A Study of EBC-129 in Advanced Solid Tumours

A Phase 1A/B Study To Evaluate The Safety And Tolerability Of EBC-129 As A Single Agent And In Combination With Pembrolizumab In Advanced Solid Tumours

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

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumours
• Intervention / Treatment: Drug: Pembrolizumab; Drug: EBC-129

Detailed Description

This study is a prospective, open label study which is divided into 3 parts.

Part A will be dose escalation segment to identify the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of EBC-129 monotherapy.

Part B will be dose escalation segment to identify the MTD and RP2D of EBC-129 in combination with pembrolizumab.

Part C (dose expansion cohort) will be performed in an expanded cohort of patients with advanced solid malignancies at the RP2D of EBC-129 as a monotherapy identified in the dose escalation segment, Part A.

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Venkateshan Srirangam Prativadibhayankara, MD; Phone Number: +65 6407 4213; Email: Venkateshan_Srirangam@eddc.sg
• Study Contact Backup: Name: Veronica Diermayr; Phone Number: +65 6407 0706; Email: Veronica_Diermayr@eddc.sg

Study Locations

• Singapore
  • South West
    • Singapore, South West, Singapore, 168583
      • Recruiting
      • National Cancer Centre Singapore
      • Principal Investigator: Ng Matthew
    • Singapore, South West, Singapore, 119228
      • Recruiting
      • National University Hospital - Medical Oncology
      • Principal Investigator: Yong Wei Peng
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045-2517
      • Recruiting
      • University of Colorado Hospital (UCH) - University of Colorado Cancer Center (UCCC) - Neuroendocrine Tumor Center
      • Principal Investigator: Lentz Robert
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • UT MD Anderson Cancer Center
      • Principal Investigator: Meric-Bernstam Funda

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients ≥18 years (US) or ≥21 years (Singapore) old
2. Body weight within ≥40 kg - ≤100 kg during Parts A and B, and ≤120 kg during all other parts of the study
3. Demonstrated progression of a locally advanced unresectable or metastatic solid tumour with no alternative standard-of-care therapeutic option with a proven clinical benefit, or are intolerant to these therapies
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
5. Hepatic function and adequate renal function, as per protocol standard
6. Adequate bone marrow function as per protocol standard

Exclusion Criteria:

1. Unable or not willing to provide tumour tissue sample (from archival tissue or de-novo biopsy) unless if there is a significant risk for the patient to undergo biopsy
2. Has received investigational or anti-cancer therapy within 4 weeks (28 days) prior to starting study drug
3. Is receiving any concomitant anti-cancer therapy
4. Known severe hypersensitivity to E coli-derived products or filgrastim or peg-filgrastim and have significant allergies to such biological products
5. Has clinically active brain metastases
6. Has received prior radiation therapy
7. Has received prophylactic administration of haematopoietic colony stimulating factors within 4 weeks (28 days) prior to starting study drug
8. Patients concurrently using any strong P-glycoprotein (P-gp) inducers/inhibitors or strong cytochrome P3A (CYP3A) inhibitors within 14 days prior to the first dose of study drug or patients that use restricted or prohibited medications listed in the concomitant and other treatments section of the protocol
9. Pregnancy or breast feeding

10. For patients receiving pembrolizumab:

    1. Has an active autoimmune disease that has required systemic treatment in the past 2 years
    2. Patients who, according to the currently approved Keytruda (pembrolizumab) US package insert (USPI)/summary of product characteristics, had an immune-related adverse event (irAE) for which permanent discontinuation is mandated (any Grade 4 event and Grade 3 events of pneumonitis, hepatitis, and nephritis). Also, patients without formal contraindication due to previous irAE with any immune checkpoint inhibitor (approved or investigational) are not eligible if the AE has not resolved to grade 1 or better and/or still requires steroids (>10 mg of prednisone equivalent per day) for ongoing management.
    3. Patients with a history of pneumonitis/interstitial lung disease, patients who received live vaccines within 30 days of enrolment, and patients who discontinued prior immune checkpoint inhibitors due to Grade 2 myocarditis are excluded from enrolment into pembrolizumab-containing cohorts
11. Has had a major surgical procedure within 4 weeks (28 days) from starting the study drug
12. Patients with active or chronic corneal disorders, with other active ocular conditions requiring ongoing therapy or with any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy
13. Active infection including HIV, Hepatitis B or Hepatitis C

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A-Cohort 1; Patients will be administered Dose 1 of EBC-129 as a monotherapy.	Drug: EBC-129; EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-120-minute intravenous (IV) fusion.
Experimental: Part A-Cohort 2; Patients will be administered Dose 2 of EBC-129 as a monotherapy.	Drug: EBC-129; EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-120-minute intravenous (IV) fusion.
Experimental: Part A-Cohort 3; Patients will be administered Dose 3 of EBC-129 as a monotherapy.	Drug: EBC-129; EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-120-minute intravenous (IV) fusion.
Experimental: Part A-Cohort 4; Patients will be administered Dose 4 of EBC-129 as a monotherapy.	Drug: EBC-129; EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-120-minute intravenous (IV) fusion.
Experimental: Part A-Cohort 5; Patients will be administered Dose 5 of EBC-129 as a monotherapy.	Drug: EBC-129; EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-120-minute intravenous (IV) fusion.
Experimental: Part B; Patients will be administered three different dose levels of EBC-129 in combination with a fixed dose of pembrolizumab.	Drug: Pembrolizumab; Pembrolizumab will be administered at the dose of 200 mg IV every 21 days.; Drug: EBC-129; EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-120-minute intravenous (IV) fusion.
Experimental: Part C; Patients will be administered the highest dose of EBC-129 as a monotherapy at the RP2D determined in Part A of the study.	Drug: EBC-129; EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-120-minute intravenous (IV) fusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A and Part B- Determination of Maximum tolerated dose (MTD)		Approximately 2 years
Part A and Part B- Determination of the Recommended Phase 2 dose (RP2D)		Approximately 2 years
Part A, Part B and Part C- Number of patients with serious adverse events (SAEs) and treatment emergent adverse events (TEAEs)		From pre-screening (≥28 days from planned date of treatment i.e. Day 1) until end of study (EOS i.e., 30 days from last dose). Approximately 2 years
Part C- Objective response rate (ORR)	The number (%) of patients with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by investigator.	Day 1 through 12 cycles (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A, Part B and Part C- Time to Progression (TTP)	The time from the date of the first dose until objective tumour progression.	Approximately 3.3 years
Part A, Part B and Part C- Overall Survival (OS)	The time from the date of the first dose until death due to any cause.	Approximately 3.3 years
Part A, Part B and Part C- Maximum plasma concentration at steady state (Cmax_ss)		Day 1 through 12 cycles (each cycle is 21 days)
Part A, Part B and Part C- Trough concentration (Ctrough,ss)		Day 1 through 12 cycles (each cycle is 21 days)
Part A, Part B and Part C- Area under the curve at steady state (AUC0-21d_ss)		Day 1 through 12 cycles (each cycle is 21 days)
Part A, Part B and Part C- Accumulation ratios		Day 1 through 12 cycles (each cycle is 21 days)
Part A, Part B and Part C- Number of patients with detectable Anti-drug antibodies (ADAs)		Day 1 through 12 cycles (each cycle is 21 days)
Part A, Part B and Part C- Number of patients with neutralising antibodies		Day 1 through 12 cycles (each cycle is 21 days)
Part A, Part B and Part C- Time to maximum plasma concentration (Tmax) of EBC-129		Day 1 through 12 cycles (each cycle is 21 days)
Part A, Part B and Part C- Half-life (t1/2) of EBC-129		Day 1 through 12 cycles (each cycle is 21 days)
Part B- Cmax of Pemrolizumab		Day 1 through 12 cycles (each cycle is 21 days)
Part B- Ctrough of Pemrolizumab		Day 1 through 12 cycles (each cycle is 21 days)
Part B- AUC0-21d of Pemrolizumab		Cycle 1 and 2 (each cycle is 21 days)
Part B- Tmax of Pemrolizumab		Day 1 through 12 cycles (each cycle is 21 days)
Part B- t1/2 of Pemrolizumab		Day 1 through 12 cycles (each cycle is 21 days)
Part A and Part B- ORR	The number (%) of patients with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by investigator.	Day 1 through 12 cycles (each cycle is 21 days)
Part A, Part B and Part C- Disease control rate (DCR)	The percentage of patients who have a best overall response (BOR) of CR or PR in the first 12 weeks or who have demonstrated standard deviation (SD) for a minimum interval of 12 weeks following the start of treatment, will be determined based on RECIST.	Approximately 3.3 years
Part A, Part B and Part C- Duration of Response (DoR)	The time from the date of first documented response until the first date of documented progression or death in the absence of disease progression.	Approximately 3.3 years
Part A, Part B and Part C- Progression Free Survival (PFS)	The time from the date of first dose until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anti-cancer therapy prior to progression.	Approximately 3.3 years
Part A, Part B and Part C- Maximum Plasma Concentration (Cmax) of EBC-129		Cycle 1, 2, 3, and Cycle 4 (each cycle is 21 days)
Part A, Part B and Part C- Trough Concentration (Ctrough) of EBC-129		Cycle 1, 2, 3, and Cycle 4 (each cycle is 21 days)
Part A, Part B and Part C- Area under the plasma drug concentration-time curve from time zero to Day 21 post-dose (AUC0-21d) of EBC-129		Cycle 1 and Cycle 2 (each cycle is 21 days)
Part A- Comparison of tumour responses	The tumour responses (RECIST 1.1) will be compared between preselected patients and not pre-selected/not expressing the antigen when centrally assessed by immunohistochemistry (IHC).	Approximately 1.8 years

Collaborators and Investigators

• Sponsor: EDDC (Experimental Drug Development Centre), A*STAR Research Entities
• Collaborators: Parexel
• Investigators: Study Director: Venkateshan Srirangam Prativadibhayankara, MD, EDDC (Experimental Drug Development Centre), A*STAR Research Entities

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2023
• Primary Completion (Estimated): June 11, 2026
• Study Completion (Estimated): June 11, 2026

Study Registration Dates

• First Submitted: January 18, 2023
• First Submitted That Met QC Criteria: January 18, 2023
• First Posted (Actual): January 27, 2023

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Advanced solid tumours; Antibody drug conjugates (ADCs); Recommended phase-2 dose (RP2D); Monomethyl auristatin E (MMAE); N-glycosylated CEACAM5/6
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: EBC-129-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No