Phase I Study of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation

Phase 1

Recruiting

• Conditions: Advanced KRAS G12D Mutant Solid Tumors
• Interventions: Drug: HRS-4642

• Registration Number: NCT05533463
• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-05
• Study First Submitted QC: 2022-09-05
• Study First Posted: 2022-09-09
• Study Start: 2022-09-15
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-03
• Last Update Posted: 2023-11-07
• Primary Completion: 2024-04-30
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 108

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HRS-4642	HRS-4642	In Dose Escalation: HRS-4642 will be injected QW. Six dose levels are preset. In Dose Expansion: 1 to 2 dose cohorts will be selected for dose expansion stage. In Indication Expansion: Enrollment into the dose expansion cohorts may be from any eligible solid tumor type.

Primary Outcome Measures

Name	Time	Method
Dose Limited Toxicity(DLT)	from day 1 to Day 21	A DLT is defined as any event meeting the DLT criteria occurring within 21 days of first dose on Cycle 1 Day 1 (C1D1), excluding toxicities clearly related to disease progression or intercurrent illness
Maximum tolerated dose (MTD)	From Day 1 to Day 21	Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of HRS-4642 treatment.
Safety endpoints: adverse events(AEs), serious adverse events（SAEs）.	24 months	Assess safety and tolerability of HRS-4642 by way of adverse events (CTCAE v5.0).
RP2D	24 months	RP2D will be determined on the basis of evaluation on safety, PK, efficacy data in dose escalation and dose expansion stages.

Secondary Outcome Measures

Name	Time	Method
AUC.	24 months.	Area under the plasma concentration-time curve.
t1/2.	24 months.	Terminal-phase elimination half-life.
Number of subjects with changes on ECG.	24months.
Number of subjects with clinically significant changes in ECOG, vital signs and physical examination.	24months.
Efficacy endpoints: Progression free survival (DoR).	24months.	Evaluated by RECIST v1.1.
Vz/F.	24 months.	Apparent volume of distribution during terminal phase after non-intravenous administration.
Efficacy endpoints: Disease control rate (DCR).	24months.	Evaluated by RECIST v1.1.
Efficacy endpoints: overall survival (OS).	24minths	Evaluated by RECIST v1.1
Cmax.	24 months.	Maximal plasma concentration.
Number of Participants With Abnormal Laboratory Values	24months.
Efficacy endpoints: Overall response rate (ORR).	24months.	Evaluated by RECIST v1.1.
Efficacy endpoints: Duration of response (DoR).	24 months.	Evaluated by RECIST v1.1
Tmax.	24 months	Time to Cmax.
CL/F.	24 months.	Apparent total clearance of the drug from plasma after oral administration.

Trial Locations

Locations (1)

Shanghai Pulmonary Hospital; 🇨🇳 ShangHai, Shanghai, China