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KRAS Mutation-Related TumorsPhase 1/2NCT06456138

Trametinib Plus Anlotinib Combined With Tislelizumab in KRAS-mutant NSCLC

A Phase 1/2 study testing Trametinib, Anlotinib and Tislelizumab in people with KRAS Mutation-Related Tumors and Advanced Lung Cancer, run by Shanghai Chest Hospital at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

Lung cancer is the most common cause of cancer-related death worldwide. Approximately 85% to 90% of lung cancer cases are non-small cell lung cancer (NSCLC), of which KRAS is one of the most common driver genes, occurring in 25-30% of lung adenocarcinomas and 3-5% of squamous cell carcinomas. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Trametinib, Anlotinib and Tislelizumab
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteChina
Study dates
1 Jul 2024to 31 Dec 2028
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

  • According to the 8th edition of the AJCC/UICC TNM staging system for NSCLC, patients with locally advanced (stage III B/III C), metastatic or recurrent (stage IV) NSCLC confirmed by histology or cytology who are unable to undergo surgery and radical concomitant radiochemotherapy and are confirmed to have at least one measurable lesion according to RECIST 1.1.
  • KRAS mutation positive detected by ARMS or NGS;
  • Have been treated with 1st line of standard therapy and experienced disease progression;
  • Patients who were assessed as CR, PR, or SD (reduction) after being treated with 2 cycles of anlotinib and trametinib.
  • No active brain metastases;
  • Age ≥18 years and ≤75 years;
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  • ECOG PS score: 0 to 2;
  • Palliative radiotherapy must be completed 7 days before the first dose of study drug is administered;
  • The main organs function is normal, that is, the following criteria met:
  • Good hematopoietic function, defined as absolute neutrophil count ≥1.5×10^9 /L, platelet count≥100 ×10^9 /L, hemoglobin ≥90g/L [no blood transfusion or no erythropoietin (EPO) dependence within 7 days before enrollment]
  • Biochemical test results should meet the following criteria: BIL < 1.25 times the upper limit of normal value (ULN); ALT and AST < 2.5 × ULN; in case of liver metastases, ALT and AST < 5 × ULN; Cr ≤1.5×ULN or creatinine clearance (CCr) ≥60ml/min; Coagulation function is good, INR and PT ≤1.5 times ULN; if the subject is receiving anticoagulant treatment, PT should be within the prescribed range of use of anticoagulant drugs;
  • Women of child-bearing age should agree to take contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the study and within 6 months after the study; non-breast-feeding patients whose serum or urinary pregnancy test should be negative; male patients should agree to take contraceptive measures during the study and within 6 months after the study.
  • Patients are voluntarily enrolled into the study, sign the informed consent form and have good compliance.

Who cannot join

  • Small cell lung cancer (including mixed small cell and non-small cell lung cancer);
  • Patients who have received previous treatment ≥ 4th lines of standard therapies.;
  • There are obvious bleeding symptoms or active autoimmune disease;
  • Patients with other driver mutation.
  • Patients with many factors affecting oral medication, such as dysphagia, gastrointestinal resection, chronic diarrhea and intestinal obstruction;
  • Patients who are known to have active brain metastases, spinal cord compression, carcinomatous meningitis, or brain or leptomeningeal disease diagnosed by CT or MRI at the time of screening;
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  • Patients with severe and / or uncontrolled diseases, such as:
  • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months before randomization, severe uncontrolled arrhythmias; uncontrolled blood pressure (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg);
  • Active or uncontrolled serious infection;
  • Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis;
  • Not completely controlled eye inflammation or eye infection, or any condition that may lead to the above-mentioned ocular diseases
  • Poorly controlled diabetes (fasting blood glucose (FBG) > 10mmol/L);
  • Routine urine test result indicates that urine protein ≥++, and 24-hour urine protein quantitation is confirmed to be > 1.0 g;
  • Active tuberculosis, etc.;
  • Uncontrolled hypercalcemia (> 1.5 mmol/L calcium ion or calcium > 12 mg/dL or corrected serum calcium > ULN), or symptomatic hypercalcemia requiring continued diphosphate therapy;
  • Long-term unhealed wounds or fractures;
  • Patients who have a history of psychotropic drug abuse and cannot abstain from it or have mental disorders;
  • Patients who are known to have severe allergies (≥ grade 3) to active ingredients and any excipients of study drugs;
  • Patients who have other malignant tumors (except radical cervical carcinoma in situ, non-melanoma skin cancer, etc.) at the same time; patients who are evaluated by the investigator to have concomitant diseases that seriously endanger the safety of the patients or affect the patients completing the study.
  • The subjects or their sexual partners cannot or refuse to take effective contraceptive measures during the clinical trial.
  • Pregnant or breast-feeding women.
  • Patients who are allergic to any medicine or any ingredient; the patients with a history of treatments involving MEK inhibitors (trametinib, selumetinib, etc.) and RTKs inhibitors (anlotinib, sorafenib, apatinib, cabozantinib, etc.) were considered ineligible.
  • Patients in other situations who are evaluated by the investigator to be ineligible to be enrolled.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Tianqing Chu, MD, PhD contact

+86 13661775640

ctqxkyy@163.com

Jun Lu, MD, PhD contact

+86 2122200000

lujun512@yahoo.com

China1 site

  • Shanghai Chest Hospital

    Shanghai

    Baohui Han, MD, PhD, +86 18930858216, 18930858216@163.com

    Jun Lu, MD, PhD, +86 13601887656, lujun512@yahoo.com

Other trials in China

About this study

Official title: Trametinib Plus Anlotinib Combined With Tislelizumab in KRAS-mutant Advanced Non-small Cell Lung Cancer Patients: a Multi-center, Open-label, Phase 1/2 Study

Lung cancer is the most common cause of cancer-related death worldwide. Approximately 85% to 90% of lung cancer cases are non-small cell lung cancer (NSCLC), of which KRAS is one of the most common driver genes, occurring in 25-30% of lung adenocarcinomas and 3-5% of squamous cell carcinomas. KRAS-mutant NSCLC had been considered undruggable in past decades. This research sought to address a significant challenge in treating NSCLC with KRAS mutations, which are notoriously difficult to target effectively. Here, we proposal that the combined use of anlotinib and trametinib combined with tislelizumab may form an effective strategy for the treatment of KRAS-mutant NSCLC patients.

Read the detailed description

This is a phase 1/2, open-label, multi-center study aimed at exploring the potential therapeutic efficacy of tislelizumab (intravenous), trametinib (oral) and anlotinib (oral) in KRAS-mutant advanced non-small cell lung cancer patients. The primary objectives were safety, recommended phase 2 dose (RP2D) in Phase I and PFS in Phase II. The secondary aim of the study is to evaluate the progression-free survival (PFS), overall survival (OS), adverse events (AEs), and duration of response (DOR) of the combined strategy in these patients. If the RP2D is reached in Phase I, Phase II will be started; if RP2D is not reached in Phase I, Phase II will not be started. The number of subjects is determined according to the actual situation of dose climbing. All patients will be of histo- and/or cytopathology confirmed. Determination of the KRAS mutation type will be performed in the pathological department of Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine. Both ARMS method or targeted sequencing are acceptable. It is not acceptable for subjects with the presence of other driver gene mutation. All eligible subjects must have adequate renal, hepatic, and hematologic function, as defined in "inclusion criteria".

Keywords
KRAS-mutant NSCLC, Trametinib, Anlotinib, Tislelizumab
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TrametinibDrug

    Trametinib will be administrated orally every day.

  • AnlotinibDrug

    Anlotinib will be administrated orally from day 1 to day 14 per 21-day cycle.

  • TislelizumabDrug

    Tislelizumab will be administered at full dose (200mg, Q3W) on the patient who received the efficacy evaluation of stable disease (SD) or partial response (PR) or complete response (CR) after 2 cycles' treatment of trametinib plus anlotinib.

Study groups in NCT06456138
Study groupRoleWhat they receive
Trametinib + Anlotinib + TislelizumabExperimentalIn Phase I, there are four treatment arms: anlotinib (6 mg) plus trametinib (1 mg) plus tislelizumab (200 mg, Q3W), anlotinib (6 mg) plus trametinib (2 mg) plus tislelizumab (200 mg, Q3W), anlotinib (8 mg) plus trametinib (1 mg) plus tislelizumab (200 mg, Q3W), and anlotinib (8 mg) plus trametinib (2 mg) plus tislelizumab (200 mg, Q3W). In Phase II, there is one treatment arm including trametinib (RP2D) plus anlotinib (RP2D) plus tislelizumab (200 mg, Q3W).
Receives: Drug: Trametinib; Drug: Anlotinib; Drug: Tislelizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. RP2D

    recommended phase 2 dose

    Measured: up to 12 months

  2. PFS

    progression-free survival

    Measured: up to 18 months

Secondary outcomes (4)

  1. ORR

    objective response rate

    Measured: up to 12 months

  2. OS

    overall survival

    Measured: up to 24 months

  3. DOR

    duration of response

    Measured: up to 18 months

  4. AEs

    adverse events

    Measured: up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jun 2024
  2. Study start1 Jul 2024 (estimated)
  3. Primary completion30 Jun 2026 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06456138
Sponsor's protocol ID
ATT-RAS-001
Status last verified
Jun 2024
First submitted
5 Jun 2024
Last updated
13 Jun 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Trametinib, Anlotinib and Tislelizumab in people with KRAS Mutation-Related Tumors and Advanced 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 13 inclusion and 23 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: opening soon, as of the sponsor's last update on 13 Jun 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 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?

Contact Tianqing Chu, MD, PhD (+86 13661775640, ctqxkyy@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

RP2D (time frame: up to 12 months). 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 NCT06456138.

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 13 Jun 2024.

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