Advanced or Metastatic Solid TumorPhase 1NCT05263986
The Clinical Trial to Evaluate the Pharmacokinetics and Safety of MRTX849 in Patients With Advanced Solid Tumors
A Phase 1 study testing MRTX849 in people with Advanced or Metastatic Solid Tumor, run by Zai Lab (Shanghai) Co., Ltd. at 8 sites in China.
Trial summary
This is a phase 1, open-label, single-arm study in Chinese patients with unresectable, locally advanced or metastatic solid tumor with KRAS G12C mutation, for which treatment with curative intent is not available. Patients must have a documented KRAS G12C mutation determined by tissue or liquid-based local testing. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic Solid Tumor
- What is being tested?
- MRTX849
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 8 sitesChina
- Study dates
- 30 May 2022to 31 Oct 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- 1. Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation.
- 2. Unresectable or metastatic disease.
- 3. Available therapy:
- no available treatment with curative intent,
- no available standard-of-care treatment or patient is ineligible or declines treatment.
- 4. Presence of measurable or non-measurable disease per RECIST 1.1.
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- 5. Age ≥ 18 years.
- 6. Life expectancy of at least 3 months.
- 7. Most recent prior systemic therapy (e.g., chemotherapy, immunotherapy, or investigational agent) and radiation therapy discontinued at least 2 weeks before first dose date.
- 8. Recovery from the adverse effects of prior therapy at the time of enrollment to ≤ Grade 1 (excluding alopecia).
- 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- 10. Laboratory values within the ranges below during the screening period:
- <!-- -->
- Absolute neutrophil count ≥ 1,000/mm3 (≥ 1.0 x 109/L)
- Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L)
- Hemoglobin ≥ 9 g/dL, in the absence of transfusions for at least 2 weeks
- Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) (if associated with liver metastases or Gilbert's disease, ≤ 3 x ULN)
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN (if associated with liver metastases, ≤ 5 x ULN)
- Creatinine clearance (CrCl) ≥ 60 mL/min.
- 11. Women of childbearing potential (WOCBP) or men whose partner is a WOCBP agree to use contraception while participating in this study, and for a period of 6 months following termination of study treatment.
- 12. Completed informed consent process, including signing Ethics Committee (EC)-approved informed consent form.
- 13. Willing to comply with clinical trial instructions and requirements.
Who cannot join
- 1. Use of the treatment known to cause prolonged corrected QT interval (QTc) or with a known risk of Torsades de Pointes that cannot be switched to alternative treatment within 5 half-lives prior to MRTX849 dosing initiation
- 2. Use of any drugs or substances including herbal supplements known or suspected to alter MRTX849 absorption, distribution, metabolism, or excretion:
- Inhibitors of CYP3A4, CYP2C8, P-glycoprotein (P-gp), or breast cancer resistance protein (BCRP) within 7 days or 5 half-lives, whichever is longer, prior to MRTX849 dosing initiation.
- Inducers of CYP3A4 or CYP2C8 within 14 days or 5 half-lives, whichever is longer, prior to MRTX849 dosing initiation.
- Proton-pump inhibitors within 7 days or 5 half-lives, whichever is longer, prior to MRTX849 dosing initiation.
- 3. Active brain metastases or carcinomatous meningitis. Patients are eligible if brain metastases are adequately treated and patients are neurologically stable for at least 2 weeks prior to study entry without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
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- 4. History of significant hemoptysis or hemorrhage within 4 weeks prior to MRTX849 dosing initiation.
- 5. Any of the following cardiac abnormalities:
- <!-- -->
- Unstable angina pectoris or myocardial infarction within 6 months prior to
- MRTX849 dosing initiation.
- Symptomatic or uncontrolled atrial fibrillation within 6 months prior to
- MRTX849 dosing initiation.
- Congestive heart failure ≥ New York Heart Association (NYHA) Class 3 within 6 months prior to MRTX849 dosing initiation.
- Prolonged QTc interval > 480 milliseconds.
- 6. History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow oral medications.
- 7. Known human immunodeficiency virus (HIV) infection or acute or chronic hepatitis B or C infection. Note that the following are permitted:
- <!-- -->
- Patients treated for hepatitis C (HCV) with no detectable viral load;
- Patients treated for HIV with no detectable viral load for at least 1 month prior to study entry while on a stable regimen of agents that are not strong inhibitors of CYP3A4; and
- Patients with hepatitis B (HBV) receiving prophylaxis against reactivation of hepatitis B (either [HBsAg-positive with normal ALT and HBV DNA <2,000 IU/mL or <10,000 copies/mL] or [HBsAg-negative and anti-HBc-positive]).
- 8. Major surgery within 4 weeks prior to MRTX849 dosing initiation.
- 9. History of stroke or transient ischemic attack within 6 months prior to MRTX849 dosing initiation.
- 10. Known or suspected presence of another malignancy that could be mistaken for the malignancy under study during disease assessments.
- 11. Pregnancy. WOCBP must have a negative serum or urine pregnancy test documented within the screening period prior to MRTX849 dosing initiation.
- 12. Breast-feeding or planning to breast feed during the study or within 6 months after study treatment with MRTX849.
- 13. Any serious illness, uncontrolled intercurrent illness, psychiatric illness, active or uncontrolled infection, or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with the patient's participation in the study, or with the interpretation of the results.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
China8 sites
Beijing Cancer Hospital
Beijing, Beijing Municipality
The first Hospital of Jilin University
Changchun, Jilin
Hunan Cancer Hospital
Changsha, Hunan
Chongqing University Cancer Hospital
Chongqing, Chongqing Municipality
Lin Yi Cancer Hospital
Linyi, Shandong
Shanghai Chest Hospital
Shanghai, Shanghai Municipality
Union hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei
Henan Cancer Hospital
Zhengzhou, Henan
About this study
Official title: A Phase 1, Open-label, Single-arm Study to Evaluate the Pharmacokinetics and Safety of MRTX849 in Chinese Patients With Advanced Solid Tumors With KRAS G12C Mutation
This is a phase 1, open-label, single-arm study in Chinese patients with unresectable, locally advanced or metastatic solid tumor with KRAS G12C mutation, for which treatment with curative intent is not available.
Patients must have a documented KRAS G12C mutation determined by tissue or liquid-based local testing.
Read more
The PK profile of MRTX849 in Chinese patients will be evaluated after administration of a single and repeat oral doses of 600 mg BID. In the PK lead-in period, blood samples will be collected pre-dose and up to 96 hours post a single oral dose of 600 mg MRTX849. Following this lead-in period, patients will start the dosing regimen of 600 mg BID orally, and blood samples will be collected pre-dose and up to 12 hours after multiple doses of MRTX849 600 mg BID on Cycle 1 Day 8 (C1D8).
Safety including AEs, ECGs, laboratory parameters and vital signs of each patient will be monitored throughout the conduct of the study.
Disease response and progression will be evaluated in accordance with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
- Conditions
- Advanced or Metastatic Solid Tumor
- Being tested
- MRTX849
- Keywords
- KRAS G12C mutation
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRTX849Drug
Approximately 18-24 patients to ensure at least 12 PK evaluable patients.
Subjects will be administered a single oral dose of 600 mg MRTX849 in PK lead in D1, and will start the dosing regimen of 600 mg BID orally from C1D1.
| Study group | Role | What they receive |
|---|---|---|
| Assigned Interventions | Experimental | In the 5-day PK lead-in period, patients will receive a single oral dose of 600 mg MRTX849 on Day 1 and there will be no drug administration in the subsequent 4 days. Following the PK lead-in period, patients will receive MRTX849 600 mg BID (an interval of approximate 12 hours between 2 doses) orally in 3-week cycles until disease progression, unacceptable AEs, patient refusal, or death. Dosing schedules may be adjusted depending on safety results. Receives: Drug: MRTX849 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Main PK parameters: Cmax
Maximum plasma concentration (Cmax) after single dose
Measured: Approximately 2 weeks after dose initiation
Main PK parameters: Tmax
Maximum plasma concentration (Tmax) after single dose
Measured: Approximately 2 weeks after dose initiation
Main PK parameters: AUC0-12
Area under the concentration-time curve from time 0 to 12 hours (AUC0-12) after single dose
Measured: Approximately 12 hours after dose initiation
Main PK parameters: AUC0-t
Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-t) after single dose
Measured: Approximately 2 weeks after dose initiation
Main PK parameters: AUC0-∞
Area under the concentration-time curve from time 0 to infinity (AUC0-∞) after single dose
Measured: Approximately 2 weeks after dose initiation
Main PK parameters: t1/2
Terminal half-life (t1/2) after single dose
Measured: Approximately 2 weeks after dose initiation
Main PK parameters: CL/F
Apparent clearance (CL/F) after single dose
Measured: Approximately 2 weeks after dose initiation
Main PK parameters: Vz/F
Apparent volume of distribution associated with the terminal phase (Vz/F) after single dose
Measured: Approximately 2 weeks after dose initiation
Main PK parameters: Cmax, ss
Maximum plasma concentration at steady state (Cmax, ss)
Measured: Approximately 2 weeks after dose initiation
Main PK parameters: Tmax, ss
Time to observed maximum plasma concentration at steady state (Tmax, ss)
Measured: Approximately 2 weeks after dose initiation
Main PK parameters: Cmin, ss
Trough concentration (Cmin, ss)
Measured: Approximately 2 weeks after dose initiation
Main PK parameters: Cavg
Average concentration during a dosing interval (Cavg)
Measured: Approximately 2 weeks after dose initiation
Main PK parameters: AUCss
Area under the concentration-time curve at steady state (AUCss)
Measured: Approximately 2 weeks after dose initiation
Main PK parameters: Rac for Cmax and AUCtau
Accumulation ratio (Rac for Cmax and AUCtau)
Measured: Approximately 2 weeks after dose initiation
Main PK parameters: PTR
Peak-to-trough ratio (PTR)
Measured: Approximately 2 weeks after dose initiation
Secondary outcomes (5)
Incidence of Treatment-Emergent Adverse Events
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0
Measured: Approximately 12 months after dose initiation
Incidence of Treatment-Emergent Serious Adverse Events
Incidence of Treatment-Emergent Serious Adverse Events as assessed by CTCAE v5.0
Measured: Approximately 12 months after dose initiation
Incidence of Treatment-Related Adverse Events
Incidence of Treatment-Related Adverse Events as assessed by CTCAE v5.0
Measured: Approximately 12 months after dose initiation
Incidence of Treatment-Related Serious Adverse Events
Incidence of Treatment-Related Serious Adverse Events as assessed by CTCAE v5.0
Measured: Approximately 12 months after dose initiation
Incidence of abnormal laboratory value
Incidence of abnormal laboratory value is defined as the proportion of patients who have abnormal laboratory value not prior to the dose initiation of MRTX849
Measured: Approximately 12 months after dose initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2022
- Study start30 May 2022
- Primary completion31 Oct 2023 (estimated)
- Study completion31 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic Solid TumorStudies of the same condition, open and under way.
- 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
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zai Lab (Shanghai) Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Mirati Therapeutics Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05263986
- Sponsor's protocol ID
- ZL-2312-005
- Status last verified
- Feb 2023
- First submitted
- 13 Jan 2022
- Last updated
- 27 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Single-arm Study to Evaluate the Pharmacokinetics and Safety of MRTX849 in Chinese Patients With Advanced Solid Tumors With KRAS G12C Mutation
- ClinicalTrials.gov ID
- NCT05263986
- Acronym / sponsor ID
- ZL-2312-005
- Conditions
- Advanced or Metastatic Solid Tumor
- Keywords
- KRAS G12C mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Zai Lab (Shanghai) Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Mirati Therapeutics Inc.
- Study start
- 30 May 2022 (actual)
- Primary completion
- 31 Oct 2023 (estimated)
- Study completion
- 31 Oct 2023 (estimated)
- First posted
- 3 Mar 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.
This is a phase 1, open-label, single-arm study in Chinese patients with unresectable, locally advanced or metastatic solid tumor with KRAS G12C mutation, for which treatment with curative intent is not available.
Patients must have a documented KRAS G12C mutation determined by tissue or liquid-based local testing.
The PK profile of MRTX849 in Chinese patients will be evaluated after administration of a single and repeat oral doses of 600 mg BID. In the PK lead-in period, blood samples will be collected pre-dose and up to 96 hours post a single oral dose of 600 mg MRTX849. Following this lead-in period, patients will start the dosing regimen of 600 mg BID orally, and blood samples will be collected pre-dose and up to 12 hours after multiple doses of MRTX849 600 mg BID on Cycle 1 Day 8 (C1D8).
Safety including AEs, ECGs, laboratory parameters and vital signs of each patient will be monitored throughout the conduct of the study.
Disease response and progression will be evaluated in accordance with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Assigned Interventions | Experimental | Drug: MRTX849In the 5-day PK lead-in period, patients will receive a single oral dose of 600 mg MRTX849 on Day 1 and there will be no drug administration in the subsequent 4 days. Following the PK lead-in period, patients will receive MRTX849 600 mg BID (an interval of approximate 12 hours between 2 doses) orally in 3-week cycles until disease progression, unacceptable AEs, patient refusal, or death. Dosing schedules may be adjusted depending on safety results. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 1. Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation.
- 2. Unresectable or metastatic disease.
- 4. Presence of measurable or non-measurable disease per RECIST 1.1.
- 5. Age ≥ 18 years.
- 6. Life expectancy of at least 3 months.
Key exclusion criteria (27 listed)
- 1. Use of the treatment known to cause prolonged corrected QT interval (QTc) or with a known risk of Torsades de Pointes that cannot be switched to alternative treatment within 5 half-lives prior to MRTX849 dosing initiation
- 2. Use of any drugs or substances including herbal supplements known or suspected to alter MRTX849 absorption, distribution, metabolism, or excretion:
- 3. Active brain metastases or carcinomatous meningitis. Patients are eligible if brain metastases are adequately treated and patients are neurologically stable for at least 2 weeks prior to study entry without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
- 4. History of significant hemoptysis or hemorrhage within 4 weeks prior to MRTX849 dosing initiation.
- <!-- -->
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 |
|---|---|---|
| MRTX849Approximately 18-24 patients to ensure at least 12 PK evaluable patients. Subjects will be administered a single oral dose of 600 mg MRTX849 in PK lead in D1, and will start the dosing regimen of 600 mg BID orally from C1D1. | Drug | Assigned Interventions |
Primary outcome
Main PK parameters: Cmax
Time frame: Approximately 2 weeks after dose initiation
Maximum plasma concentration (Cmax) after single dose
Main PK parameters: Tmax
Time frame: Approximately 2 weeks after dose initiation
Maximum plasma concentration (Tmax) after single dose
Main PK parameters: AUC0-12
Time frame: Approximately 12 hours after dose initiation
Area under the concentration-time curve from time 0 to 12 hours (AUC0-12) after single dose
Main PK parameters: AUC0-t
Time frame: Approximately 2 weeks after dose initiation
Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-t) after single dose
Main PK parameters: AUC0-∞
Time frame: Approximately 2 weeks after dose initiation
Area under the concentration-time curve from time 0 to infinity (AUC0-∞) after single dose
Main PK parameters: t1/2
Time frame: Approximately 2 weeks after dose initiation
Terminal half-life (t1/2) after single dose
Main PK parameters: CL/F
Time frame: Approximately 2 weeks after dose initiation
Apparent clearance (CL/F) after single dose
Main PK parameters: Vz/F
Time frame: Approximately 2 weeks after dose initiation
Apparent volume of distribution associated with the terminal phase (Vz/F) after single dose
Main PK parameters: Cmax, ss
Time frame: Approximately 2 weeks after dose initiation
Maximum plasma concentration at steady state (Cmax, ss)
Main PK parameters: Tmax, ss
Time frame: Approximately 2 weeks after dose initiation
Time to observed maximum plasma concentration at steady state (Tmax, ss)
Main PK parameters: Cmin, ss
Time frame: Approximately 2 weeks after dose initiation
Trough concentration (Cmin, ss)
Main PK parameters: Cavg
Time frame: Approximately 2 weeks after dose initiation
Average concentration during a dosing interval (Cavg)
Main PK parameters: AUCss
Time frame: Approximately 2 weeks after dose initiation
Area under the concentration-time curve at steady state (AUCss)
Main PK parameters: Rac for Cmax and AUCtau
Time frame: Approximately 2 weeks after dose initiation
Accumulation ratio (Rac for Cmax and AUCtau)
Main PK parameters: PTR
Time frame: Approximately 2 weeks after dose initiation
Peak-to-trough ratio (PTR)
5 secondary outcomes
Incidence of Treatment-Emergent Adverse Events
Time frame: Approximately 12 months after dose initiation
Incidence of Treatment-Emergent Serious Adverse Events
Time frame: Approximately 12 months after dose initiation
Incidence of Treatment-Related Adverse Events
Time frame: Approximately 12 months after dose initiation
Incidence of Treatment-Related Serious Adverse Events
Time frame: Approximately 12 months after dose initiation
Incidence of abnormal laboratory value
Time frame: Approximately 12 months after dose initiation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2023.
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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.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MRTX849 in people with Advanced or Metastatic Solid Tumor, run by Zai Lab (Shanghai) Co., Ltd. at 8 sites 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 22 inclusion and 27 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: status not confirmed, as of the sponsor's last update on 27 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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?
Results are not available in the source record.
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?
Main PK parameters: Cmax (time frame: Approximately 2 weeks after dose initiation). The study lists 15 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 27 Feb 2023.