A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) of HRS2398 in Subjects With Advanced Malignant Tumors

Shanghai Hengrui Pharmaceutical Co., Ltd.1 site in 1 country28 target enrollmentDecember 20, 2021

ConditionsAdvanced Malignant Tumor

InterventionsHRS2398 Tablets

DrugsHRS2398 Tablets

Overview

Phase: Phase 1
Intervention: HRS2398 Tablets
Conditions: Advanced Malignant Tumor
Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.
Enrollment: 28
Locations: 1
Primary Endpoint: Dose-limiting toxicity（DLT）
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The study is being conducted to determine the dose limited toxicity(DLT) and maximum tolerated dose(MTD) and recommended Phase 2 dose(RP2D) of HRS2398 in subjects with advanced malignant tumor ; The second objectives is to evaluate safety and preliminary efficacy and PK profile of HRS2398 in subjects with advanced malignant tumor ; Exploratory cohort is to explore the relationship between gene mutation and efficacy and resistance mechanisms.

Registry

clinicaltrials.gov

Start Date

December 20, 2021

End Date

February 21, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Hengrui Pharmaceutical Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects are able to give voluntary informed consent, understand the study and are willing to follow and complete all the test procedures.
•subjects ≥18 years and ≤70 years.
•Patients with Histologically or cytologically confirmed advanced Malignant tumors who had failed standard treatment or had not been treated with standard therapy.
•Subjects with life expectancy of ≥ 3 months.
•At least one measurable lesion ( RECIST version 1.1).
•Subjects must have adequate organ function (whole blood or component transfusion or BFGF within 2 weeks before 1st dose of study drug is prohibited):
•Absolute neutrophil count (ANC) ≥1.5 x10\^9/L;
•Platelet count ≥ 100 x 10\^9/L;
•Hemoglobin ≥ 90 g / L;
•Total bilirubin (TBil) ≤1.5 x ULN;

Exclusion Criteria

•Untreated and/or uncontrolled brain metastases.
•Patients with clinical symptoms of cancer ascites, pleural effusion, who need to drainage, or who have undergone ascites drainage within 2 weeks prior to the first administration.
•Failure to recover from adverse events from the most recent anti-tumor treatment to CTCAE ≤ grade
•Inability to swallow tablets or gastrointestinal disease, possible impairment of adequate absorption of study drugs.
•Have severe cardiac disease:NYHA class ≥grade II heart failure; unstable angina pectoris；myocardial infarction within 12 months； clinically significant supraventricular or ventricular arrhythmias require treatment or intervention; Hypertension that cannot be well controlled by antihypertensive medication (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg).
•Known active hepatitis C virus, or known active hepatitis B virus.
•Allergic to the HRS2398 or the similar drug.
•Concurrent anticancer treatment or use of other investigational product within 4 weeks before start of trial treatment; major surgery, radiotherapy, chemotherapy within 4 weeks before 1st dose of trial treatment.
•The patient is currently using a drug known to be a strong inhibitor of CYP3A4 within 2 weeks before 1st dose of study drug ，or strong inducer of CYP3A4 within 4 weeks before 1st dose of study drug .
•The investigator determined that the patient should not participate in the study.

Arms & Interventions

Single Arm

HRS2398 Tablets

Intervention: HRS2398 Tablets

Outcomes

Primary Outcomes

Dose-limiting toxicity（DLT）

Time Frame: up to 21 days

Maximum tolerated dose（MTD）

Time Frame: up to 6 months

Recommended Phase II Dose (RP2D)

Time Frame: up to 21 days

Secondary Outcomes

AUC0-t of HRS2398 of Single administration(ingle administration : 30min before administration of Day1, 5min, 0.25 hour, 0.5 hour, 0.75 hour, 1 hour , 2hours, 4hours, 6hours, 8hours, 10hours, 24hours, 48hours, 72hours after administration of Day1)
Number of subjects with adverse events and the severity of adverse events(from the first drug administration to within 30 days for the last treatment dose)
Cmax of HRS2398 of Single administration(Single administration : 30min before administration of Day1, 5min, 0.25 hour, 0.5 hour, 0.75 hour, 1 hour , 2hours, 4hours, 6hours, 8hours, 10hours, 24hours, 48hours, 72hours after administration of Day1)
Tmax of HRS2398 of Single administration(Single administration : 30min before administration of Day1, 5min, 0.25 hour, 0.5 hour, 0.75 hour, 1 hour , 2hours, 4hours, 6hours, 8hours, 10hours, 24hours, 48hours, 72hours after administration of Day1)
AUC0-12 of HRS2398 of Single administration(Single administration : 30min before administration of Day1, 5min, 0.25 hour, 0.5 hour, 0.75 hour, 1 hour , 2hours, 4hours, 6hours, 8hours, 10hours after administration of Day1)
T1/2 of HRS2398 of Single administration(Single administration : 30min before administration of Day1, 5min, 0.25 hour, 0.5 hour, 0.75 hour, 1 hour , 2hours, 4hours, 6hours, 8hours, 10hours, 24hours, 48hours, 72hours after administration of Day1)
Cmax of HRS2398 of Multiple doses(Multiple administration: Day8, Day15, Day17 of Cycle1, Day1 of Cycle2-4 (each cycle is 21 days))
Tmax of HRS2398 of Multiple administration(Multiple administration: Day8, Day15, Day17 of Cycle1, Day1 of Cycle2-4 (each cycle is 21 days))
AUC0-t of HRS2398 of Multiple administration(Multiple administration: Day8, Day15, Day17 of Cycle1, Day1 of Cycle2-4 (each cycle is 21 days))
AUC0-12 of HRS2398 of Multiple administration(Multiple administration: Day8, Day15, Day17 of Cycle1, Day1 of Cycle2-4 (each cycle is 21 days))
T1/2 of HRS2398 of Multiple administration(Multiple administration: Day8, Day15, Day17 of Cycle1, Day1 of Cycle2-4 (each cycle is 21 days))
Bioavailability of fasting state(up to 4 months)
Objective Response Rate(ORR)(up to 4 months)
Disease Control Rate(DCR)(up to 4 months)
Duration of response (DoR)(up to 4 months)
Progression free survival(PFS)(up to 4 months)