NCT04507906

Nivolumab Combined With Anlotinib as Re-challenge Treatment in Advanced NSCLC

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: Shanghai Chest Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Conditions

• NSCLC Stage IV
• Checkpoint Inhibitor

Interventions

Type	Name	Description
DRUG	Nivolumab Combined with Anlotinib	In combination dose finding phase, Phase 1b will begin with Dose Level 1; anlotinib 12 mg/day orally (from days 1 to 14 in a 21-day cycle) and nivolumab (360mg q3w, intravenously) will be administered to eligible subjects on a 21-day treatment cycle. Two dose de-escalation steps are included: Dose Level 2 (anlotinib 10 mg/day orally, from days 1 to 14 in a 21-day cycle) and nivolumab 360mg q3w, intravenously) and Dose Level 3 (anlotinib 8 mg/day orally, from days 1 to 14 in a 21-day cycle) and nivolumab 360mg q3w, intravenously).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) .

Timeline

• Start date: 2020-11-02
• Primary completion: 2022-03-31
• Completion: 2022-03-31
• First posted: 2020-08-11
• Last updated: 2022-06-28

Locations

1 site across 1 country: China

Regulatory

• FDA-regulated drug study