Clinical trial NCT05533463: Phase I Study of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation
Official title: Phase I Study to Evaluate the Safety ,Tolerability, and Pharmacokinetics of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced KRAS G12D Mutant Solid Tumors
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-09-09
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm study of HRS-4642
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

1. Subjects must voluntarily agree to participate in the trial and sign a written informed consent form.
2. Male or female ≥ 18 years old.
3. Histologically confirmed diagnosis of advanced solid tumor harbouring with KRAS G12D mutation
4. ECOG performance status of 0-1.
5. With a life expectancy of ≥3 months.
6. Have at least one measurable lesion.
7. Adequate laboratory parameters during the screening period

Exclusion Criteria:

1. Previously received KRAS G12D inhibitors
2. Priot radiotherapy within 28 days for non-thoracic radiation
3. Prior anti-tumor chemotherapy (\< 6 weeks if chemotherapy including nitrosoureas or mitomycin) within 4 weeks before the study drug administration
4. Any unresolved AEs \> Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or inclusion/exclusion criteria level (The investigators determined that safe and controllable toxicity was excluded, such as alopecia and ≤ grade 2 peripheral neuropathy ).
5. Central nervous system (CNS) metastases
6. Major surgical therapy within 28 days prior to the date of signature of informed consent form, or expected major surgery during the study.
7. Known history of hypersensitivity to any components of HRS-4642.
8. Other factors that may affect the study results or lead to forced termination of the study early as judged by investigators.

Primary outcomes:
measure: Safety endpoints: adverse events(AEs), serious adverse events（SAEs）.
timeFrame: 24 months
measure: Dose Limited Toxicity(DLT)
timeFrame: from day 1 to Day 21
measure: Maximum tolerated dose (MTD)
timeFrame: From Day 1 to Day 21
measure: RP2D
timeFrame: 24 months
Secondary outcomes:
measure: Number of Participants With Abnormal Laboratory Values
timeFrame: 24months.
measure: Number of subjects with clinically significant changes in ECOG, vital signs and physical examination.
timeFrame: 24months.
measure: Number of subjects with changes on ECG.
timeFrame: 24months.
measure: Efficacy endpoints: Overall response rate (ORR).
timeFrame: 24months.
measure: Efficacy endpoints: Duration of response (DoR).
timeFrame: 24 months.
measure: Efficacy endpoints: Disease control rate (DCR).
timeFrame: 24months.
measure: Efficacy endpoints: Progression free survival (DoR).
timeFrame: 24months.
measure: Efficacy endpoints: overall survival (OS).
timeFrame: 24minths
measure: Cmax.
timeFrame: 24 months.
measure: Tmax.
timeFrame: 24 months
measure: AUC.
timeFrame: 24 months.
measure: t1/2.
timeFrame: 24 months.
measure: Vz/F.
timeFrame: 24 months.
measure: CL/F.
timeFrame: 24 months.
Other outcomes:
Locations:
city: ShangHai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
Study officials:
References: