A First-in-human Study of HRS2398 Tablets in Subjects With Advanced Malignant Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Malignant Tumor
• Intervention / Treatment: Drug: HRS2398 Tablets

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects are able to give voluntary informed consent, understand the study and are willing to follow and complete all the test procedures.
2. subjects ≥18 years and ≤70 years.
3. Patients with Histologically or cytologically confirmed advanced Malignant tumors who had failed standard treatment or had not been treated with standard therapy.
4. ECOG ≤1.
5. Subjects with life expectancy of ≥ 3 months.
6. At least one measurable lesion ( RECIST version 1.1).

7. Subjects must have adequate organ function (whole blood or component transfusion or BFGF within 2 weeks before 1st dose of study drug is prohibited):

   1. Absolute neutrophil count (ANC) ≥1.5 x10^9/L;
   2. Platelet count ≥ 100 x 10^9/L;
   3. Hemoglobin ≥ 90 g / L;
   4. Total bilirubin (TBil) ≤1.5 x ULN;
   5. Liver function tests alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN, for patients with known liver cancer or liver metastases, AST and ALT ≤ 5 x ULN;
   6. Gr ≤ 1.5x ULN or an estimated glomerular filtration rate (eGFR) > 50 mL/min;
   7. INR ≤1.5 x ULN and APTT ≤ 1.5 x ULN;
   8. LVEF≥50%，QTc Male: <450ms; Female: <470ms.
8. Subjects (males and females) of childbearing potential should be willing to use reliable contraception methods that are deemed effective by the investigator from visit 1 through 180 days following the last dose of study drug.
9. Archived wax lump tumor tissue samples or biopsy and blood sample collection during screening period.
10. As judged by the investigator, can follow protocol.

Exclusion Criteria:

1. Untreated and/or uncontrolled brain metastases.
2. 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.
3. Failure to recover from adverse events from the most recent anti-tumor treatment to CTCAE ≤ grade2.
4. Inability to swallow tablets or gastrointestinal disease, possible impairment of adequate absorption of study drugs.
5. 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).
6. Known active hepatitis C virus, or known active hepatitis B virus.
7. Allergic to the HRS2398 or the similar drug.
8. 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.
9. 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 .
10. The investigator determined that the patient should not participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; HRS2398 Tablets	Drug: HRS2398 Tablets; Take 5mg to 320mg once or twice a day ; Oral administration , 21 days as a cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose-limiting toxicity（DLT）	up to 21 days
Maximum tolerated dose（MTD）	up to 6 months
Recommended Phase II Dose (RP2D)	up to 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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-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
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	PK blood samples from subjects were collected for bioavailability ，Postprandial AUC divided by fasting AUC	up to 4 months
Objective Response Rate(ORR)	Radiological scans performed at baseline then every 6 weeks until objective radiological disease progression	up to 4 months
Disease Control Rate(DCR)	Complete response + Partial response + Stable disease (CR+PR+SD) based on RECIST 1.1	up to 4 months
Duration of response (DoR)	Time from documentation of tumor response to disease progression assessed among patients who had an objective response	up to 4 months
Progression free survival(PFS)	Defined as Progression free survival per RECIST 1.1 criteria according to Investigator's assessment	up to 4 months

Collaborators and Investigators

• Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2021
• Primary Completion (Actual): February 21, 2024
• Study Completion (Actual): February 21, 2024

Study Registration Dates

• First Submitted: October 12, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): December 3, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2024
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: HRS2398-I-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No