A Phase I Clinical Study of HRS-7058 in Patients With Advanced Malignant Tumour

Official title

An Open, Multicenter Phase I Study of Safety, Tolerability, Pharmacokinetics, and Efficacy of HRS-7058 Monotherapy in Patients With Advanced Solid Tumour With KRAS G12C Mutation

Overview

This study is a multicentre, open phase I clinical study of dose escalation, dose extension and efficacy extension of HRS-7058 in subjects with advanced malignant tumour. To evaluate the safety, tolerability, pharmacokinetics and efficacy of HRS-7058.

Interventions

• Drug HRS-7058 capsule/ HRS-7058 tablet
  HRS-7058 capsule/ HRS-7058 tablet

Primary outcome measures

• Dose-limiting toxicity (DLT) [Time frame: From the beginning of first patient in (FPI) to the end of dose escalation phase up to approximately 10 months]
• maximum tolerated dose (MTD) [Time frame: From the beginning of first patient in (FPI) to the end of dose escalation phase up to approximately 10 months]
• Phase II recommended dose (RP2D) [Time frame: From the beginning of first patient in (FPI) to the end of dose escalation phase up to approximately 10 months]
• Safety endpoints: adverse events (AE) [Time frame: From the beginning of first patient in (FPI) to the end of study up to approximately 21 months]]

Secondary outcome measures (5)

• Efficacy endpoints: Objective response rate (ORR) assessed based on RECIST v1.1 criterion [Time frame: From the beginning of first patient in (FPI) to the end of study up to approximately 21 months]
• Efficacy endpoints: duration of response (DoR) assessed based on RECIST v1.1 criterion [Time frame: From the beginning of first patient in (FPI) to the end of study up to approximately 21 months]
• Efficacy endpoints: disease control rate (DCR) assessed based on RECIST v1.1 criterion [Time frame: From the beginn ing of first patient in (FPI) to the end of study up to approximately 21 months]
• Efficacy endpoints: progression-free survival (PFS) assessed based on RECIST v1.1 criterion [Time frame: From the beginn ing of first patient in (FPI) to the end of study up to approximately 21 months]
• Efficacy endpoints: overall survival (OS) [Time frame: From the beginn ing of first patient in (FPI) to the end of study up to approximately 21 months]

Eligibility criteria

Inclusion criteria

• The subjects gave informed consent to the study before participating in, and voluntarily signed informed consent;
• 18 to 75 years old (including both ends), gender is not limited;
• Subjects with locally advanced or metastatic solid tumour confirmed by histopathology;
• Having at least one evaluable or measurable lesion according to the solid tumour response Evaluation Criteria (RECIST 1.1);
• ECOG Performance Status of 0 or 1;
• The expected survival time is more than 3 months;
• Be able to ingest drugs and be able to comply with trial and follow-up procedures;
• Adequate bone marrow and organ function;
• Fertile women must agree to abstain from sex (abstaining from heterosexual intercourse) or use a highly effective method of contraception for at least one week from the time they sign an informed consent form until the last dose of the study drug. The blood HCG test must be negative within 7 days before the start of the study treatment, and must be non-lactating;
• For male patients whose partner is a woman of reproductive age, they must agree to abstain from sex for at least one week from signing the informed consent until the last dose of the study drug, or to use a highly effective method of contraception.

Exclusion criteria

• Accompanied by untreated or active central nervous system (CNS) tumour metastasis;
• Had other malignancies within five years prior to first use of the investigational drug;
• With severe cardiovascular and cerebrovascular disease；
• Refractory nausea, vomiting, or other gastrointestinal disorders that affect the use of oral medications;
• The presence of uncontrolled pleural, abdominal or pericardial effusion;
• Severe infection within 4 weeks prior to initiation of study treatment;
• History of immune deficiency;
• The adverse reactions of previous anti-tumour therapy have not recovered to CTCAE ≤ grade 1;
• Antitumor therapy such as chemotherapy, biotherapy, targeted therapy, immunotherapy, or other unmarketed investigational drug therapy within 4 weeks prior to initial use of the investigational drug;
• Had undergone major organ surgery within 4 weeks prior to the first use of the study drug;
• Women who are pregnant, breastfeeding, or who plan to become pregnant within one week of their last use of the study drug during the study period;
• Known allergies and contraindications to the investigational drug or any of its components;
• In the investigator's judgment, the subjects had other factors that could have affected the study results or led to the forced termination of the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Tianjin Medical University Cancer Institute and Hospital — Tianjin

Identifiers

NCT: NCT06383871 · HRS-7058-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗