This is an open-label, multicenter, Phase Ib trial designed to evaluate the safety, tolerability, and preliminary efficacy of EMB-01 in combination with chemotherapy in patients with unresectable or metastatic colorectal cancer (CRC), and to determine the recommended Phase II combination dose (RP2CD). The study consists of a dose escalation phase followed by a dose expansion phase. Approximately 30 patients are planned to be enrolled in each combination treatment group across both phases, with a maximum total enrollment of approximately 120 patients.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
EMB-01 is a bispecific antibody against epidermal growth factor receptor (EGFR) and the receptor tyrosine kinase Met (cMET).
Irinotecan will be administered as intravenous infusion.
TAS-102 will be administered orally.
mFOLFOX6 will be administered as intravenous infusion.
FOLFIRI will be administered as intravenous infusion.
Incidence and severity of adverse events (AEs)
Safety profile of EMB-01 in combination with chemotherapy will be evaluated by the incidence, severity, seriousness, and relationship of AEs, graded per CTCAE v5.0
Time frame: From enrollment up to 30 days after last dose of study treatment
Incidence of dose-limiting toxicities (DLTs)
DLTs will be assessed according to protocol-defined criteria during the first treatment cycle of EMB-01 in combination with chemotherapy regimens
Time frame: Up to Cycle 1 (28 days)
Tolerability of EMB-01 in combination with chemotherapy
Outcome Measure: Treatment interruption due to intolerability and relative dose intensity (RDI)
Time frame: From first dose to 30 days after last dose, up to 2 years
Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2CD)
Determination of the MTD and/or RP2CD of EMB-01 in combination with chemotherapy
Time frame: Through study completion, up to 2 years
Cmax
Time frame: Predose, 0, 0.25, 1.5, 24, 48, 72hours post-dose
Ctrough
Time frame: Predose, 0, 0.25, 1.5, 24, 48, 72hours post-dose
Objective response rate (ORR)
defined as the proportion of participants achieving CR or PR per RECIST v1.1
Time frame: From first dose until the date of first documented progression or date of death from any cause, whichever comes first, up to 2 years.
Disease control rate (DCR)
defined as the proportion of participants achieving CR, PR, or SD per RECIST v1.1
Time frame: From first dose until the date of first documented progression or date of death from any cause, whichever comes first, up to 2 years
Best Overall Response (BOR)
defined as the best response achieved at any time during study treatment, per RECIST v1.1, categorized as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD).
Time frame: From first dose until the date of first documented progression or date of death from any cause, whichever comes first, up to 2 years
Duration of Response (DOR)
defined as the time from the first documentation of objective response (CR or PR per RECIST v1.1) to the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first.
Time frame: From first dose until the date of first documented progression or date of death from any cause, whichever comes first, up to 2 years
Clinical Benefit Rate (CBR)
defined as the proportion of participants achieving CR, PR, or durable SD (≥ 6 months) per RECIST v1.1.
Time frame: From first dose until the date of first documented progression or date of death from any cause, whichever comes first, up to 2 years
Progression-Free Survival (PFS)
defined as the time from the first study treatment dose to the first documentation of progressive disease (PD per RECIST v1.1) or death due to any cause, whichever occurs first.
Time frame: From first dose until the date of first documented progression or date of death from any cause, whichever comes first, up to 2 years
Incidence anti-drug antibodies (ADAs)
Incidence and titer of ADAs against EMB-01 when administered in combination with chemotherapy
Time frame: From C1D1 pre-dose until 30 days after last dose, up to 2 years
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