A Study of EBC-129 in Advanced Solid Tumours

Experimental Drug Development Centre (EDDC)

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumours

Treatments: Drug: Pembrolizumab; Drug: EBC-129

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05701527

EBC-129-01

Details and patient eligibility

About

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

Full description

This study is a prospective, open label study which is divided into 4 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.

Part D (Dose Fractionation Cohort) will be performed in patients with advanced solid malignancies with cancer indications that have shown preliminary clinical activity in Part C.

Enrollment: 98 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 for Part A and 0-1 for Parts B, C and D
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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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98 participants in 8 patient groups

Part A-Cohort 1

Experimental group

Description:

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

Treatment:

Drug: EBC-129

Part A-Cohort 2

Experimental group

Description:

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

Treatment:

Drug: EBC-129

Part A-Cohort 3

Experimental group

Description:

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

Treatment:

Drug: EBC-129

Part A-Cohort 4

Experimental group

Description:

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

Treatment:

Drug: EBC-129

Part A-Cohort 5

Experimental group

Description:

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

Treatment:

Drug: EBC-129

Part B

Experimental group

Description:

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

Treatment:

Drug: EBC-129

Drug: Pembrolizumab

Part C

Experimental group

Description:

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

Treatment:

Drug: EBC-129

Part D: EBC-129

Experimental group

Description:

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

Treatment:

Drug: EBC-129