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

Phase I Study to Evaluate the Safety ,Tolerability, and Pharmacokinetics of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation

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

Study Overview

• Status: Recruiting
• Conditions: Advanced KRAS G12D Mutant Solid Tumors
• Intervention / Treatment: Drug: HRS-4642

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wei Shi; Phone Number: +021-61053363; Email: wei.shi@hengrui.com

Study Locations

• China
  • Shanghai
    • ShangHai, Shanghai, China, 200433
      • Recruiting
      • Shanghai Pulmonary Hospital
      • Principal Investigator: Caicun Zhou

Participation Criteria

Eligibility Criteria

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

Description

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 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: 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.	Drug: HRS-4642; HRS-4642 will be administrated per dose level in which the patients are assigned.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoints: adverse events(AEs), serious adverse events（SAEs）.	Assess safety and tolerability of HRS-4642 by way of adverse events (CTCAE v5.0).	24 months
Dose Limited Toxicity(DLT)	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	from day 1 to Day 21
Maximum tolerated dose (MTD)	Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of HRS-4642 treatment.	From Day 1 to Day 21
RP2D	RP2D will be determined on the basis of evaluation on safety, PK, efficacy data in dose escalation and dose expansion stages.	24 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2022
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: September 5, 2022
• First Submitted That Met QC Criteria: September 5, 2022
• First Posted (Actual): September 9, 2022

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: HRS-4642-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
• product manufactured in and exported from the U.S.: No