Safety and Efficacy of Nivolumab Combined With Anlotinib in Advanced Non-small Cell Lung Cancer Patients Previously Treated With Checkpoint Inhibitor-A Single Center and Exploratory Study

Shanghai Chest Hospital1 site in 1 country21 target enrollmentNovember 2, 2020

ConditionsNSCLC Stage IV Checkpoint Inhibitor

InterventionsNivolumab Combined with Anlotinib

DrugsNivolumab Combined with Anlotinib

Overview

Phase: Phase 1
Intervention: Nivolumab Combined with Anlotinib
Conditions: NSCLC Stage IV
Sponsor: Shanghai Chest Hospital
Enrollment: 21
Locations: 1
Primary Endpoint: Objective response rate (ORR)
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a phase Ib/IIa, open-label, single center study, aiming to investigate safety and efficacy of nivolumab (administered intravenously) in combination with anlotinib (administered orally) in immunotherapy-treated advanced NSCLC. The study has been designed to allow an investigation of the optimal combination dose and schedule while ensuring the safety of patients with intensive safety monitoring. There are two main parts to this study; Part A, combination dose finding and Parts B, dose expansion. Part B will either be initiated if RP2D reached in Part A, or not initiated if RP2D was not reached in Part A.

Part A has been designed to identify the recommended dose of combination of nivolumab plus anlotinib for further clinical evaluation based upon assessment of the safety and tolerability data collected during the first 21 days (cycle 1, 21 days per cycle). The 21-day assessment period was selected as the major toxicities leading to cessation of dose de-escalation in such Phase I oncology studies (haematological, gastrointestinal, liver enzymes) are anticipated to present within this duration. "3+3"design was used in the dose finding cohort.

If RP2D was reached in Part A, eligible patients would be enrolled and receive nivolumab (360mg q3w, intravenously) plus anlotinib (RP2D, QD from day 1 to 14 of a 21-day cycle) till disease progression (PD) withdraw of consent, or unacceptable toxicity to further evaluate the safety, tolerability and efficacy in terms of ORR , DCR, DOR, PFS and OS. The tumor response will be evaluated according to RECIST Version 1.1 every 6 weeks.

Registry

clinicaltrials.gov

Start Date

November 2, 2020

End Date

March 31, 2022

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Chest Hospital

Responsible Party

Principal Investigator

Baohui Han

Director of pulmonary department of Shanghai Chest Hospital

Shanghai Chest Hospital

Eligibility Criteria

Inclusion Criteria

•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.
•Without active brain metastasis
•Previously treated with ICIs with progressive disease.
•Age ≥18 years and ≤75 years;
•ECOG PS score: 0 to 1
•Palliative radiotherapy must be completed 7 days before the first dose of study drugs;
•The main organs function is normal, that is, the following criteria met:
•Good hematopoietic function, defined as absolute neutrophil count ≥1.5×109 /L, platelet count≥100 ×109 /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.

Exclusion Criteria

•Patients who meet any of the following criteria will be excluded:
•Subjects with active CNS metastases are excluded. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
•Small cell lung cancer (including mixed small cell and non-small cell lung cancer) or central squamous cell carcinoma with cavity;
•With obvious hemorrhage symptom
•With driver mutation (EGFR/ALK/ROS1) or mutation status are unknown
•Patients who have not received IO as frontline treatment;
•Patients who have grade 3 AEs when treated with IO
•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;
•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);