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
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.
Arms & interventions
- DrugEBC-129
EBC-129 will be administered on Day 1 of each 21-Day cycle (Parts A, B, and C), and two doses starting from Day 1 for 21-day cycle and three doses starting from Day 1 for 28-day cycle (Part D) via a 30-120-minute intravenous (IV) fusion.
- DrugPembrolizumab
Pembrolizumab will be administered at the dose of 200 mg IV every 21 days.
Outcome measures
Primary
Part A, Part B, Part C and Part D- Number of patients with serious adverse events (SAEs) and treatment emergent adverse events (TEAEs)
Time frame: 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 A, Part B and Part D- Determination of Maximum tolerated dose (MTD)
Time frame: Approximately 2 years
Part A, Part B and Part D- Determination of the Recommended Phase 2 dose (RP2D)
Time frame: 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.
Time frame: Day 1 through 12 cycles (each cycle is 21 days)
Part D- ORR
The number (%) of patients with a best overall response of CR or PR per RECIST v1.1 as assessed by investigator.
Time frame: Day 1 through 12 cycles (each cycle is 21 or 28 days)
Secondary
Part A and Part B- ORR
Time frame: Day 1 through 12 cycles (each cycle is 21 days)
Part A, Part B, Part C and Part D- Disease control rate (DCR)
Time frame: Approximately 3.3 years
Part A, Part B, Part C and Part D- Duration of Response (DoR)
Time frame: Approximately 3.3 years
Part A, Part B, Part C and Part D- Time to Progression (TTP)
Time frame: Approximately 3.3 years
Part A, Part B, Part C and Part D- Progression Free Survival (PFS)
Time frame: Approximately 3.3 years
Part A, Part B, Part C and Part D- Overall Survival (OS)
Time frame: Approximately 3.3 years
Part A, Part B, Part C and Part D- Maximum Plasma Concentration (Cmax) of EBC-129
Time frame: 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)
Part A, Part B, Part C and Part D- Trough Concentration (Ctrough) of EBC-129
Time frame: 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)
Part A, Part B, Part C and Part D- Area under the curve (AUC) of EBC-129
Time frame: 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)
Part A, Part B, Part C and Part D- Maximum plasma concentration at steady state (Cmax_ss) of EBC-129
Time frame: 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)
Part A, Part B, Part C and Part D- Trough concentration at steady state (Ctrough,ss) of EBC-129
Time frame: 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)
Part A, Part B, Part C and Part D- Area under the curve at steady state (AUC_ss) of EBC-129
Time frame: 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)
Part A, Part B, Part C and Part D- Accumulation ratios of EBC-129
Time frame: 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)
Part A, Part B, Part C and Part D- Time to maximum plasma concentration (Tmax) of EBC-129
Time frame: 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)
Part A, Part B, Part C and Part D- Half-life (t1/2) of EBC-129
Time frame: 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)
Part B- Cmax of Pemrolizumab
Time frame: Day 1 through 12 cycles (each cycle is 21 days)
Part B- Ctrough of Pemrolizumab
Time frame: Day 1 through 12 cycles (each cycle is 21 days)
Part B- AUC of Pemrolizumab
Time frame: Cycle 1 and 2 (each cycle is 21 days)
Part B- Tmax of Pemrolizumab
Time frame: Day 1 through 12 cycles (each cycle is 21 days)
Part B- t1/2 of Pemrolizumab
Time frame: Day 1 through 12 cycles (each cycle is 21 days)
Part A, Part B, Part C and Part D- Number of patients with detectable Anti-drug antibodies (ADAs)
Time frame: 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)
Part A, Part B, Part C and Part D- Number of patients with neutralising antibodies
Time frame: 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)
Part A- Comparison of tumour responses
Time frame: Approximately 1.8 years
Eligibility criteria
Study locations (2)
University of Colorado Hospital (UCH) - University of Colorado Cancer Center (UCCC) - Neuroendocrine Tumor Center
Aurora, Colorado, 80045-2517
UT MD Anderson Cancer Center
Houston, Texas, 77030