Non-small-cell lung cancer
Conditions
Interventions
Group A (Phase I):Dosage A: Ensatinib 225 mg QD each time and Vorolanib 100 mg QD
Group B (Phase I):Dosage B: Ensatinib 225mg QD each time and Vorolanib 200mg QD
Intervention group (Phase II):The dose determinated by Phase I
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Males or females aged between 18 and 75 (inclusive); 2. Histologically or cytologically confirmed as unresectable stage IIIB-IV non-small cell lung cancer (NSCLC); 3. The written report confirms ALK positivity (confirmed by FISH, Ventana IHC, RT-PCR, or NGS) with TP53 mutation (TP53 mutation detection requires confirmation by NGS) (patients enrolled in the Phase I study phase are not considered whether they carry TP53 mutations); 4. Patients who have not undergone any ALK-TKI treatment, and who are also allowed to have received up to one course of postoperative adjuvant chemotherapy in the past, with no disease progression within 6 months; 5. ECOG Physical Status (PS) score is 0-2; 6. Expected lifespan of at least 12 weeks; 7. According to RECIST 1.1 standard, there must be at least one measurable lesion. 8. Capable of swallowing oral medications; 9. Having certain organ system functions, defined as follows, determined based on the researcher's experience (1). Absolute neutrophil count (ANC) >= 1.5 x10^9/L (2). Platelets >= 100 x 10^9/L; (3). Hemoglobin >= 9 g/dL (>= 90g/L). Note that blood transfusion is allowed to achieve the required hemoglobin level; (4). Total bilirubin = 1.5 ULN and the creatinine clearance rate calculated by the Cockcroft Gault method is >= 50 mL/min (0.83 mL/s), the patient still qualifies for inclusion; 10. Female participants of childbearing age must undergo a serum pregnancy test within 3 days before starting the study medication, and the result must be negative. They must also be willing to use a medically recognized and effective contraceptive measure (such as intrauterine device, contraceptive pill, or condom) during the study period and within 3 months after the last administration of the study medication; For male participants whose partners are women of childbearing age, they should agree to use effective contraception methods during the study period and within 3 months after the last study administration. 11. Voluntarily and capable of following the trial and follow-up procedures. 12. Can understand the nature of the experiment and be able to sign a written informed consent form.
Exclusion criteria
Exclusion criteria: 1. Patients with only ALK positivity or TP53 mutation (patients enrolled in Phase I studies are not considered whether they carry TP53 mutation); 2. Patients who have received any ALK-TKI, immunotherapy, or anti vascular drug treatment in the past; 3. Active hepatitis B (serum HBV DNA >= 10^4 copies/ml [i.e. 20000 IU/ml]), hepatitis C virus antibody positive, AIDS virus antibody, syphilis spirochete antibody positive; 4. Women of childbearing age, pregnant or lactating women with positive serum pregnancy test results 7 days before starting treatment, or male and female subjects who have not taken effective contraceptive measures or plan to give birth throughout the treatment period and 3 months after the end of treatment; 5. Patients who have used or require concomitant use of the following medications within 14 days prior to the first administration: medications that pose a risk of QTc prolongation and/or apical torsion type ventricular tachycardia; Strong inhibitors or inducers of CYP3A; 6. Underwent major surgery or immunotherapy within 4 weeks prior to the first administration; Received radiation therapy within 2 weeks prior to the first administration. 7. Imaging (CT or MRI) shows that the tumor has invaded large blood vessels or is highly likely to invade important blood vessels and cause fatal massive bleeding during subsequent studies; 8. Unstable brain metastases with symptoms or requiring steroid treatment within the first 4 weeks of enrollment. Patients with asymptomatic brain metastases or those who have been stable for more than 4 weeks after treatment and do not require steroid therapy can be included in the study, while patients with meningeal metastases will not be included; 9. According to the researcher's opinion, other severe, acute or chronic medical conditions that may increase the risk associated with participating in the study, or may interfere with the interpretation of the study results, including uncontrollable diabetes or medical diseases or mental diseases or laboratory abnormalities; 10. Researchers believe that there are other situations that are not suitable for participating in this experiment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity (Phase I);Maximum tolerated dose (Phase I);Objective Response Rate (Phase II); | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease control rate (Phase II);Progression-free survival (Phase II);Duration of Response (Phase II);Overall survival (Phase II);Adverse event (Phase II); | — |
Countries
China
Contacts
Public ContactTian Panwen
West China Hospital of Sichuan University
Outcome results
None listed