Advanced KRAS G12D Mutant Solid TumorsPhase 1NCT05533463
Phase I Study of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation
A Phase 1 study testing HRS-4642 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 and tolerability of HRS-4642 in patients with advanced solid tumors harboring KRAS G12D mutation.To estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose [RP2D]) within investigated subject population groups Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced KRAS G12D Mutant Solid Tumors
- What is being tested?
- HRS-4642
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 1 siteChina
- Study dates
- 21 Sep 2022to 30 Dec 2025
- Phase
- Phase 1
- 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 years and older
- 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.
- Histologically confirmed diagnosis of advanced solid tumor harbouring with KRAS G12D mutation
- ECOG performance status of 0-1.
- With a life expectancy of ≥3 months.
- Have at least one measurable lesion.
- Adequate laboratory parameters during the screening period
Who cannot join
- Previously received KRAS G12D inhibitors
- Priot radiotherapy within 28 days for non-thoracic radiation
- Prior anti-tumor chemotherapy (< 6 weeks if chemotherapy including nitrosoureas or mitomycin) within 4 weeks before the study drug administration
- Any unresolved AEs > Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or inclusion/exclusion criteria level (The investigators determined that safe and controllable toxicity was excluded, such as alopecia and ≤ grade 2 peripheral neuropathy ).
- Central nervous system (CNS) metastases
- Major surgical therapy within 28 days prior to the date of signature of informed consent form, or expected major surgery during the study.
- Known history of hypersensitivity to any components of HRS-4642.
- Other factors that may affect the study results or lead to forced termination of the study early as judged by investigators.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Study to Evaluate the Safety ,Tolerability, and Pharmacokinetics of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation
The study is being conducted to evaluate the safety and tolerability of HRS-4642 in patients with advanced solid tumors harboring KRAS G12D mutation.To estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose [RP2D]) within investigated subject population groups
- Conditions
- Advanced KRAS G12D Mutant Solid Tumors
- Being tested
- HRS-4642
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HRS-4642Drug
HRS-4642 will be administrated per dose level in which the patients are assigned.
| Study group | Role | What they receive |
|---|---|---|
| HRS-4642 | Experimental | In Dose Escalation:
HRS-4642 will be injected QW. Six dose levels are preset.
In Dose Expansion:
1 to 2 dose cohorts will be selected for dose expansion stage.
In Indication Expansion:
Enrollment into the dose expansion cohorts may be from any eligible solid tumor type. Receives: Drug: HRS-4642 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety endpoints: adverse events(AEs), serious adverse events（SAEs）.
Assess safety and tolerability of HRS-4642 by way of adverse events (CTCAE v5.0).
Measured: 24 months
Dose Limited Toxicity(DLT)
A DLT is defined as any event meeting the DLT criteria occurring within 21 days of first dose on Cycle 1 Day 1 (C1D1), excluding toxicities clearly related to disease progression or intercurrent illness
Measured: from day 1 to Day 21
Maximum tolerated dose (MTD)
Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of HRS-4642 treatment.
Measured: From Day 1 to Day 21
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
Secondary outcomes (14)
Number of Participants With Abnormal Laboratory Values
Measured: 24months.
Number of subjects with clinically significant changes in ECOG, vital signs and physical examination.
Measured: 24months.
Number of subjects with changes on ECG.
Measured: 24months.
Efficacy endpoints: Overall response rate (ORR).
Evaluated by RECIST v1.1.
Measured: 24months.
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: 24months.
Efficacy endpoints: Progression free survival (DoR).
Evaluated by RECIST v1.1.
Measured: 24months.
Efficacy endpoints: overall survival (OS).
Evaluated by RECIST v1.1
Measured: 24minths
Cmax.
Maximal plasma concentration.
Measured: 24 months.
Tmax.
Time to Cmax.
Measured: 24 months
AUC.
Area under the plasma concentration-time curve.
Measured: 24 months.
t1/2.
Terminal-phase elimination half-life.
Measured: 24 months.
Vz/F.
Apparent volume of distribution during terminal phase after non-intravenous administration.
Measured: 24 months.
CL/F.
Apparent total clearance of the drug from plasma after oral administration.
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 posted9 Sep 2022
- Study start21 Sep 2022
- Primary completion25 Jun 2024
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm study of HRS-4642
- Masking
- None (open label)
- Enrolment
- 102 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
- NCT05533463
- Sponsor's protocol ID
- HRS-4642-I-101
- Status last verified
- Sep 2025
- First submitted
- 5 Sep 2022
- Last updated
- 8 Sep 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Zhou C, Li C, Luo L, Li X, Jia K, He N, Mao S, Wang W, Shao C, Liu X, Huang K, Yu Y, Cai X, Chen Y, Dai Z, Li W, Yu J, Li J, Shen F, Wang Z, He F, Sun X, Mao R, Shi W, Zhang J, Jiang T, Zhang Z, Li F, Ren S. Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer. Cancer Cell. 2024 Jul 8;42(7):1286-1300.e8. doi: 10.1016/j.ccell.2024.06.001. Epub 2024 Jun 27.
PubMed 38942026
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study to Evaluate the Safety ,Tolerability, and Pharmacokinetics of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation
- ClinicalTrials.gov ID
- NCT05533463
- Acronym / sponsor ID
- HRS-4642-I-101
- Conditions
- Advanced KRAS G12D Mutant Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Jiangsu HengRui Medicine Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 21 Sep 2022 (actual)
- Primary completion
- 25 Jun 2024 (actual)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 9 Sep 2022 (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 and tolerability of HRS-4642 in patients with advanced solid tumors harboring KRAS G12D mutation.To estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose [RP2D]) within investigated subject population groups
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm study of HRS-4642
| Arm | Type | Receives |
|---|---|---|
| HRS-4642 | Experimental | Drug: HRS-4642In Dose Escalation: HRS-4642 will be injected QW. Six dose levels are preset. In Dose Expansion: 1 to 2 dose cohorts will be selected for dose expansion stage. In Indication Expansion: Enrollment into the dose expansion cohorts may be from any eligible solid tumor type. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects must voluntarily agree to participate in the trial and sign a written informed consent form.
- Male or female ≥ 18 years old.
- Histologically confirmed diagnosis of advanced solid tumor harbouring with KRAS G12D mutation
- ECOG performance status of 0-1.
- With a life expectancy of ≥3 months.
Key exclusion criteria (8 listed)
- Previously received KRAS G12D inhibitors
- Priot radiotherapy within 28 days for non-thoracic radiation
- Prior anti-tumor chemotherapy (< 6 weeks if chemotherapy including nitrosoureas or mitomycin) within 4 weeks before the study drug administration
- Any unresolved AEs > Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or inclusion/exclusion criteria level (The investigators determined that safe and controllable toxicity was excluded, such as alopecia and ≤ grade 2 peripheral neuropathy ).
- Central nervous system (CNS) metastases
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-4642HRS-4642 will be administrated per dose level in which the patients are assigned. | Drug | HRS-4642 |
Primary outcome
Safety endpoints: adverse events(AEs), serious adverse events（SAEs）.
Time frame: 24 months
Assess safety and tolerability of HRS-4642 by way of adverse events (CTCAE v5.0).
Dose Limited Toxicity(DLT)
Time frame: from day 1 to Day 21
A DLT is defined as any event meeting the DLT criteria occurring within 21 days of first dose on Cycle 1 Day 1 (C1D1), excluding toxicities clearly related to disease progression or intercurrent illness
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 HRS-4642 treatment.
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.
14 secondary outcomes
Number of Participants With Abnormal Laboratory Values
Time frame: 24months.
Number of subjects with clinically significant changes in ECOG, vital signs and physical examination.
Time frame: 24months.
Number of subjects with changes on ECG.
Time frame: 24months.
Efficacy endpoints: Overall response rate (ORR).
Time frame: 24months.
Efficacy endpoints: Duration of response (DoR).
Time frame: 24 months.
Efficacy endpoints: Disease control rate (DCR).
Time frame: 24months.
Efficacy endpoints: Progression free survival (DoR).
Time frame: 24months.
Efficacy endpoints: overall survival (OS).
Time frame: 24minths
Cmax.
Time frame: 24 months.
Tmax.
Time frame: 24 months
AUC.
Time frame: 24 months.
t1/2.
Time frame: 24 months.
Vz/F.
Time frame: 24 months.
CL/F.
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 8 Sep 2025.
- Derived from this study: PubMed 38942026Zhou C, Li C, Luo L, Li X, Jia K, He N, Mao S, Wang W, Shao C, Liu X, Huang K, Yu Y, Cai X, Chen Y, Dai Z, Li W, Yu J, Li J, Shen F, Wang Z, He F, Sun X, Mao R, Shi W, Zhang J, Jiang T, Zhang Z, Li F, Ren S. Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer. Cancer Cell. 2024 Jul 8;42(7):1286-1300.e8. doi: 10.1016/j.ccell.2024.06.001. Epub 2024 Jun 27.
- 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 study testing HRS-4642 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 7 inclusion and 8 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 8 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 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.
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?
Safety endpoints: adverse events(AEs), serious adverse events（SAEs）. (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?
On the ClinicalTrials.gov record for NCT05533463, which also lists 1 linked publication.
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 8 Sep 2025; AzTrials last refreshed its copy on 26 Oct 2026.