certain infections like HIV/Hepatitis B/C, autoimmune diseases treated within the last two years, are pregnant/breastfeeding or have specific eye conditions.

Inclusion Criteria

My bone marrow is working well.

My weight is between 40 kg and 100 kg.

My cancer has spread, cannot be surgically removed, and I can't use or have used all standard treatments without success.

Exclusion Criteria

I have active brain tumors from cancer spread.

I have undergone radiation therapy before.

I have received drugs to boost my blood cells within the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part A)

Dose escalation to identify the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of EBC-129 monotherapy

Approximately 12 weeks

Dose Escalation (Part B)

Dose escalation to identify the MTD and RP2D of EBC-129 in combination with pembrolizumab

Approximately 12 weeks

Dose Expansion (Part C)

Dose expansion cohort with EBC-129 monotherapy at the RP2D identified in Part A

Approximately 12 weeks

Dose Fractionation (Part D)

Dose fractionation cohort with EBC-129 monotherapy in patients with cancer indications showing preliminary clinical activity

Approximately 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 3.3 years

What Are the Treatments Tested in This Trial?

Interventions

• EBC-129
• Pembrolizumab

Trial Overview

The trial is testing EBC-129 alone and combined with pembrolizumab for safety in treating advanced solid tumors. It will see how patients tolerate these drugs and look for any signs of effectiveness against the tumors.

How Is the Trial Designed?

Group I: Part D: EBC-129 Experimental Treatment 1 Intervention

Patients will be administered EBC-129 as a monotherapy as per two-dose or three-dose per cycle regimen.

Group II: Part C Experimental Treatment 1 Intervention

Patients will be administered the highest dose of EBC-129 as a monotherapy at the RP2D determined in Part A of the study.

Group III: Part B Experimental Treatment 2 Interventions

Patients will be administered three different dose levels of EBC-129 in combination with a fixed dose of pembrolizumab.

Group IV: Part A-Cohort 5 Experimental Treatment 1 Intervention

Patients will be administered Dose 5 of EBC-129 as a monotherapy.

Group V: Part A-Cohort 4 Experimental Treatment 1 Intervention

Patients will be administered Dose 4 of EBC-129 as a monotherapy.

Group VI: Part A-Cohort 3 Experimental Treatment 1 Intervention

Patients will be administered Dose 3 of EBC-129 as a monotherapy.

Group VII: Part A-Cohort 2 Experimental Treatment 1 Intervention

Patients will be administered Dose 2 of EBC-129 as a monotherapy.

Group VIII: Part A-Cohort 1 Experimental Treatment 1 Intervention

Patients will be administered Dose 1 of EBC-129 as a monotherapy.

EBC-129 is already approved in United States for the following indications:

Approved in United States as EBC-129 for:

• Advanced solid tumours

Who Is Running the Clinical Trial?

EDDC (Experimental Drug Development Centre), A*STAR Research Entities

Lead Sponsor

Trials

4

Recruited

190+

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

In a study of 78 patients with advanced urothelial carcinoma treated with pembrolizumab, the median overall survival was 7.3 months, and the estimated survival rate at 6 months was 61.5%, indicating its efficacy in a real-life setting.

The treatment was generally well-tolerated, with the most common side effects being fatigue and gastrointestinal issues, but no severe adverse events occurred in more than 5% of patients, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Benefit of Pembrolizumab in Advanced Urothelial Cancer Patients in Real-Life Setting: An Efficacy and Safety Monocentric Study. Dang, E., Vallée, A., Lepage-Seydoux, C., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung carcinoma, has been associated with improved overall survival compared to traditional chemotherapy, but it can also lead to serious side effects.

This case report highlights a rare but critical complication: a 62-year-old man experienced small intestinal perforation due to metastatic lung adenocarcinoma after receiving pembrolizumab, emphasizing the need for careful monitoring of patients for potential autoimmune side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. Sato, S., Senmaru, N., Ishido, K., et al.[2020]

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

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EBC-129 + Pembrolizumab for Advanced Cancer

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