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

Trial Summary

What is the purpose of this trial?

This study will assess the safety and tolerability of EBC-129 as a single agent and in combination with pembrolizumab in patients with advanced solid tumours

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.

What data supports the effectiveness of the drug EBC-129 + Pembrolizumab for advanced cancer?

Pembrolizumab, a part of the treatment, has shown effectiveness in treating various cancers, including non-small cell lung cancer, by improving survival rates compared to traditional chemotherapy. ^{1 2 3 4 5}

Is the combination of EBC-129 and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been studied in various cancers and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and immune-related issues such as lung inflammation and liver problems. These side effects were observed in studies for different cancers, so it's important to discuss potential risks with your doctor. ^{2 6 7 8 9}

What makes the drug EBC-129 + Pembrolizumab unique for advanced cancer?

The combination of EBC-129 with Pembrolizumab is unique because Pembrolizumab is a PD-1 inhibitor that helps the immune system attack cancer cells, and it has shown effectiveness in various cancers. This combination may offer a novel approach by potentially enhancing the immune response against advanced cancers, although specific details about EBC-129's role are not provided in the available research. ^{1 2 5 7 10}

Research Team

Venkateshan Srirangam Prativadibhayankara, MD

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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 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 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 (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]

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]

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 (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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

3. Germany pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. [2020]

4. China 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. [2022]

5. China 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). [2023]

6. England pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Benefit of Pembrolizumab in Advanced Urothelial Cancer Patients in Real-Life Setting: An Efficacy and Safety Monocentric Study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]