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

September 5, 2025 updated by: Jiangsu HengRui Medicine Co., Ltd.

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

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
102

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200433
        • Shanghai Pulmonary Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety endpoints: adverse events(AEs), serious adverse events（SAEs）.
Time Frame: 24 months
Assess safety and tolerability of HRS-4642 by way of adverse events (CTCAE v5.0).
24 months
Dose Limited Toxicity(DLT)
Time Frame: 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
from day 1 to Day 21
Maximum tolerated dose (MTD)
Time Frame: From Day 1 to Day 21
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
Time Frame: 24 months
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Abnormal Laboratory Values
Time Frame: 24months.
24months.
Number of subjects with clinically significant changes in ECOG, vital signs and physical examination.
Time Frame: 24months.
24months.
Number of subjects with changes on ECG.
Time Frame: 24months.
24months.
Efficacy endpoints: Overall response rate (ORR).
Time Frame: 24months.
Evaluated by RECIST v1.1.
24months.
Efficacy endpoints: Duration of response (DoR).
Time Frame: 24 months.
Evaluated by RECIST v1.1
24 months.
Efficacy endpoints: Disease control rate (DCR).
Time Frame: 24months.
Evaluated by RECIST v1.1.
24months.
Efficacy endpoints: Progression free survival (DoR).
Time Frame: 24months.
Evaluated by RECIST v1.1.
24months.
Efficacy endpoints: overall survival (OS).
Time Frame: 24minths
Evaluated by RECIST v1.1
24minths
Cmax.
Time Frame: 24 months.
Maximal plasma concentration.
24 months.
Tmax.
Time Frame: 24 months
Time to Cmax.
24 months
AUC.
Time Frame: 24 months.
Area under the plasma concentration-time curve.
24 months.
t1/2.
Time Frame: 24 months.
Terminal-phase elimination half-life.
24 months.
Vz/F.
Time Frame: 24 months.
Apparent volume of distribution during terminal phase after non-intravenous administration.
24 months.
CL/F.
Time Frame: 24 months.
Apparent total clearance of the drug from plasma after oral administration.
24 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Jiangsu HengRui Medicine Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 21, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 25, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 5, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 5, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 9, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 8, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 5, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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