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

NCT05144061 | Completed Phase 1

• 1 other identifier: HRS2398-I-101
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Malignant Tumor

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (16)

• 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

Study Arms (1)

Single Arm

EXPERIMENTAL

HRS2398 Tablets

Drug: HRS2398 Tablets

Interventions

HRS2398 Tablets DRUG

Take 5mg to 320mg once or twice a day ; Oral administration , 21 days as a cycle.

Single Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ECOG ≤1.
• 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;
• 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;
• Gr ≤ 1.5x ULN or an estimated glomerular filtration rate (eGFR) \> 50 mL/min;
• INR ≤1.5 x ULN and APTT ≤ 1.5 x ULN;
• LVEF≥50%，QTc Male: \<450ms; Female: \<470ms.

You may not qualify if:

• 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 ≤ grade2.
• 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.

Sponsors & Collaborators

• Shanghai Hengrui Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single therapy of HRS2398

Study Record Dates

• First Submitted: October 12, 2021
• First Posted: December 3, 2021
• Study Start: December 20, 2021
• Primary Completion: February 21, 2024
• Study Completion: February 21, 2024
• Last Updated: December 18, 2024

Record last verified: 2022-11

Locations

CN (1)