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
- Are there results?
- Not yet: the study is under way
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
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06385678
- Acronym / sponsor ID
- HRS-4642-201
- Conditions
- Advanced KRAS G12D Mutant Solid Tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Jiangsu HengRui Medicine Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 5 Jul 2024 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 26 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: HRS-4642, Drug: Adebrelimab, Drug: Pemetrexed Disodium for Injection、Cisplatin Injection、Carboplatin for InjectionFor HRS-4642 in combination with Adebrelimab or in combination with Adebrelimab and chemotherapy for advanced solid tumors with KRAS G12D mutations. |
| Arm 2 | Experimental | Drug: HRS-4642, Drug: SHR-9839For HRS-4642 in combination with SHR-9839，for advanced solid tumors with KRAS G12D mutations. |
| Arm 3 | Experimental | Drug: HRS-4642, Drug: Cetuximab Solution for InfusionFor HRS-4642 in combination with Cetuximab Solution for Infusion，for advanced solid tumors with KRAS G12D mutations |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HRS-4642administrated per dose level in which the patients are assigned | Drug | Arm 1, Arm 2, Arm 3 |
| Adebrelimabadministrated per dose level in which the patients are assigned | Drug | Arm 1 |
| SHR-9839administrated per dose level in which the patients are assigned | Drug | Arm 2 |
| Pemetrexed Disodium for Injection、Cisplatin Injection、Carboplatin for Injectionadministered as prescribed by the investigator. | Drug | Arm 1 |
| Cetuximab Solution for Infusionadministrated per dose level in which the patients are assigned | Drug | Arm 3 |
Primary outcome
Phase IB: Safety endpoints: adverse events (AEs).
Time frame: 24 months
Assess safety and tolerability by way of adverse events (CTCAE v5.0).
Phase IB： Maximum tolerated dose (MTD)
Time frame: 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)
Time frame: 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).
Time frame: 24 months.
Evaluated by RECIST v1.1.
5 secondary outcomes
Efficacy endpoints: Overall response rate (ORR).
Time frame: 24 months
Efficacy endpoints: Duration of response (DoR).
Time frame: 24 months
Efficacy endpoints: Disease control rate (DCR).
Time frame: 24 months
Efficacy endpoints: Progression free survival (PFS).
Time frame: 24 months
Efficacy endpoints: overall survival (OS).
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase IB: Safety endpoints: adverse events (AEs). (time frame: 24 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2025.