First-Line Treatment for Advanced Non-squamous Non-Small-Cell Lung Cancer With Negative Driver Gene: a Single-center, Single-Arm Trial — SPBPDC  

Advanced Non-squamous Non-Small-Cell Lung Cancer Clinical Trial

Official title: Sintilimab Plus Bevacizumab and Platinum-Based Doublet Chemotherapy as First-Line Treatment for Advanced Non-squamous Non-Small-Cell Lung Cancer With Negative Driver Gene: a Single-center, Single-Arm Trial

Status Recruiting

Clinical Trial Summary

To evaluate the efficacy and safety of sintilimab plus bevacizumab and platinum-based doublet chemotherapy as the first-line therapy for advanced nonsquamous non-small-cell lung cancer(NSCLC) with negative driver gene.

This study is an exploratory single-arm study. The specific treatment regimen is as follows:

Non-squamous NSCLC: Sintilimab (200 mg) plus Bevacizumab (7.5mg/kg) is started on the first day of each treatment cycle and administered every three weeks. Nedaplatin (80-100 mg/m2) (d2) +pemetrexed 500 mg/m2 (d2) Q3W is administered in this regimen for 4 cycles followed by sintilimab plus bevacizumab until disease progression or intolerable toxicity.

Patients are assessed for measurable disease at baseline, 6 weeks, 12 weeks after starting treatment, and every 9 weeks thereafter according to RECIST 1.1 criteria during the treatment period until disease progression or intolerable toxicity withdrawal. Following discontinuation of treatment, subjects are followed for survival status every 3 months until death. Subject safety was assessed during treatment according to NCI CTCAE Version 4.0 criteria. Subjects who experience an AE should be followed until the AE returns to baseline. The primary endpoints is Progression-free survival (PFS) . Secondary endpoints include objective response rate (ORR), overall survival (OS) and safety (NCI CTCAE v 4.0). Statistical methods: The PFS curve was estimated using the Kaplan-Meier method for the largest population to be analyzed. The confidence interval method was used as the criterion for the main analysis. OS was calculated in the same way as the secondary endpoint. Descriptive statistics will be used to analyze ORR, DCR, etc. It is expected that sintilimab plus bevacizumab and platinum-based doublet chemotherapy as first-line treatment will prolong median PFS and OS in patients with driver gene-negative advanced Non-squamous NSCLC.

Clinical Trial Description

Lung cancer is the most common cause of cancer mortality worldwide[1]. NSCLC represents more than 80% of lung cancer cases[2], with most having nonsquamous histology[3].Current first-line treatment options in metastatic nonsquamous NSCLC without oncogenic driver alterations include checkpoint inhibitor monotherapy in patients with high programmed death-ligand 1 (PD-L1) expression and checkpoint inhibitor therapy in combination with platinum-doublet chemotherapy with or without bevacizumab[4.5].Despite the available standard-of-care first-line treatments, clinical outcomes have remained suboptimal and additional therapeutic options are needed.

Sintilimab is a recombinant, fully human IgG4 anti-PD-1 monoclonal antibody. Preclinical data have shown that sintilimab has a greater affinity against PD-1 than pembrolizumab or nivolumab[6].In a randomised, double-blind, phase 3 trial, sintilimab plus chemotherapy resulted in significantly longer progression-free survival and overall survival versus chemotherapy alone in patients with treatment-naive NSCLC without EGFR or ALK genomic tumour mutations, with a manageable safety profile[7.8].

Bevacizumab, in addition to its known anti-angiogenic effects, has immunomodulatory effects through inhibition of vascular endothelial growth factor (VEGF), including promotion of dendritic cell maturation; normalisation of the tumour vasculature, which might increase T-cell infiltration; and reprogramming of the tumour microenvironment from being immune suppressive to immune permissive[9.10]. Therefore, reversal of VEGF-mediated immunosuppression by bevacizumab could enhance the antitumour activity of sintilimab.

We aimed to evaluate the efficacy and safety of sintilimab with bevacizumab plus platinum-based doublet chemotherapy for the treatment of patients with driver gene-negative advanced nonsquamous NSCLC.

Objective: To evaluate the efficacy and safety of sintilimab plus bevacizumab and platinum-based doublet chemotherapy as the first-line therapy for advanced nonsquamous non-small-cell lung cancer with negative driver gene.

The research idea starts from the safety and efficacy of sintilimab plus bevacizumab and platinum-based doublet chemotherapy for NSCLC. Under the theoretical perspective of clinical research on cancer treatment, an exploratory single-center single-arm study method is used to perform sintilimab plus bevacizumab and platinum-based doublet chemotherapy regimen for first-line treatment of advanced nonsquamous NSCLC patients with negative driver gene. A database is established for the enrolled case report form, systematic data analysis is performed, and finally the study conclusions of above treatment safety and efficacy are obtained. It is expected that sintilimab plus bevacizumab and platinum-based doublet chemotherapy as first-line treatment will prolong median PFS and OS in patients with driver gene-negative advanced nonsquamous NSCLC.

This study is an exploratory single-arm study. The specific treatment regimen is as follows :Non-squamous NSCLC: Sintilimab (200 mg) plus Bevacizumab (7.5mg/kg) is started on the first day of each treatment cycle and administered every three weeks. Nedaplatin (80-100 mg/m2) (d2) +pemetrexed 500 mg/m2 (d2) Q3W is administered in this regimen for 4 cycles followed by sintilimab plus Bevacizumab until disease progression or intolerable toxicity.

Patients are assessed for measurable disease at baseline, 6 weeks, 12 weeks after starting treatment, and every 9 weeks thereafter according to RECIST1.1 criteria during the treatment period until disease progression or intolerable toxicity withdrawal. Following discontinuation of treatment, subjects are followed for survival status every 3 months until death. Subject safety was assessed during treatment according to NCI CTCAE Version 4.0 criteria. Subjects who experience an AE should be followed until the AE returns to baseline. The primary endpoints is Progression-free survival (PFS) . Secondary endpoints include objective response rate (ORR), overall survival (OS) and safety (NCI CTCAE v 4.0).

Statistical methods: The PFS curve was estimated using the Kaplan-Meier method for the largest population to be analyzed. The confidence interval method was used as the criterion for the main analysis. OS was calculated in the same way as the secondary endpoint. Descriptive statistics will be used to analyze ORR, DCR, etc. ;

Related Conditions & MeSH terms

• Advanced Non-squamous Non-Small-Cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

• NCT number: NCT05648071
• Study type: Interventional
• Source: Qianfoshan Hospital
• Contact: Degan Lu, professor
• Phone: 18753157623
• Email: deganlu@126.com
• Status: Recruiting
• Phase: Phase 3
• Start date: December 1, 2021
• Completion date: July 1, 2025