Advanced KRAS G12D Mutant Solid TumorsPhase 1/2NCT06385678
A Study of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation
A Phase 1/2 study testing HRS-4642, Adebrelimab and SHR-9839 in people with Advanced KRAS G12D Mutant Solid Tumors, run by Jiangsu HengRui Medicine Co., Ltd. at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced KRAS G12D Mutant Solid Tumors
- What is being tested?
- HRS-4642, Adebrelimab and SHR-9839
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteChina
- Study dates
- 5 Jul 2024to Aug 2026
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Advanced KRAS G12D Mutant Solid Tumors
- Being tested
- HRS-4642, Adebrelimab, SHR-9839, Pemetrexed Disodium for Injection、Cisplatin Injection、Carboplatin for Injection, Cetuximab Solution for Infusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HRS-4642Drug
administrated per dose level in which the patients are assigned
AdebrelimabDrug
administrated per dose level in which the patients are assigned
SHR-9839Drug
administrated per dose level in which the patients are assigned
Pemetrexed Disodium for Injection、Cisplatin Injection、Carboplatin for InjectionDrug
administered as prescribed by the investigator.
Cetuximab Solution for InfusionDrug
administrated per dose level in which the patients are assigned
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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 Receives: Drug: HRS-4642; Drug: Cetuximab Solution for Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase IB: Safety endpoints: adverse events (AEs).
Assess safety and tolerability by way of adverse events (CTCAE v5.0).
Measured: 24 months
Phase IB： Maximum tolerated dose (MTD)
Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of treatment.
Measured: 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.
Measured: 24 months
Phase II: Overall response rate (ORR).
Evaluated by RECIST v1.1.
Measured: 24 months.
Secondary outcomes (5)
Efficacy endpoints: Overall response rate (ORR).
Evaluated by RECIST v1.1.
Measured: 24 months
Efficacy endpoints: Duration of response (DoR).
Evaluated by RECIST v1.1.
Measured: 24 months
Efficacy endpoints: Disease control rate (DCR).
Evaluated by RECIST v1.1.
Measured: 24 months
Efficacy endpoints: Progression free survival (PFS).
Evaluated by RECIST v1.1.
Measured: 24 months
Efficacy endpoints: overall survival (OS).
Evaluated by RECIST v1.1.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2024
- Study start5 Jul 2024
- Primary completionDec 2025 (estimated)
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced KRAS G12D Mutant Solid TumorsStudies of the same condition, open and under way.
- More trials run by Jiangsu HengRui Medicine Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06385678
- Sponsor's protocol ID
- HRS-4642-201
- Status last verified
- Aug 2025
- First submitted
- 19 Apr 2024
- Last updated
- 19 Sep 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided