A Study of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation
Phase 1
- Conditions
- Advanced KRAS G12D Mutant Solid Tumors
- Interventions
- Registration Number
- NCT06385678
- Lead Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 70
Inclusion Criteria
- 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.
Exclusion Criteria
- 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.
- Toxicity and/or complications from previous interventions did not return to NCI-CTCAE level ≤1 or exclusion criteria.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm 1 HRS-4642 For HRS-4642 in combination with Adebrelimab or in combination with Adebrelimab and chemotherapy for advanced solid tumors with KRAS G12D mutations. Arm 1 Adebrelimab For HRS-4642 in combination with Adebrelimab or in combination with Adebrelimab and chemotherapy for advanced solid tumors with KRAS G12D mutations. Arm 1 Pemetrexed Disodium for Injection、Cisplatin Injection、Carboplatin for Injection For HRS-4642 in combination with Adebrelimab or in combination with Adebrelimab and chemotherapy for advanced solid tumors with KRAS G12D mutations. Arm 2 HRS-4642 For HRS-4642 in combination with SHR-9839，for advanced solid tumors with KRAS G12D mutations. Arm 3 HRS-4642 For HRS-4642 in combination with Cetuximab Solution for Infusion，for advanced solid tumors with KRAS G12D mutations Arm 3 Cetuximab Solution for Infusion For HRS-4642 in combination with Cetuximab Solution for Infusion，for advanced solid tumors with KRAS G12D mutations Arm 2 SHR-9839 For HRS-4642 in combination with SHR-9839，for advanced solid tumors with KRAS G12D mutations.
- Primary Outcome Measures
Name Time Method Phase IB: Safety endpoints: adverse events (AEs). 24 months Assess safety and tolerability by way of adverse events (CTCAE v5.0).
Phase IB： Maximum tolerated dose (MTD) From Day 1 to Day 21 Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of treatment.
Phase IB：Recommended phase 2 dose (RP2D) 24 months RP2D will be determined on the basis of evaluation on safety, PK, efficacy data in dose escalation and dose expansion stages.
Phase II: Overall response rate (ORR). 24 months. Evaluated by RECIST v1.1.
- Secondary Outcome Measures
Name Time Method Efficacy endpoints: Overall response rate (ORR). 24 months Evaluated by RECIST v1.1.
Efficacy endpoints: Duration of response (DoR). 24 months Evaluated by RECIST v1.1.
Efficacy endpoints: Disease control rate (DCR). 24 months Evaluated by RECIST v1.1.
Efficacy endpoints: Progression free survival (PFS). 24 months Evaluated by RECIST v1.1.
Efficacy endpoints: overall survival (OS). 24 months Evaluated by RECIST v1.1.
Trial Locations
- Locations (1)
Shanghai East Hospital
🇨🇳Shanghai, Shanghai, China