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

A Phase IB/II Clinical Study on the Safety, Tolerability and Efficacy of HRS-4642 in Combination With Anti-tumor Medication in Subjects With Advanced Solid Tumors

The study is being conducted to evaluate the safety, tolerability, and efficacy of HRS-4642 in combination with antitumor medicine in patients with advanced solid tumors harboring KRAS G12D mutation.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced KRAS G12D Mutant Solid Tumors
• Intervention / Treatment: Drug: HRS-4642; Drug: Adebrelimab; Drug: Pemetrexed Disodium for Injection、Cisplatin Injection、Carboplatin for Injection; Drug: SHR-9839; Drug: Cetuximab Solution for Infusion

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200120
      • Shanghai East Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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 and ≤75 years old.
3. ECOG performance status of 0-1.
4. With a life expectancy of ≥12 weeks.
5. With unresectable locally advanced or metastatic solid tumors harbouring with KRAS G12D mutation confirmed by central laboratory testing.
6. Need to provided tumor tissue samples for genetic testing.
7. Have at least one measurable lesion according to RECIST1.1, and the dose-escalation phase allows no measurable lesion.
8. Adequate laboratory parameters during the screening period.

Exclusion Criteria:

1. Accompanied by untreated or active central nervous system (CNS) metastases. Subjects with a history or current history of meningeal metastasis.
2. Systemic antitumor therapy was received 4 weeks before the start of the study.
3. Palliative radiotherapy was completed within 14 days before the first dose.
4. Toxicity and/or complications from previous interventions did not return to NCI-CTCAE level ≤1 or exclusion criteria.
5. Subjects with known or suspected interstitial pneumonia.
6. Moderate or severe ascites with clinical symptoms; Uncontrolled or moderate or higher pleural effusion or pericardial effusion.
7. Have poorly controlled or severe cardiovascular disease.
8. Subjects with active hepatitis B or active hepatitis C.
9. A history of immunodeficiency, including a positive HIV test, other acquired or congenital immunodeficiency disorders, or a history of organ transplantation.
10. The presence of uncontrolled mental illness and other conditions known to affect the completion of the study process, such as alcohol, drug or substance abuse, and criminal detention.
11. Any other factors that may increase the risk of participating in the study, interfere with the study results, or make participation in the study inappropriate as judged by investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; For HRS-4642 in combination with Adebrelimab or in combination with Adebrelimab and chemotherapy for advanced solid tumors with KRAS G12D mutations.	Drug: HRS-4642; administrated per dose level in which the patients are assigned; Drug: Adebrelimab; administrated per dose level in which the patients are assigned; Drug: Pemetrexed Disodium for Injection、Cisplatin Injection、Carboplatin for Injection; administered as prescribed by the investigator.
Experimental: Arm 2; For HRS-4642 in combination with SHR-9839，for advanced solid tumors with KRAS G12D mutations.	Drug: HRS-4642; administrated per dose level in which the patients are assigned; Drug: SHR-9839; administrated per dose level in which the patients are assigned
Experimental: Arm 3; For HRS-4642 in combination with Cetuximab Solution for Infusion，for advanced solid tumors with KRAS G12D mutations	Drug: HRS-4642; administrated per dose level in which the patients are assigned; Drug: Cetuximab Solution for Infusion; administrated per dose level in which the patients are assigned

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase IB: Safety endpoints: adverse events (AEs).	Assess safety and tolerability by way of adverse events (CTCAE v5.0).	24 months
Phase IB： Maximum tolerated dose (MTD)	Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of treatment.	From Day 1 to Day 21
Phase IB：Recommended phase 2 dose (RP2D)	RP2D will be determined on the basis of evaluation on safety, PK, efficacy data in dose escalation and dose expansion stages.	24 months
Phase II: Overall response rate (ORR).	Evaluated by RECIST v1.1.	24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy endpoints: Overall response rate (ORR).	Evaluated by RECIST v1.1.	24 months
Efficacy endpoints: Duration of response (DoR).	Evaluated by RECIST v1.1.	24 months
Efficacy endpoints: Disease control rate (DCR).	Evaluated by RECIST v1.1.	24 months
Efficacy endpoints: Progression free survival (PFS).	Evaluated by RECIST v1.1.	24 months
Efficacy endpoints: overall survival (OS).	Evaluated by RECIST v1.1.	24 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: April 19, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Drug Administration Routes; Drug Therapy; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Pemetrexed; Injections
• Other Study ID Numbers: HRS-4642-201

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