This study is an open-label Phase 1, First in Human trial of DR30303, a recombinant humanized monoclonal antibody that targets Claudin18.2 (CLDN18.2). It is composed of humanized variable domain of heavy chain of antibody (VHH) fused with engineered immunoglobulin gamma-1(IgG1) Fc. It is being testing against advanced and/or metastatic solid tumors.
This study is an open, phase I study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of DR30303 in patients with advanced solid tumors. The study is composed of two parts: part 1 is Dose escalation stage and part 2 is Dose expansion stage.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
DR30303 dose level of escalation IV every 3 weeks (Q3W) Day 1, as well as dose expansion with recommended dose level from dose escalation.
Sir Run Run Shaw Hospital，Zhejiang University School of Medicine
Hanzhou, Zhejiang, China
Part 1：Incidence of dose limiting toxicities (DLTs)
Time frame: up to 21 days following first dose
Part 1：Number, severity and duration of treatment-emergent adverse events (TEAEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
Time frame: up to 28 days following last dose
Part 1：Maximum Tolerated Dose (MTD) and/or Biological effective dose (BED) based on safety, tolerability, PK profile and preliminary efficacy data
Time frame: from date of last dose until the date of will receive DR30303 for 1 year or last documented progression，whichever occurs first
Part 2: Recommended Phase 2 Dose (RP2D) based on safety, tolerability, PK profile, and preliminary efficacy data
Time frame: from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first
Part 2: Number, severity and duration of treatment-emergent adverse events (TEAEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
Time frame: up to 28 days following last dose
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
These measure are defined as the proportion of subjects with complete response (CR) or partial response (PR)
Time frame: from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first
Disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
These measure are defined as the proportion of subjects with CR, PR and stable disease (SD)
Time frame: from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first
Duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
These measure are defined as the duration from the first occurrence of confirmed CR or PR until the date of disease progression or death (from any cause)
Time frame: from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first
Clinical Benefit Rate
Defined as Proportion of subjects with CR, PR and duration of SD ≥ 12 weeks
Time frame: from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first
Duration of disease control (DDC) per RECIST v1.1
For subjects with CR, PR, or SD, duration was calculated from the first assessment as CR, PR, or SD until the date of disease progression or death (from any cause)
Time frame: from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first
Progression free survival (PFS) per RECIST v1.1
These measure are defined as time from start of treatment to tumor progression or death from any cause
Time frame: from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first
6-month and 12-month survival rates
Time frame: from date of first dose start until the date of first documented progression , 6 months，12 months whichever came first
Overall survival (OS) per RECIST v1.1
These measure are defined as time from start of treatment to death from any cause
Time frame: from date of first dose start until the date of first documented progression or death from any cause，or the date of will receive DR30303 for 1 year whichever came first
Pharmacokinetic (PK) of DR30303: Maximum serum concentration (Cmax)
Time frame: up to 28 days following last dose
PK of DR30303: Area Under the concentration-time Curve from time zero to the last quantifiable concentration (AUC0-last)
Time frame: up to 28 days following last dose
PK of DR30303: Area Under the concentration-time Curve from time zero to infinity (AUC0-inf)
Time frame: up to 28 days following last dose
PK of DR30303: Time of the maximum concentration (tmax)
Time frame: up to 28 days following last dose
PK of DR30303: Terminal elimination half-life (t1/2)
Time frame: up to 28 days following last dose
Immunogenicity by measurement of Incidence of anti-drug antibodies (ADA)
Time frame: up to 28 days following last dose