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

Hengrui Medicine

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Advanced KRAS G12D Mutant Solid Tumors

Treatments: Drug: Cetuximab Solution for Infusion; Drug: Adebrelimab; Drug: HRS-4642; Drug: SHR-9839; Drug: Pemetrexed Disodium for Injection、Cisplatin Injection、Carboplatin for Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT06385678

HRS-4642-201

Details and patient eligibility

About

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.

Enrollment: 47 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

47 participants in 3 patient groups

Arm 1

Experimental group

Description:

For HRS-4642 in combination with Adebrelimab or in combination with Adebrelimab and chemotherapy for advanced solid tumors with KRAS G12D mutations.

Treatment:

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

Drug: HRS-4642

Drug: Adebrelimab

Arm 2

Experimental group

Description:

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

Treatment:

Drug: SHR-9839

Drug: HRS-4642

Arm 3

Experimental group

Description:

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

Treatment:

Drug: HRS-4642

Drug: Cetuximab Solution for Infusion