Evaluate the Efficacy and Safety of Ensartinib and Bevacizumab in Patients With Advanced, ALK-Rearranged Combined With TP53 Mutation, Non-Small Cell Lung Cancer: A Prospective, Open-label, Multi-center, Single-arm, Phase II Trial
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Sun Yat-sen University
- Enrollment
- 58
- Locations
- 1
- Primary Endpoint
- 12-month Progression-free Survival (PFS) rate
Overview
Brief Summary
This is a prospective, single-arm, multicenter, phase II study to investigate the efficacy and safety of Ensartinib plus Bevacizumab in metastatic anaplastic lymphoma kinase (ALK)-rearranged Non-Small Cell Lung Cancer (NSCLC) with TP53 mutation.
Detailed Description
Patients with advanced or metastatic NSCLC with ALK positive and TP53 mutation were clinically confirmed. Medical history collection, physical examination, laboratory examination, concomitant diseases and medication records were taken according to the patient's diagnosis and treatment. Laboratory examination included but not limited to blood routine and blood biochemical examination. To determine whether patients were suitable for treatment with Ensartinib combined with Bevacizumab according to the entry and exclusion criteria. For patients who met the prescription, blood samples were collected within 1 week before medication. Imaging examination was performed every 6 weeks (±7 days) in the first 2 years and every 12 weeks (±7 days) in the second 2 years. Examination items included chest CT, head MRI; See if additional tests (e.g., bone scan, total abdominal augmentation) are needed based on the actual clinical situation. When the disease progresses, blood samples should be collected within 4 weeks after the disease progression, and if possible, tumor tissues of the progressive lesions after the disease progression should be collected. Patients can choose to continue to use the regimen recommended by the doctor if the doctor considers that the use of Ensartinib therapy or combination therapy may still bring benefit to the patient. The follow-up treatment plan, the best efficacy evaluation, and the duration of treatment were recorded. When the end point of follow-up was reached, that is, the patient died or was lost to follow-up, the date of death or loss and the main causes should be tracked and recorded in detail.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically or cytologically confirmed advanced (stage IIIB) or metastatic (stage IV) NSCLC;
- •ALK positive with TP53 mutation was confirmed by tissue samples or blood in each center; TP53 mutation detection needs to be confirmed by NGS. ALK positive can be detected by NGS,IHC,RT-PCR and FISH;
- •Age ≥ 18 years old;
- •ALK-TKI-naive patients, and allowed to have received at most one line previous chemotherapy;
- •ECOG Performance status (PS) score is 0-2;
- •Karnofsky Performance Status of ≥70;
- •Subjects with CNS metastases are only eligible if the CNS metastases are adequately treated with radiotherapy and/or surgery and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 1 week prior to randomization.
- •A.Patients receiving radiotherapy or radiosurgery with a dose exceeding 30 Gy will have 3 weeks for neurological stabilization before randomization.
- •B.This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- •Life expectancy of at least 12 weeks;
Exclusion Criteria
- •Only ALK positive or TP53 mutation;
- •Patients who have received any previous ALK-TKI treatment;
- •Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 \[L858R\] substitution mutations) are excluded. All subjects with non-squamous histology must have been tested locally for EGFR mutation status; use of an FDA-approved test is strongly encouraged (EGFR mutation testing may be performed during the Screening Period, Non-squamous subjects with unknown or indeterminate EGFR status may not be included);
- •Subjects with untreated CNS metastases are excluded;
- •Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period;
- •Active hepatitis B (serum HBV DNA≥1.0E+4 copies /ml\[i.e. 2,000 IU/ml\]), positive for hepatitis C virus antibody, HIV antibody, and treponema pallidum antibody;
- •Women of childbearing age who had a positive serum pregnancy test 7 days before the start of treatment, women who were pregnant or lactating, or male and female subjects who did not take effective contraceptive measures or planned to have children during the whole treatment period and 3 months after the end of treatment;
- •Patients who have used any of the following drugs within 14 days before the first dose or need to combine them during treatment: drugs at risk for prolonged QTc and/or torsive-tip ventricular tachycardia; CYP3A strong inhibitor or strong inducer;
- •Major surgery or immunotherapy was performed within 4 weeks before the first dose; He received radiotherapy within 2 weeks before the first dose.
- •Imaging (CT or MRI) showed that the tumor invaded the great blood vessels or it was judged that the tumor was very likely to invade the important blood vessels and cause fatal massive bleeding during the subsequent study
Arms & Interventions
Ensartinib and Bevacizumab
Ensartinib 225 mg oral once daily with Bevacizumab 7.5mg/kg intravenous every 3 weeks
Intervention: Ensartinib (Drug)
Ensartinib and Bevacizumab
Ensartinib 225 mg oral once daily with Bevacizumab 7.5mg/kg intravenous every 3 weeks
Intervention: Bevacizumab (Drug)
Outcomes
Primary Outcomes
12-month Progression-free Survival (PFS) rate
Time Frame: The primary analysis of 12-month PFS rate based on investigator assessment will occur when PFS maturity is observed at approximately 12 months after the first patient begin study treatment
Progression-free survival (PFS) using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Progression-free survival (PFS) is defined as the time from beginning of study treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable Response Evaluation Criteria in Solid Tumors (RECIST) assessment.
Secondary Outcomes
- Disease-related symptom improvement(12 weeks since treatment start)
- Disease Control Rate (DCR)(through study completion, an average of 12 months)
- PFS(Through study completion, an average of 18 months)
- Objective Response Rate (ORR)(8 weeks)
- Duration of Response (DoR)(12 months)
- Overall Survival (OS)(Through study completion, an average of 18 months)
Investigators
Li Zhang, MD
Professor
Sun Yat-sen University