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

NCT06385678 | Active Not Recruiting Phase 1

• 1 other identifier: HRS-4642-201
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced KRAS G12D Mutant Solid Tumors

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (5)

• Efficacy endpoints: Overall response rate (ORR).

  24 months

• Efficacy endpoints: Duration of response (DoR).

  24 months

• Efficacy endpoints: Disease control rate (DCR).

  24 months

• Efficacy endpoints: Progression free survival (PFS).

  24 months

• Efficacy endpoints: overall survival (OS).

  24 months

Study Arms (3)

Arm 1

EXPERIMENTAL

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; Drug: Adebrelimab; Drug: Pemetrexed Disodium for Injection、Cisplatin Injection、Carboplatin for Injection

Arm 2

EXPERIMENTAL

For HRS-4642 in combination with SHR-9839，for advanced solid tumors with KRAS G12D mutations.

Drug: HRS-4642; Drug: SHR-9839

Arm 3

EXPERIMENTAL

For HRS-4642 in combination with Cetuximab Solution for Infusion，for advanced solid tumors with KRAS G12D mutations

Drug: HRS-4642; Drug: Cetuximab Solution for Infusion

Interventions

HRS-4642 DRUG

administrated per dose level in which the patients are assigned

Arm 1; Arm 2; Arm 3

Adebrelimab DRUG

administrated per dose level in which the patients are assigned

Arm 1

SHR-9839 DRUG

administrated per dose level in which the patients are assigned

Arm 2

Pemetrexed Disodium for Injection、Cisplatin Injection、Carboplatin for Injection DRUG

administered as prescribed by the investigator.

Arm 1

Cetuximab Solution for Infusion DRUG

administrated per dose level in which the patients are assigned

Arm 3

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must voluntarily agree to participate in the trial and sign a written informed consent form.
• Male or female ≥ 18 years old and ≤75 years old.
• ECOG performance status of 0-1.
• With a life expectancy of ≥12 weeks.
• With unresectable locally advanced or metastatic solid tumors harbouring with KRAS G12D mutation confirmed by central laboratory testing.
• Need to provided tumor tissue samples for genetic testing.
• Have at least one measurable lesion according to RECIST1.1, and the dose-escalation phase allows no measurable lesion.
• Adequate laboratory parameters during the screening period.

You may not qualify if:

• Accompanied by untreated or active central nervous system (CNS) metastases. Subjects with a history or current history of meningeal metastasis.
• Systemic antitumor therapy was received 4 weeks before the start of the study.
• Palliative radiotherapy was completed within 14 days before the first dose.
• Subjects with known or suspected interstitial pneumonia.
• Moderate or severe ascites with clinical symptoms; Uncontrolled or moderate or higher pleural effusion or pericardial effusion.
• Have poorly controlled or severe cardiovascular disease.
• Subjects with active hepatitis B or active hepatitis C.
• A history of immunodeficiency, including a positive HIV test, other acquired or congenital immunodeficiency disorders, or a history of organ transplantation.
• 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.
• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

Location

MeSH Terms

Interventions

Pemetrexed; Injections

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Drug Administration Routes; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2024
• First Posted: April 26, 2024
• Study Start: July 5, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): August 1, 2026
• Last Updated: September 19, 2025

Record last verified: 2025-08

Locations

CN (1)