This is a multi-center, open-label, dose escalation and dose expansion, Phase 1 study to evaluate the safety, tolerability, PK and preliminary anti-tumor activity of CMG901. The dose escalation phase (Part A) will determine the MTD of CMG901 in subjects with relapsed and/or refractory advanced solid tumor for which there is no available standard therapy likely to confer clinical benefit, or the subject is not a candidate for such available therapy based on a modified 3+3 dose escalation design (an accelerated dose titration design followed by traditional 3+3 dose escalation design). The dose expansion phase (Part B) will be conducted in subjects with advanced solid cancer with failure of standard treatment or no standard treatment who are Claudin 18.2 positive to preliminarily explore the efficacy and to determine the RP2D of CMG901.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
176
CMG901 will be administered intravenously (IV) on Day 1 of every 21-day cycle. Individual subjects may continue study treatment until confirmed Progressive Disease(PD), unacceptable toxicity, initiation of new anti-tumor therapy, withdrawal from the study, or death, whichever occurs first.
Sun Yat-sen University Cancer Center (SYSUCC)
Guangzhou, Guangdong, China
Henan Cancer Hospital
Zhengzhou, Henan, China
West China Hospital of Sichuan University
Chengdu, Sichuan, China
Affiliated Hospital of Hebei University
Baoding, China
Hunan Cancer Hospital
Changsha, China
Sichuan Cancer Hospital
Part A: Incidence of adverse events.Abnormal laboratory parameters, vital signs, 12-lead electrocardiogram and physical examination. Occurrence of Dose-limiting toxicity
Time frame: Up to 30 days post the last dose, initiation of new anti-tumor therapy, withdrawal from the study, or death, whichever occurs first. DLTs are up to 21 days after the first dose
Part A: To determine the maximum tolerated dose (MTD) of CMG901
Time frame: Up to 21 days after the first dose
Part B: To preliminarily evaluate the Objective Response Rate (ORR) per RECIST v1.1 of CMG901 in subjects with Claudin 18.2-positive advanced solid cancer
Time frame: Up to 24 months
Part B: Recommended phase II dose
Time frame: Up to 24 months
Part A & Part B: Area Under the Curve from 0 to the time of the last measurable concentration [AUC(0-last)]
Time frame: 21 days after the first dose
Part A & Part B: Area Under the Curve over a dosing interval [AUC(0-tau)]
Time frame: 21 days after the first dose
Part A & Part B: Area Under the Curve from 0 to infinity [AUC(0-inf)]
Time frame: 21 days after the first dose
Part A & Part B: Peak Plasma Concentration (Cmax)
Time frame: 21 days after the first dose
Part A & Part B: Time of Maximum Observed Concentration (Tmax)
Time frame: 21 days after the first dose
Part A & Part B: Terminal elimination half-life (t1/2)
Time frame: 21 days after the first dose
Part A & Part B: Clearance (CL)
Time frame: 21 days after the first dose
Part A & Part B: Volume of distribution (Vz)
Time frame: 21 days after the first dose
Part A & Part B: Observed concentration at the end of a dosing interval(Ctrough)
Time frame: 21 days after the first dose
Part A & Part B: Area Under the Curve from 0 to the time of the last measurable concentration [AUC(0-last)]
Time frame: up to 24 months
Part A & Part B: Area Under the Curve over a dosing interval [AUC(0-tau)]
Time frame: up to 24 months
Part A & Part B: Peak Plasma Concentration (Cmax)
Time frame: up to 24 months
Time of maximum observed concentration (Tmax)
Time frame: up to 24 months
Part A & Part B: Terminal elimination half-life (t1/2)
Time frame: up to 24 months
Part A & Part B: Clearance (CL)
Time frame: up to 24 months
Part A & Part B: Volume of distribution (Vz)
Time frame: up to 24 months
Part A & Part B: Volume of distribution at steady-state (Vss)
Time frame: up to 24 months
Part A & Part B: Minimum concentration (Cmin)
Time frame: up to 24 months
Part A & Part B: Observed concentration at the end of a dosing interval (Ctrough)
Time frame: up to 24 months
Part A & Part B: Accumulation ratios of peak plasma concentration (Cmax) for multiple doses
Time frame: up to 24 months
Part A & Part B: Accumulation ratios of area under the curve over a dosing interval [AUC(0-tau)] for multiple doses
Time frame: up to 24 months
Part A & Part B: Incidence of anti-CMG901
Time frame: up to 24 months
Part A & Part B: Disease Control Rate (DCR) per RECIST v1.1
Time frame: up to 24 months
Part A & Part B: Duration of Response (DoR) per RECIST v1.1
Time frame: up to 24 months
Part A & Part B: Progression Free Survival (PFS) per RECIST v1.1
Time frame: up to 24 months
Part A&B:To evaluate the correlation between clinical efficacy of CMG901 and Claudin 18.2 expression
Time frame: up to 24 months
Part A: Objective Response Rate (ORR) per RECIST v1.1
Time frame: up to 24 months
Part A & Part B: Overall Survival (OS)
Time frame: up to 24 months
Part B: Incidence of adverse events graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Abnormal laboratory parameters, vital signs, 12-lead electrocardiogram and physical examination
Time frame: Up to 30 days post the last dose, initiation of new anti-tumor therapy, withdrawal from the study, or death, whichever occurs first
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Chengdu, China
Chongqing University Cancer Hospital
Chongqing, China
Fujian Cancer Hosppital
Fuzhou, China
Fujian Medical University Union Hospital
Fuzhou, China
The First Affiliated Hospital of Fujian Medical University
Fuzhou, China
...and 22 more locations