A Study of EBC-129 in Advanced Solid Tumours

Study Overview
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Brief Summary
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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
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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 subjects with advanced solid malignancies at the RP2D of EBC-129 as a monotherapy identified in the dose escalation segment, Part A.

Official Title
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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

Conditions
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Advanced Solid Tumours

Intervention / Treatment
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* Drug: EBC-129
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects ≥18 years (USA) or ≥21 years (Singapore) old Body weight within ≥40 kg - ≤100 kg 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 Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 Hepatic function and adequate renal function, as per protocol standard Adequate bone marrow function as per protocol standard Exclusion Criteria: 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 Has received investigational or anti-cancer therapy within 4 weeks (28 days) prior to starting study drug Is receiving any concomitant anti-cancer therapy Known severe hypersensitivity to E coli-derived products or previously received filgrastim or peg-filgrastim and have significant allergies to such biological products Has clinically active brain metastases Has received prior radiation therapy Has received prophylactic administration of haematopoietic colony stimulating factors within 4 weeks (28 days) prior to starting study drug Patients concurrently using any strong P-glycoprotein (P-gp) inducers/inhibitors or strong CYP3A inhibitors within 14 days prior to the first dose of study drug or subjects that use restricted or prohibited medications listed in the concomitant and other treatments section of the protocol Pregnancy or breast feeding For patients receiving pembrolizumab: Has an active autoimmune disease that has required systemic treatment in the past 2 years Patients who, according to the currently approved Keytruda (pembrolizumab) USPI/SmPC, 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, subjects 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 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 Has had a major surgical procedure within 4 weeks (28 days) from starting the study drug 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 Active infection including HIV, Hepatitis B or Hepatitis C

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A-Cohort 1<br>Patients will be administered Dose 1 of EBC-129 as a monotherapy. | Drug: EBC-129<br>* EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-90-minute intravenous (IV) fusion.<br>|
| Experimental: Part A-Cohort 2<br>Patients will be administered Dose 2 of EBC-129 as a monotherapy. | Drug: EBC-129<br>* EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-90-minute intravenous (IV) fusion.<br>|
| Experimental: Part A-Cohort 3<br>Patients will be administered Dose 3 of EBC-129 as a monotherapy. | Drug: EBC-129<br>* EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-90-minute intravenous (IV) fusion.<br>|
| Experimental: Part A-Cohort 4<br>Patients will be administered Dose 4 of EBC-129 as a monotherapy. | Drug: EBC-129<br>* EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-90-minute intravenous (IV) fusion.<br>|
| Experimental: Part A-Cohort 5<br>Patients will be administered Dose 5 of EBC-129 as a monotherapy. | Drug: EBC-129<br>* EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-90-minute intravenous (IV) fusion.<br>|
| Experimental: Part B<br>Patients will be administered three different dose levels of EBC-129 in combination with a fixed dose of pembrolizumab. | Drug: EBC-129<br>* EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-90-minute intravenous (IV) fusion.<br>Drug: Pembrolizumab<br>* Pembrolizumab will be administered at the dose of 200 mg IV every 21 days.<br>|
| Experimental: Part C<br>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<br>* EBC-129 will be administered on Day 1 of each 21-Day cycle via a 30-90-minute intravenous (IV) fusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A, Part B and Part C- Number of patients with serious adverse events (SAEs) and treatment emergent adverse events (TEAEs) |  | From screening (-28 days to -1 day) until end of study (EOS i.e., 30 days from last dose). Approximately 2 years | 
| 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 C- Objective response rate (ORR) | The number (%) of subjects with a best overall response of confirmed complete response (CR) or partial response (PR) per RECIST v1.1 criteria measured by CT or MRI. | Day 1 through 12 cycles (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A and Part B- ORR | The number (%) of subjects with a best overall response of confirmed 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 subjects 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 (which is subsequently confirmed) 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- 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- 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 subject withdraws from therapy or receives another anti-cancer therapy prior to 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 (Cmax) of EBC-129 |  | Cycle 2, 3, and Cycle 4 (each cycle is 21 days) | 
| Part A, Part B and Part C- Trough Concentration (Ctrough) of EBC-129 |  | Cycle 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 (each cycle is 21 days) | 
| 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- 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, 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- Comparison of tumour responses | The tumour responses (RECIST 1.1) will be compared between preselected subjects and not pre-selected/not expressing the antigen when centrally assessed by immunohistochemistry (IHC). | Approximately 1.8 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced solid tumours, Antibody drug conjugates (ADCs), Recommended phase-2 dose (RP2D), Monomethyl auristatin E (MMAE), N-glycosylated CEACAM5/6