This is a first-in-human, open-label, multicenter Phase I/II study of MHB048C in patients with advanced solid tumors. The study was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MHB048C monotherapy.
This first-in-human clinical trial of MHB048C comprises two parts: a dose escalation phase and a dose expansion phase. The dose escalation phase is an open-label, multicenter study including dose escalation and PK expansion cohorts. The primary objectives are to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of MHB048C in patients with advanced solid tumors, and to determine the maximum tolerated dose (MTD). In this phase, additional patients may be enrolled in the PK expansion part at dose levels that have completed DLT (dose-limiting toxicity) evaluation. Based on the safety, PK, and preliminary efficacy data from the completed DLT-evaluated dose levels, the sponsor will initiate the dose expansion phase. This phase is an open-label, multicenter, multi-cohort study designed to further evaluate the safety and efficacy of MHB048C monotherapy in patients with mCRPC or other types of advanced solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
200
IV administration of MHB048C Q2W or Q3W; Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and confirmed disease progression.
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
RECRUITING(Dose-Escalation Stage): Dose-Limiting Toxicity (DLT) and Maximum tolerated dose (MTD) for MHB048C
To determine the MTD for further evaluation of IV administration of MHB048C monotherapy in subjects with advanced solid tumors.
Time frame: Up to day 21 from the first dose for Q3W administration.
(Dose-Expansion Stage): Objective tumor response (ORR) determined by investigators according to RECIST v1.1
To determine the recommended Phase II dose (RP2D) of MHB048C for the treatment of selected patients with advanced solid tumors based on the safety and efficacy results from all enrolled subjects.
Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years
ORR determined by investigators according to RECIST v1.1
Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). ORR is evaluated by the number of participants with best overall response of CR and PR (Confirmed CR/PR assessment require at least 1 repeat).
Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years
Duration of response (DOR) determined by investigators according to RECIST v1.1
DoR was defined as the period from the first occurrence of CR or PR to PD or death from any cause. If no PD or death after CR/PR, the cut-off date of progression-free survival (PFS) would be used \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)\].
Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years
Disease control rate (DCR) determined by investigators according to RECIST v1.1
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Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). DCR was evaluated by the number of participants with best overall response of CR, PR and stable disease (SD) \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks); SD shall be assessed at least 5 weeks after the first dose\].
Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years
Radiographic Progression-free survival (rPFS) determined by investigators according to PCWG3
rPFS was defined as the time from random assignment (dose expansion stage) or first dose (dose escalation stage) to radiographic progression on bone lesion.
Time frame: Baseline up until radiographic progression on bone lesion, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years
Overall survival (OS)
OS was defined as the time from random assignment or first dose to death from any cause.
Time frame: Baseline up until death up to approximately 5 years
Incidence and severity of adverse events (AEs), serious adverse events (SAEs), AEs leading to treatment suspension, discontinuation
AE assessed by investigator exclusively related to subject's underlying disease or medical condition \[graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0\].
Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years.
Pharmacokinetic (PK) parameters of total antibody, ADC, and free toxin at various time points
The PK parameters at different time points include: Area Under the Concentration-Time Curve (AUC)
Time frame: From pre-dose to 22 days after the first dose.
Pharmacokinetic (PK) parameters of total antibody, ADC, and free toxin at various time points
The PK parameters at different time points include: Maximum Plasma Concentration (Cmax)
Time frame: From pre-dose to 22 days after the first dose.
Immunogenicity
Proportion of subjects who develop anti-MHB048C antibodies (ADA).
Time frame: From pre-dose to 30 days post end of treatment.