Non Small Cell Lung CancerPhase 1NCT04967079
Trametinib Plus Anlotinib in Non-G12C KRAS-Mutant NSCLC Patients
A Phase 1 study testing Trametinib and Anlotinib in people with Non Small Cell Lung Cancer, run by Shanghai Chest Hospital at 1 site in China.
Trial summary
This is a Phase I exploratory study. The study is divided into two parts (A/B).In part A, the primary endpoint is the determination of the recommended phase 2 dose (RP2D). Secondary endpoint for phase Ia includes evaluating the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS)… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Trametinib and Anlotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2021to 26 Mar 2024
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For inclusion in the study subjects should fulfill the following criteria:
- According to the 8th edition of the American Journal of Critical Care (AJCC)/Union for International Cancer Control (UICC) Tumor Node Metastasis (TNM) NSCLC staging system, locally advanced (stage III B/III C), metastatic or recurrent (stage IV) NSCLC patients confirmed by histology or cytology. The NSCLC patient cannot receive surgery and radical radiotherapy, and at least one measurable lesion is confirmed according to RECIST 1.1.
- KRAS mutation positive excluded KRASG12C mutation.
- No active brain metastases.
- Age ≥18 years old and ≤75 years old.
- ECOG PS score: 0-1.
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- Patients who had previously received at least 1st-line standard therapy. Note: the treatment naïve patients who refused immunotherapy/chemotherapy at 1st-line, and willingly enrolled in the clinical trial are also eligible.
- Part A: advanced NSCLC patients with non-G12C mutations who have previously received standard treatment or treatment naïve. Part B: advanced NSCLC patients with non-G12C mutations who have previously received standard 1st or more treatment.
- Palliative radiotherapy must be completed 7 days before the first dose of study drug is administered.
- The main organs are functioning normally, that is, they meet the following standards:
- Good hematopoietic function, defined as absolute neutrophil count ≥1.5 billion
- /L, platelet count ≥100 billion/L, hemoglobin ≥90 g/L [no blood transfusion or no erythropoietin (EPO) within 7 days before enrollment dependence]; The biochemical test results should meet the following standards: BIL <1.25 times the upper limit of normal (ULN); ALT and AST <2.5×ULN; if liver metastasis occurs, ALT and AST <5×ULN; Cr ≤1.5×ULN or creatinine clearance Rate (CCr) ≥60 ml/min; good coagulation function, International Normalized Ratio (INR) and PT ≤1.5 times of ULN; if the subject is receiving anticoagulation therapy, PT should be within the prescribed range of anticoagulation drugs; Women of childbearing age should agree to take contraceptive measures (such as intrauterine devices, contraceptives, or condoms) during the study and within 6 months after the study; the serum or urine pregnancy test of non-breastfeeding patients should be negative; male patients should agree to take contraceptive measures during the study period and within 6 months after the study.
- The patients voluntarily participated in the study, signed an informed consent form and had good compliance.
- The expected survive time is longer than 3 months.
Who cannot join
- Subjects must not enter the study if any of the following exclusion criteria are fulfilled:
- Patients with active central nervous system metastasis are excluded. If a subject has received adequate treatment for central nervous system (CNS) metastasis at least 2 weeks before enrollment, and is neurologically restored to baseline levels (except for residual signs or symptoms related to CNS treatment), the subject is eligible. In addition, subjects must stop corticosteroids, or the daily dose of prednisone must be stabilized orgradually reduced to ≤10 mg (or equivalent dose).
- Small cell lung cancer (including mixed small cell and non-small cell lung cancer) or hollow central squamous cell carcinoma.
- There are obvious bleeding symptoms.
- Patients who have previously received MEK inhibitors, anlotinib or other multi-targeted anti-angiogenic therapy.
- Patients with dysphagia, gastrointestinal resection, chronic diarrhea, intestinal obstruction and other factors that affect oral medication.
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- Patients who are known to have active brain metastases, spinal cord compression, cancerous meningitis, brain or soft tissue diseases diagnosed by computed tomography (CT) or magnetic resonance imaging (MRI) at the time of screening.
- Patients with severe and/or uncontrollable diseases, such as: unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months, severe uncontrollable arrhythmia; uncontrolled blood pressure (BP, constriction BP > 140 mmHg, diastolic BP > 90 mmHg).
- Active or uncontrolled serious infections.
- Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis.
- Incomplete control of eye inflammation or eye infection, or any condition that may cause the above eye diseases.
- Poor diabetes control (fasting blood glucose (FBG) > 10 mmol/L).
- Routine urine test results show that urine protein is ≥++, and the 24-hour urine protein quantitative is> 1.0 g.
- Active tuberculosis.
- Uncontrollable hypercalcemia (calcium ion> 1.5 mmol/L or calcium> 12 mg/dL or corrected serum calcium >ULN), or symptomatic hypercalcemia that requires continued bisphosphonate therapy.
- Long-term unhealed wounds or fractures.
- Those who have a history of psychotropic drug abuse and cannot be quit or have mental disorders.
- Patients with known severe allergies (≥Grade 3) to active ingredients and excipients.
- Patients who also suffer from other malignant tumors (except radical cervical carcinoma in situ, non-melanoma skin cancer, etc.); patients who have been assessed by the investigator as having concomitant diseases that seriously endanger the patient's safety or affect the patient's completion of the study.
- During the clinical trial, the subjects or their sexual partners cannot or refuse to take effective contraceptive measures.
- Pregnant or breastfeeding women.
- Previous treatment including Chinese medicine treatment.
- Patients who are allergic to any medicine or any ingredient.
- In other cases, patients who are not eligible for inclusion as assessed by the investigator.
- The expected survive time is shorter than 3 months.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Combined MEK Inhibitor Trametinib and RTK Inhibitor Anlotinib Therapy in Non-G12C KRAS-Mutant Non-Small Cell Lung Cancer Patients
This is a Phase I exploratory study. The study is divided into two parts (A/B).In part A, the primary endpoint is the determination of the recommended phase 2 dose (RP2D). Secondary endpoint for phase Ia includes evaluating the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and adverse events (AEs). Following the establishment of the RP2D, the expansion cohort will be initiated.
Transitioning to part B, 20 patients will be enrolled to further evaluate the ORR. All patients will receive the trametinib plus anlotinib regimen based on the RP2D determined in part A. The primary endpoint for part B is to assess the ORR, while secondary endpoint includes evaluating PFS, overall survival (OS), DCR, AEs, and duration of overall response (DoR).
Read more
In part A, the study plans to enroll eligible patients to receive the MEK inhibitor trametinib (2 mg) in combination with anlotinib (6mg, 8 mg, 10 mg, 12 mg). The number of subjects is determined according to the actual situation of dose climbing.
In part B, another 20 eligible patients will be enrolled and treated with trametinib (2mg) + anlotinib (RP2D), until the disease progression (PD) or unacceptable toxicity occurs to further evaluate the safety, tolerability and efficacy.
Patients participated in safety follow-up after the first course of treatment until 3 months after discontinuation due to PD or toxicity. Dose-limiting toxicities from the first cycle were collected. Therapeutic efficacy evaluation was scheduled according to RECIST version 1.1 every 4-8 weeks. After the investigators' evaluation, the assessment cycle could extend to 12 weeks or longer due to the uncontrollable factors during the treatment period. Blood samples will be collected for pharmacokinetic analysis and biomarker discovery at baseline and at each periodic assessment.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Trametinib, Anlotinib
- Keywords
- non-G12C KRAS Mutations, Advanced NSCLC, MEK inhibitor-trametinib, RTKs inhibitor-Anlotinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrametinibDrug
Trametinib 2 mg given orally, once daily
AnlotinibDrug
Anlotinib given orally, every two weeks followed by a one-week discontinuation cycle
| Study group | Role | What they receive |
|---|---|---|
| Trametinib + Anlotinib | Experimental | Anlotinib given orally, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) plus trametinib 2 milligrams (mg) given orally, once daily. Receives: Drug: Trametinib; Drug: Anlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Recommended phase 2 dose (RP2D)
The determination of RP2D relied on several priority indexes: firstly, the MTD, followed by ORR, and mean tumor shrinkage rate. If the highest dose of anlotinib (12 mg) did not reach MTD, ORR would be the main index for defining the RP2D. Subsequently, if 2 or more dosage groups had same ORR, the average tumor shrinkage rate would replace MTD and ORR in determining RP2D.
Measured: 1 year
Part B: Objective response rate (ORR)
Percentage of participants achieving CR and PR.
Measured: 1.5 year
Secondary outcomes (5)
Progression Free Survival (PFS)
The time from the start of systemic treatment date to the date of first documented disease progression (event: disease progression - DP, based on RECIST, death, adverse events, which provide to disqualification from further therapy).
Measured: 2 years
Disease control rate (DCR)
Percentage of participants achieving CR and PR and SD.
Measured: 2 years
Overall survival (OS)
OS defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive.
Measured: 2 years
Adverse Event (AE)
Adverse event caused by the combination treatments.
Measured: 2 years
Duration of overall response (DoR)
The time from date of the first documentation of objective response (CR or PR) to the first documentation of PD or to death due to any cause in the absence of documented PD.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2021
- Study start1 Aug 2021
- Primary completion1 Jul 2023
- Study completion26 Mar 2024
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 Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Shanghai Chest HospitalThe 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
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shanghai Chest Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Baohui Han, Shanghai Chest Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04967079
- Sponsor's protocol ID
- ATRAS-LC
- Status last verified
- Apr 2024
- First submitted
- 5 Jul 2021
- Last updated
- 23 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lu J, Hu M, Zhao Y, Chu T, Zhang W, Zhou Y, Cai X, Wu J, Hu L, Shi C, Xiong L, Gu A, Wang H, Zhang Y, Lou Y, Zhong R, Gao Z, Liu H, Zhou C, Wu Y, Zhu L, Zhong H, Ji H, Han B. Coinhibition of the MEK/RTK pathway has high therapeutic efficacy in KRAS-mutant non-small cell lung cancer. Signal Transduct Target Ther. 2025 Sep 12;10(1):299. doi: 10.1038/s41392-025-02382-w.
PubMed 40935839
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined MEK Inhibitor Trametinib and RTK Inhibitor Anlotinib Therapy in Non-G12C KRAS-Mutant Non-Small Cell Lung Cancer Patients
- ClinicalTrials.gov ID
- NCT04967079
- Acronym / sponsor ID
- ATRAS-LC
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- non-G12C KRAS Mutations, Advanced NSCLC, MEK inhibitor-trametinib, RTKs inhibitor-Anlotinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Shanghai Chest HospitalUniversity, hospital or other
- Study start
- 1 Aug 2021 (actual)
- Primary completion
- 1 Jul 2023 (actual)
- Study completion
- 26 Mar 2024 (actual)
- First posted
- 19 Jul 2021 (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 I exploratory study. The study is divided into two parts (A/B).In part A, the primary endpoint is the determination of the recommended phase 2 dose (RP2D). Secondary endpoint for phase Ia includes evaluating the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and adverse events (AEs). Following the establishment of the RP2D, the expansion cohort will be initiated.
Transitioning to part B, 20 patients will be enrolled to further evaluate the ORR. All patients will receive the trametinib plus anlotinib regimen based on the RP2D determined in part A. The primary endpoint for part B is to assess the ORR, while secondary endpoint includes evaluating PFS, overall survival (OS), DCR, AEs, and duration of overall response (DoR).
In part A, the study plans to enroll eligible patients to receive the MEK inhibitor trametinib (2 mg) in combination with anlotinib (6mg, 8 mg, 10 mg, 12 mg). The number of subjects is determined according to the actual situation of dose climbing.
In part B, another 20 eligible patients will be enrolled and treated with trametinib (2mg) + anlotinib (RP2D), until the disease progression (PD) or unacceptable toxicity occurs to further evaluate the safety, tolerability and efficacy.
Patients participated in safety follow-up after the first course of treatment until 3 months after discontinuation due to PD or toxicity. Dose-limiting toxicities from the first cycle were collected. Therapeutic efficacy evaluation was scheduled according to RECIST version 1.1 every 4-8 weeks. After the investigators' evaluation, the assessment cycle could extend to 12 weeks or longer due to the uncontrollable factors during the treatment period. Blood samples will be collected for pharmacokinetic analysis and biomarker discovery at baseline and at each periodic assessment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trametinib + Anlotinib | Experimental | Drug: Trametinib, Drug: AnlotinibAnlotinib given orally, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) plus trametinib 2 milligrams (mg) given orally, once daily. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- For inclusion in the study subjects should fulfill the following criteria:
- Part A: advanced NSCLC patients with non-G12C mutations who have previously received standard treatment or treatment naïve. Part B: advanced NSCLC patients with non-G12C mutations who have previously received standard 1st or more treatment.
- Good hematopoietic function, defined as absolute neutrophil count ≥1.5 billion
- /L, platelet count ≥100 billion/L, hemoglobin ≥90 g/L [no blood transfusion or no erythropoietin (EPO) within 7 days before enrollment dependence]; The biochemical test results should meet the following standards: BIL <1.25 times the upper limit of normal (ULN); ALT and AST <2.5×ULN; if liver metastasis occurs, ALT and AST <5×ULN; Cr ≤1.5×ULN or creatinine clearance Rate (CCr) ≥60 ml/min; good coagulation function, International Normalized Ratio (INR) and PT ≤1.5 times of ULN; if the subject is receiving anticoagulation therapy, PT should be within the prescribed range of anticoagulation drugs; Women of childbearing age should agree to take contraceptive measures (such as intrauterine devices, contraceptives, or condoms) during the study and within 6 months after the study; the serum or urine pregnancy test of non-breastfeeding patients should be negative; male patients should agree to take contraceptive measures during the study period and within 6 months after the study.
Key exclusion criteria (25 listed)
- Subjects must not enter the study if any of the following exclusion criteria are fulfilled:
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 |
|---|---|---|
| TrametinibTrametinib 2 mg given orally, once daily | Drug | Trametinib + Anlotinib |
| AnlotinibAnlotinib given orally, every two weeks followed by a one-week discontinuation cycle | Drug | Trametinib + Anlotinib |
Primary outcome
Part A: Recommended phase 2 dose (RP2D)
Time frame: 1 year
The determination of RP2D relied on several priority indexes: firstly, the MTD, followed by ORR, and mean tumor shrinkage rate. If the highest dose of anlotinib (12 mg) did not reach MTD, ORR would be the main index for defining the RP2D. Subsequently, if 2 or more dosage groups had same ORR, the average tumor shrinkage rate would replace MTD and ORR in determining RP2D.
Part B: Objective response rate (ORR)
Time frame: 1.5 year
Percentage of participants achieving CR and PR.
5 secondary outcomes
Progression Free Survival (PFS)
Time frame: 2 years
Disease control rate (DCR)
Time frame: 2 years
Overall survival (OS)
Time frame: 2 years
Adverse Event (AE)
Time frame: 2 years
Duration of overall response (DoR)
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2024.
- Derived from this study: PubMed 40935839Lu J, Hu M, Zhao Y, Chu T, Zhang W, Zhou Y, Cai X, Wu J, Hu L, Shi C, Xiong L, Gu A, Wang H, Zhang Y, Lou Y, Zhong R, Gao Z, Liu H, Zhou C, Wu Y, Zhu L, Zhong H, Ji H, Han B. Coinhibition of the MEK/RTK pathway has high therapeutic efficacy in KRAS-mutant non-small cell lung cancer. Signal Transduct Target Ther. 2025 Sep 12;10(1):299. doi: 10.1038/s41392-025-02382-w.
- Individual participant dataSharing planned: No
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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 Trametinib and Anlotinib in people with Non Small Cell Lung Cancer, run by Shanghai Chest Hospital 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 14 inclusion and 25 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: finished, as of the sponsor's last update on 23 Apr 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Part A: Recommended phase 2 dose (RP2D) (time frame: 1 year). The study lists 2 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 NCT04967079, 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 23 Apr 2024.