Clinical trial NCT05701527: A Study of EBC-129 in Advanced Solid Tumours
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumours
Keywords: Advanced solid tumours
Antibody drug conjugates (ADCs)
Recommended phase-2 dose (RP2D)
Monomethyl auristatin E (MMAE)
N-glycosylated CEACAM5/6
Lead sponsor: EDDC (Experimental Drug Development Centre), A*STAR Research Entities
Sponsor class: OTHER_GOV
Collaborators: name: Parexel
First posted: 2023-01-27
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Part A, Part B, Part C and Part D- Number of patients with serious adverse events (SAEs) and treatment emergent adverse events (TEAEs)
timeFrame: 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
measure: Part A, Part B and Part D- Determination of Maximum tolerated dose (MTD)
timeFrame: Approximately 2 years
measure: Part A, Part B and Part D- Determination of the Recommended Phase 2 dose (RP2D)
timeFrame: Approximately 2 years
measure: Part C- Objective response rate (ORR)
timeFrame: Day 1 through 12 cycles (each cycle is 21 days)
measure: Part D- ORR
timeFrame: Day 1 through 12 cycles (each cycle is 21 or 28 days)
Secondary outcomes:
measure: Part A and Part B- ORR
timeFrame: Day 1 through 12 cycles (each cycle is 21 days)
measure: Part A, Part B, Part C and Part D- Disease control rate (DCR)
timeFrame: Approximately 3.3 years
measure: Part A, Part B, Part C and Part D- Duration of Response (DoR)
timeFrame: Approximately 3.3 years
measure: Part A, Part B, Part C and Part D- Time to Progression (TTP)
timeFrame: Approximately 3.3 years
measure: Part A, Part B, Part C and Part D- Progression Free Survival (PFS)
timeFrame: Approximately 3.3 years
measure: Part A, Part B, Part C and Part D- Overall Survival (OS)
timeFrame: Approximately 3.3 years
measure: Part A, Part B, Part C and Part D- Maximum Plasma Concentration (Cmax) of EBC-129
timeFrame: Parts A, B and C: Cycle 1, 2, 3, and Cycle 4 (each cycle is 21 days); Part D: Cycle 1 (each cycle is 21 or 28 days)
measure: Part A, Part B, Part C and Part D- Trough Concentration (Ctrough) of EBC-129
timeFrame: Parts A, B and C: Cycle 1, 2, 3, and Cycle 4 (each cycle is 21 days); Part D: Cycle 1 (each cycle is 21 or 28 days)
measure: Part A, Part B, Part C and Part D- Area under the curve (AUC) of EBC-129
timeFrame: Parts A, B, and C: Cycle 1 and Cycle 2 (each cycle is 21 days); Part D: Cycle 1 (each cycle is 21 or 28 days)
measure: Part A, Part B, Part C and Part D- Maximum plasma concentration at steady state (Cmax_ss) of EBC-129
timeFrame: Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days)
measure: Part A, Part B, Part C and Part D- Trough concentration at steady state (Ctrough,ss) of EBC-129
timeFrame: Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days)
measure: Part A, Part B, Part C and Part D- Area under the curve at steady state (AUC_ss) of EBC-129
timeFrame: Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days)
measure: Part A, Part B, Part C and Part D- Accumulation ratios of EBC-129
timeFrame: Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days)
measure: Part A, Part B, Part C and Part D- Time to maximum plasma concentration (Tmax) of EBC-129
timeFrame: Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days)
measure: Part A, Part B, Part C and Part D- Half-life (t1/2) of EBC-129
timeFrame: Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days)
measure: Part B- Cmax of Pemrolizumab
timeFrame: Day 1 through 12 cycles (each cycle is 21 days)
measure: Part B- Ctrough of Pemrolizumab
timeFrame: Day 1 through 12 cycles (each cycle is 21 days)
measure: Part B- AUC of Pemrolizumab
timeFrame: Cycle 1 and 2 (each cycle is 21 days)
measure: Part B- Tmax of Pemrolizumab
timeFrame: Day 1 through 12 cycles (each cycle is 21 days)
measure: Part B- t1/2 of Pemrolizumab
timeFrame: Day 1 through 12 cycles (each cycle is 21 days)
measure: Part A, Part B, Part C and Part D- Number of patients with detectable Anti-drug antibodies (ADAs)
timeFrame: Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days)
measure: Part A, Part B, Part C and Part D- Number of patients with neutralising antibodies
timeFrame: Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days)
measure: Part A- Comparison of tumour responses
timeFrame: Approximately 1.8 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital (UCH) - University of Colorado Cancer Center (UCCC) - Neuroendocrine Tumor Center
state: Colorado
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
city: Singapore
country: Singapore
facility: National University Hospital - Medical Oncology
state: South West
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
state: South West
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: EDDC (Experimental Drug Development Centre), A*STAR Research Entities
name: Venkateshan Srirangam Prativadibhayankara, MD
role: STUDY_DIRECTOR
References: