The study is being conducted to evaluate the safety and tolerability of HRS-4642 in patients with advanced solid tumors harboring KRAS G12D mutation.To estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose \[RP2D\]) within investigated subject population groups
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
102
HRS-4642 will be administrated per dose level in which the patients are assigned.
Shanghai Pulmonary Hospital
Shanghai, Shanghai Municipality, China
Safety endpoints: adverse events(AEs), serious adverse events(SAEs).
Assess safety and tolerability of HRS-4642 by way of adverse events (CTCAE v5.0).
Time frame: 24 months
Dose Limited Toxicity(DLT)
A DLT is defined as any event meeting the DLT criteria occurring within 21 days of first dose on Cycle 1 Day 1 (C1D1), excluding toxicities clearly related to disease progression or intercurrent illness
Time frame: from day 1 to Day 21
Maximum tolerated dose (MTD)
Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of HRS-4642 treatment.
Time frame: From Day 1 to Day 21
RP2D
RP2D will be determined on the basis of evaluation on safety, PK, efficacy data in dose escalation and dose expansion stages.
Time frame: 24 months
Number of Participants With Abnormal Laboratory Values
Time frame: 24months.
Number of subjects with clinically significant changes in ECOG, vital signs and physical examination.
Time frame: 24months.
Number of subjects with changes on ECG.
Time frame: 24months.
Efficacy endpoints: Overall response rate (ORR).
Evaluated by RECIST v1.1.
Time frame: 24months.
Efficacy endpoints: Duration of response (DoR).
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Evaluated by RECIST v1.1
Time frame: 24 months.
Efficacy endpoints: Disease control rate (DCR).
Evaluated by RECIST v1.1.
Time frame: 24months.
Efficacy endpoints: Progression free survival (DoR).
Evaluated by RECIST v1.1.
Time frame: 24months.
Efficacy endpoints: overall survival (OS).
Evaluated by RECIST v1.1
Time frame: 24minths
Cmax.
Maximal plasma concentration.
Time frame: 24 months.
Tmax.
Time to Cmax.
Time frame: 24 months
AUC.
Area under the plasma concentration-time curve.
Time frame: 24 months.
t1/2.
Terminal-phase elimination half-life.
Time frame: 24 months.
Vz/F.
Apparent volume of distribution during terminal phase after non-intravenous administration.
Time frame: 24 months.
CL/F.
Apparent total clearance of the drug from plasma after oral administration.
Time frame: 24 months.