NCT07463677
Not yet recruiting
Phase 2
A Study Protocol for Evaluating the Efficacy and Safety of Tunlametinib Combination Therapy in KRAS-Mutated Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Sun Yat-sen University0 sites55 target enrollmentStarted: March 15, 2026Last updated:
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Sun Yat-sen University
- Enrollment
- 55
- Primary Endpoint
- Objective Response Rate (ORR)
Overview
Brief Summary
This study investigated the efficacy and safety of Tunlametinib Combination Therapy in KRAS-Mutated Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Informed consent, all participants will provide written informed consent.
- •Participants older than 18 years of age signed their own informed consent form.
- •The TNM staging was classified according to the 8th edition of the AJCC Cancer Staging Manual of the American Joint Committee on Cancer (AJCC). Eligible patients had histologically or cytologically confirmed unresectable, locally advanced, or metastatic NSCLC9(IIIB、IIIC、IV).
- •Eligible patients had failed, were intolerant to first-line standard treatment after diagnosis.
- •Positive for KRAS driver gene mutations (including: KRAS G12C and KRAS non-G12C).
- •Patients were required to have at least 1 site of disease that qualified as a measurable (target) lesion by RECIST v1.1 (If the lesion at the previous radiotherapy site is selected as the target lesion, there is a clear evidence of progression of this lesion).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •The functions of the major organs meet the following requirements, and no blood transfusion or use of hematopoietic stimulating factor drugs has been conducted within 14 days prior to the relevant examination: 1) Thrombocytopenia（PLT）≥100×109/L； 2) Blood hemoglobin（HGB）≥90g/L； 3) neutrophil count（NEUT）≥1.5×109/L； 4) creatinine ≤1.5×ULN or Creatinine clearance（CrCl）≥50 mL/min（was calculated using the Modification of CockroftGaul）； 5) alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤2.5×ULN（If the patient has liver metastasis ≤5×ULN）； 6) total bilirubin level（TBIL）≤1.5×ULN（Patients with Gilbert's syndrome may receive ≤3×ULN.）；If direct bilirubin (DBIL) indicates extrahepatic obstruction, then TBIL \< 3.0 × ULN is permissible； 7) International normalized ratio（INR）or prothrombin time（PT）≤1.5×ULN，activated partial thromboplastin time（APTT）≤1.5×ULN，Patients whose bleeding tendency is assessed by the researchers as controllable 8) The urine protein creatinine ratio had to be 2+ or less, or the 24-hour urine protein had to be less than 1,000 mg, for patient enrollment.
- •The life expectance should be at least 3 months.
- •Eligible patients of child-bearing age (men and women) agreed to take effective contraceptive measures (including hormonal contraception, barrier methods, or abstinence) during the study period and for at least 6 months after the last study drug administration.
Exclusion Criteria
- •Subjects had received anticancer drugs or investigational drugs within the following time window: 1) Any KRAS G12C mutation inhibitor within 3 years prior to the first dose in this study, including but not limited to Sotorasib (AMG510), Adagrasib (MRTX849), IBI351 (GFH925), Glecirasib (JAB-21822), JDQ443, LY3537982, and GDC-6036; 2) Cituximab or its analogues within 3 years prior to the first dose of this study; 3) Prior MEK inhibitor therapy; 4) Any anticancer therapy (including chemotherapy, targeted therapy, immunotherapy, etc.) or any other investigational drug within 28 days prior to the first dose of this study; 5) Received traditional Chinese patent medicines with explicit antitumor indications in NMPA-approved drug labels within 2 weeks prior to the first dose of this study (including Compound Mylabris Capsules, Kang'ai Injection, Kanglaite Capsules/Injection, Aidi Injection, Yadanzi Oil Injection/ capsules, Xiaoaiping tablets/injection, Huachansu capsules, etc.) within 28 days prior to receiving any anticancer therapy (including chemotherapy, targeted therapy, immunotherapy, etc.) or any other investigational drug therapy in this study; and 6) Received known CYP2D6, CYP3A4, P-gp, and BCRP sensitive substrates with narrow therapeutic windows within 14 days prior to study dosing or within 5 drug half-lives (whichever is longer), unless the participants are approved for inclusion by the researchers and all parties involved..
- •NSCLC with other driver gene mutations that have standard treatment drugs (such as EGFR, ALK, BRAF(V600E), HER-2, MET(exon14), ROS1, RET or NTRK1/2/3, etc.) in the past.
- •Concurrent primary malignancies are permitted, except in the following circumstances: Other malignancies treated with a single surgical procedure, with complete remission for at least 3 years prior to enrollment; or Untreated basal cell carcinoma or carcinoma in situ (e.g., carcinoma in situ of the skin, breast carcinoma in situ, cervical carcinoma in situ); Prostate cancer requiring only clinical monitoring without treatment.
- •Symptomatic or progressively worsening CNS metastases or carcinomatous meningitis. Subjects with a history of brain metastases may be considered for inclusion if clinically stable, provided they meet all of the following criteria: 1) Absence of neurological symptoms, no requirement for corticosteroid therapy, and no indication for radiotherapy; the largest lesion on the most recent pre-enrollment imaging study must have a maximum diameter ≤1.5 cm. 2) Active CNS metastases (e.g., brain or meningeal metastases) are not eligible for enrollment. For subjects with brain metastases who have undergone radiotherapy or local treatment: - If no corticosteroids or antiepileptic drugs were used, asymptomatic status must be maintained for at least 7 days after radiotherapy completion. - If corticosteroids or antiepileptic drugs were used, symptomatic status must be maintained for at least 7 days after discontinuation, and the investigator must assess brain metastases as stable and controlled. 3) For subjects asymptomatic after CNS radiotherapy, corticosteroids must have been discontinued for at least 2 weeks prior to the first study dose.
- •Cardiovascular system meeting any of the following criteria: 1) Congestive heart failure at New York Heart Association (NYHA) functional class II or higher; 2) Severe arrhythmia requiring medication; 3) Acute myocardial infarction, severe or unstable angina, coronary artery bypass grafting (CABG), or peripheral artery bypass grafting within 6 months prior to enrollment; 4) Left ventricular ejection fraction (LVEF) \<50%; 5) Resting QT interval prolongation (QTcF) as measured by the Fridericia formula, ECG-measured QTcF \> 470 ms in females or \> 450 ms in males, or presence of risk factors for torsades de pointes, such as investigator-assessed clinically significant hypokalemia, family history of long QT syndrome, or familial arrhythmia history (e.g., Wolff-Parkinson-White syndrome); 6) Uncontrolled hypertension (defined as systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg despite standardized antihypertensive therapy);
- •Patients who have experienced arterial or venous thrombotic events within the past 6 months, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, pulmonary embolism, hypertensive crisis, or hypertensive encephalopathy;
- •Patients with a history of seizures were excluded.
- •The superior vena cava.
- •Active non-infectious pneumonia with interstitial changes such as interstitial lung disease, radiation pneumonitis, or immune-related pneumonia during the screening period; active pulmonary tuberculosis; pneumoconiosis; or other types of pneumonia classified as Grade ≥2; or severe impairment of pulmonary function confirmed by pulmonary function tests (FEV1 or DLCO or DLCO/VA \<40% of predicted value).
- •Severe bone damage caused by tumor bone metastases present at baseline or likely to occur after enrollment, such as weight-bearing pathological fractures, extensive bone metastases, or spinal cord compression occurring within 6 months prior to enrollment or likely to occur after enrollment; or uncontrollable pain related to tumor bone metastases;
Arms & Interventions
Arm 1
Experimental
Tunlametinib: 6 mg / 9 mg / 12 mg orally twice daily (BID). Cetuximab β: Administered intravenously at a dose of 500 mg/m² (based on body surface area) once every two weeks.
Each treatment cycle is defined as 4 weeks.
Intervention: Tunlametinib + Cetuximab β (Drug)
Arm 2
Experimental
Arm 2: Tunlametinib: 6 mg / 9 mg / 12 mg orally twice daily (BID). Fluorescein: 600 mg orally twice daily (BID). Each treatment cycle is defined as 4 weeks.
Intervention: Tunlametinib + Fulzerasib (Drug)
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: up to 180 days
Defined as the percentage of subjects achieving complete response (CR) or partial response (PR) as assessed by RECIST 1.1.
Secondary Outcomes
- Progression Free Survival (PFS)(up to 180 days)
- Disease Control Rate (DCR)(up to 180 days)
- Duration of Response (DoR)(up to 180 days)
- Incidence and severity of adverse events (AEs)(30 Days, an average of 3 months)
- Overall Survival (OS)(up to 360 days)
- Time to Response (TTR)(up to 180 days)
Investigators
Li Zhang, MD
Sun Yat-sen University
Sun Yat-sen University
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