QLC5508 is a fully humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on solid tumor cells. The objectives of this study are to investigate the safety, tolerability, pharmacokinetics and anti-tumor activity of QLC5508 in combination with other anti-cancer agents in patients with advanced solid tumor patients.
This is a phase Ib/II, open-label, multi-center, dose-escalation and expansion in Chinese subjects with advanced solid tumors. This study is in design allowing assessment of safety, tolerability, pharmacokinetics and anti-tumor activity of QLC5508 in combination with other anti-cancer agents. The target population of dose escalation part is patients have progressed on or intolerant to available standard therapies, and the dose expansion part will enroll patients who have not received prior treatment for advanced/metastatic disease.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
444
Shanghai East Hospital
Shanghai, China
RECRUITINGMaximum tolerated dose (MTD) for combination-treatments (Phase Ib)
To determine the MTD for further evaluation of QLC5508 with other anti-cancer agents in participants with advanced solid tumors
Time frame: Up to day 21 (Q3W combination) or day 28 (Q2W combination) from the first dose
Recommended Phase II Dose (RP2D) for combination-treatments (Phase Ib)
To determine the RP2D for further evaluation of QLC5508 with other anti-tumor agents in participants with advanced solid tumors
Time frame: Up to day 21 (Q3W combination) or day 28 (Q2W combination) from the first dose
Objective response rate (ORR) determined by investigators (Phase II)
ORR is defined as proportion of participants with best overall response of complete response (CR) and partial response (PR) \[Confirmed CR/PR assessment require at least one repeat (4-6 weeks)\] evaluated by investigator according to RECIST v1.1
Time frame: Approximately 12 months
ORR determined by investigators (Phase Ib)
ORR is defined as proportion of participants with best overall response of CR and PR \[Confirmed CR/PR assessment require at least one repeat (4-6 weeks)\] evaluated by investigator according to RECIST v1.1
Time frame: Approximately 12 months
Disease control rate (DCR) determined by investigators (Phase Ib and II)
DCR is defined as proportion of participants with best overall response of CR, PR and stable disease (SD) evaluated by investigator according to RECIST v1.1 \[Confirmed CR/PR assessment require at least one repeat (4-6 weeks)\]
Time frame: Approximately 12 months
Duration of response (DOR) determined by investigators (Phase Ib and II)
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200 mg, Q3W,administered as an IV infusion
175 mg/m2, Q3W,administered as an IV infusion
800 mg/m2,Q3W(arm:QLC5508, QL2107 and 5-FU),administered as an IV infusion;1200 mg/m2, Q2W(arm:QLC5508, Oxaliplatin, 5-FU,and leucovorin),administered as an IV infusion
30 mg/m2, Q2W,administered as an IV infusion
DOR is defined as the period from the first occurrence of CR or PR to PD or death from any cause \[Confirmed CR/PR assessment require at least one repeat (4-6 weeks)\]
Time frame: Approximately 12 months
Progression-free survival (PFS) determined by investigators (Phase Ib and II)
PFS is defined as the time from the first dose to PD or death from any cause.
Time frame: Approximately 12 months
Overall survival (OS) (Phase Ib and II)
OS is defined as the time from the first dose to death from any cause
Time frame: Approximately 24 months
Incidence and severity of adverse events (AEs) (Phase II)
Any untoward medical occurrence in a clinical study participant, which may manifest as symptoms, signs, diseases, or laboratory abnormalities, are assessed by investigator according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), v5.0
Time frame: From the first dose through 90 days post end of treatment
Observed maximum plasma concentration (Cmax) of QLC5508 in advanced solid tumor (Phase Ib and II)
Cmax will be obtained after administration of the first dose of QLC5508
Time frame: From pre-dose to study completion, approximately 24 months
Time to reach maximum plasma concentration (Tmax) of QLC5508 (Phase Ib)
Tmax will be obtained after administration of the first dose of QLC5508
Time frame: From pre-dose to study completion, approximately 24 months
Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of QLC5508 (Phase Ib)
Area under the plasma concentration versus time curve from time zero to the last sampling time when the concentration was no less than the lower limit of quantification (LLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
Time frame: From pre-dose to study completion, approximately 24 months]
Observed maximum plasma concentration (Cmax) of QL1706 in advanced solid tumor (Phase Ib and II)
Cmax will be obtained after administration of the first dose of QL1706
Time frame: From pre-dose to study completion, approximately 24 months
Observed maximum plasma concentration (Cmax) of QL2107 in advanced solid tumor (Phase Ib and II)
Cmax will be obtained after administration of the first dose of QL2107
Time frame: From pre-dose to study completion, approximately 24 months
Percentage of participants with antibodies to QLC5508 in serum (Phase Ib and II)
Serum samples were collected for the determination of anti-drug antibody (ADA) at designated time points.
Time frame: From pre-dose to study completion, approximately 24 months
Percentage of participants with antibodies to QL1706 in serum (Phase Ib and II)
Serum samples were collected for the determination of ADA at designated time points
Time frame: From pre-dose to study completion, approximately 24 months