This study is a prospective, multicenter, two-stage phase II clinical trial evaluating the efficacy and safety of Utidelone combined with Bevacizumab in patients with non-small cell lung cancer with brain metastases.
The main objective of the first stage was to determine the combined dose of the first stage and the second stage, and to compare the intracranial efficacy of the two treatment groups. Secondary objectives were to compare other intracranial efficacy, systemic efficacy, safety and tolerability between the two treatment groups.In the second stage, the main purpose was to evaluate the intracranial efficacy of Utidelone combined with Bevacizumab in patients, and the secondary purpose was to evaluate the other intracranial efficacy, systemic efficacy, safety and tolerability of Utidelone combined with Bevacizumab in patients, and to explore the improvement of patients' quality of life.
Informed consent for the study was obtained from the participants and a written informed consent form (ICF) was provided.
age ≥18 years old and ≤70 years old, regardless of gender;
non-squamous non-small cell lung cancer (adenocarcinoma or adenocarcinoma component dominant) with brain parenchymal metastasis confirmed by histology or cytology, but unsuitable or refused local treatment/surgery;
at least one measurable intracranial lesion according to RECIST v1.1 criteria (a lesion previously treated with radiotherapy could not be considered a target lesion unless it had definite progression after radiotherapy);
primary malignant brain tumors and symptomatic or investigator-judged unstable brain metastases; Patients with leptomeningeal metastasis;
mixed adenosquamous carcinoma with squamous cells as the main component confirmed by histology or cytology (squamous cell carcinoma cells accounted for ≥10%);
The presence of EGFR, ALK, ROS1, NTRK and MET driver genes in patients with previous pathology can be determined according to the results of gene detection during the first-line treatment.
Patients without disease progression after whole brain radiotherapy or stereotactic conformal radiotherapy for all intracranial lesions were not eligible for measurable lesions;
Factorial
Utidelone combined with Bevacizumab
DrugThe initial dose was Utidelone 30mg/m2/d,D1-D5,Q3W+ Bevacizumab 15mg/kg/Q3w. If dose adjustment was required due to DLT events, Utidelone was reduced by up to one dose (to 25mg/m2/d), while the dose of Bevacizumab remained unchanged (15mg/kg).
Utidelone
DrugUtidelone injection, 30mg/m2/d, D1-D5 for 5 consecutive days, every 21 days as a treatment cycle
Utidelone combined with Bevacizumab
DrugIn the combination group, the dose of Utidelone was determined according to the safety run-in period, 30 mg/m2/d or 25mg/m2/d, D1-D5,Q3W; The dose of Bevacizumab was 15 mg/kg/3W.
Utidelone combined with Bevacizumab
DrugThe dose of Utidelone was 30 mg/m2/d or 25mg/m2/d, D1-D5,Q3W; The dose of Bevacizumab was 15 mg/kg/3w.
Intracranial objective response rate (iORR) according to the RECIST 1.1.
iORR is defined as the proportion of subjects with a confirmed intracranial response of complete response (CR) and partial response (PR).
Determining the Expansion Dose
The first safety run-in phase was used to determine the dose to be administered in the combination group in the extension phase.
Intracranial progression-free survival (iPFS)
iPFS: defined as time from dose index to intracranial disease progression or death from any cause.
Intracranial disease control rate (iDCR) according to the RECIST 1.1.
iDCR: defined as the proportion of subjects with confirmed intracranial response with CR, PR, and SD.
Objective Response Rate （ORR）according to the RECIST 1.1.
ORR: defined as the proportion of subjects with a confirmed CR and PR.
Disease Control Rate （DCR）according to the RECIST 1.1.
DCR: defined as the proportion of subjects with confirmed CR and PR and SD.
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