First-in-human, Phase I/II, Multicenter, Open-Label Study of EMB-01 in Patients with Advanced/Metastatic Solid Tumors
This is a first-in-human (FIH), open-label, Phase I/II study of EMB-01, a bispecific Epidermal growth factor receptor (EGFR) and c-Mesenchymal-Epithelial Transition (cMet) antibody, in patients with advanced solid tumors who have progressed on available standard therapies or for which no standard therapy exists. The study consists of two parts: Phase I (dose escalation) and Phase II (cohort expansion). The study is planning to recruit tentatively 33-66 subjects with advanced/metastatic solid tumors in phase I and approximately 42-120 subjects with EGFR mutant and/or cMET aberrated NSCLC who have progressed on or are intolerant to standard treatment(s) (including platinum-based therapy) will be enrolled at the RP2D(s) in phase II part of the study. In phase II, patients will be assigned to five groups according to their molecular status at baseline. The trial will consist of molecular pre-screening period (Phase II only), clinical screening period (-28 to -1 days), treatment cycles (each cycle is 28 days, maximum up to 2 years), and safety follow-up period (30 days after the last dose).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
186
In part 1, patients will receive intravenous infusions of EMB01 weekly (QW). Dose escalation will continue until the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) is reached or all planned doses are administered. In part 2, participants will receive intravenous infusion of EMB-01 at RP2D The duration of each treatment cycle in both part 1 and part 2 is 28 days (4 weeks). Participants may continue to receive study drug until discontinuation criteria are met.
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGBarbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
RECRUITINGGabrail Cancer Center Research
Canton, Ohio, United States
Maximum tolerated dose (MTD) (phase 1 only)
Maximum tolerated dose
Time frame: cycle 1 (1cycle = 28 days)
Adverse Events (AEs), and Serious Adverse Events (SAEs)
Adverse Events, and Serious Adverse Events
Time frame: Screening up to follow-up (30 days after the last dose)
Overall Response Rate (ORR) (phase 2 only)
Overall Response Rate
Time frame: From the date fo dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Maximum Serum Concentration (Cmax)
Maximum Serum Concentration
Time frame: Through treatment discontinuation: an average of 6 months
Area Under the Plasma Concentration-Time Curve (AUC)
Area Under the Plasma Concentration-Time Curve
Time frame: Through treatment discontinuation: an average of 6 months
Trough Serum Concentration (Ctrough)
Trough Serum Concentration
Time frame: Through treatment discontinuation: an average of 6 months
Elimination half-life (t1/2)
Elimination half-life
Time frame: Through treatment discontinuation: an average of 6 months
Clearance (CL)
Clearance
Time frame: Through treatment discontinuation: an average of 6 months
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Guangdong General Hospital
Guangzhou, Guangdong, China
RECRUITINGShanghai Chest Hosptial
Shanghai, Shanghai Municipality, China
RECRUITINGVolume of distribution at steady state (Vss)
volume of distribution at steady state
Time frame: Through treatment discontinuation: an average of 6 months
Accumulation Ratio (AR)
Accumulation Ratio
Time frame: hrough treatment discontinuation: an average of 6 months
Dose Proportionality
Dose Proportionality
Time frame: Through treatment discontinuation: an average of 6 months
Anti-Drug Antibodies (ADA)
Anti-Drug Antibodies
Time frame: Through study completion, an average of 7 months
Duration Of Response (DOR)
Duration Of Response
Time frame: From the date fo dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Progression-Free Survival (PFS)
Progression-free survival
Time frame: Through treatment discontinuation: an average of 6 months