Tislelizumab Combined With Chemotherapy With or Without Bevacizumab in TKI-Resistant EGFR-Mutated Non-squamous NSCLC

NCT04405674 | Unknown Phase 2

• 1 other identifier: BGB-A317-2001-IIT
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

A phase II, open-label, multicenter, two cohorts, prospective clinical study to investigate the efficacy and safety of tislelizumab (anti-pd1 antibody) combined with chemotherapy with or without bevacizumab in non-squamous non-small cell lung cancer patients with EGFR sensitizing mutation who failed EGFR TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) therapy.

Conditions

Non Small Cell Lung Cancer

Keywords

Tislelizumab; PD-1; Chemotherapy; EGFR mutation; Non small cell lung cancer; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• 1-Year Progression-Free Survival Rate (1-Year PFS Rate)

  Progression-free survival (per RECIST 1.1) is defined as the time from the starting date of study drug to the date of first documentation of disease progression or death, whichever occurs first. Subjects who do not have disease progression will be censored at their last valid tumor assessment. PFS rate at 1 year as estimated by Kaplan-Meier method.

  up to 24 months after enrollment or study close

Secondary Outcomes (5)

• Progression-Free Survival (PFS)

  up to 24 months after enrollment or study close

• Objective Respond Rate (ORR)

  up to 24 months after enrollment or study close

• Disease Control Rate (DCR)

  up to 24 months after enrollment or study close

• Overall Survival (OS)

  up to 24 months after enrollment or study close

• Duration of Response (DoR)

  up to 24 months after enrollment or study close

Study Arms (2)

Tislelizumab plus chemotherapy

EXPERIMENTAL

Tislelizumab plus Carboplatin/Nab-paclitaxel as induction treatment and followed by Tislelizumab plus pemetrexed as maintenance treatment.

Drug: Tislelizumab; Drug: Carboplatin; Drug: Pemetrexed; Drug: Nab paclitaxel

Tislelizumab plus chemotherapy plus Bevacizumab

EXPERIMENTAL

Tislelizumab plus Nab-paclitaxel and Bevacizumab as induction treatment and followed by Tislelizumab plus Bevacizumab as maintenance treatment.

Drug: Tislelizumab; Drug: Bevacizumab; Drug: Nab paclitaxel

Interventions

Tislelizumab DRUG

Tislelizumab 200mg administered intravenously (IV) on Day 1 of each 21-day cycle

Also known as: BGB-A317

Tislelizumab plus chemotherapy; Tislelizumab plus chemotherapy plus Bevacizumab

Carboplatin DRUG

Carboplatin AUC 5 administered intravenously (IV) on Day 1 of each 21-day cycle, 4 cycles

Tislelizumab plus chemotherapy

Pemetrexed DRUG

Pemetrexed 500mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle

Tislelizumab plus chemotherapy

Bevacizumab DRUG

Bevacizumab 7.5mg/kg administered intravenously (IV) on Day 1 of each 21-day cycle

Tislelizumab plus chemotherapy plus Bevacizumab

Nab paclitaxel DRUG

Nab-paclitaxel 260mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle, 4 cycles

Tislelizumab plus chemotherapy; Tislelizumab plus chemotherapy plus Bevacizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed, locally advanced (Stage IIIB/C) not amenable to curative surgery or radiotherapy, or metastatic (Stage IV) non-squamous NSCLC according to American Joint Committee on Cancer, 8th Edition.
• Documentation of tumor EGFR sensitizing mutation before EGFR TKI treatment, including 19del, L858R, G719X, S786I and L861Q.
• Disease progression after treatment with an EGFR TKI therapy: 1) Patients previously treated with 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib/icotinib) are required to provide specimens after PD to confirmed absence of EGFR T790M mutation; 2) Patients with confirmed acquired T790M mutation after 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib/icotinib) are required to have 3rd generation EGFR TKI (e.g. osimertinib) treatment failure prior to enrollment; 3) Patients previously failed from 3rd generation EGFR TKI (e.g. osimertinib) treatment as 1st line therapy are eligible regardless of their EGFR T790M mutation status.
• ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1.
• Life expectancy ≥ 3 months.
• Adequate organ function
• Able to provide written informed consent by the patient or by the patient's legally acceptable representative and can understand and agree to comply with the requirements of the study.
• to 75 years old on the day of signing the ICF (Informed Consent Form).

You may not qualify if:

• Received prior therapies targeting PD-1, PD-L1, CTLA-4 or other immune checkpoints.
• Received prior platinum-based chemotherapy for advanced disease.
• Patients who have received prior systemic anti-vascular therapy (e.g., bevacizumab and small molecule VEGFR inhibitors) for advanced disease (Cohort 2)
• Received EGFR TKI treatment within 2 weeks
• Treatment with any approved systemic anti-cancer therapy or systemic immune-stimulatory agents (including but not limited to interferons, interleukin IL-2, and tumor necrosis factor) within 28 days prior to initiation of study treatment.
• Clinically uncontrolled pleural effusion or ascites that requires pleurocentesis or abdominal tapping for drainage within 2 weeks prior to initiation of study treatment.
• Active leptomeningeal disease or uncontrolled brain metastasis.
• History of allergic reactions to any study drugs.
• CrCl \< 45 mL/min
• Patients with active viral hepatitis that requires treatment.
• Active autoimmune diseases that requires treatment and may affect study treatment estimated by investigator.
• Any condition that required systemic treatment with either corticosteroids or any other immunosuppressive medication that may affect study treatment estimated by investigator.
• Severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy.
• History of hemoptysis, i.e., coughing up at least one-half teaspoon of fresh blood, within 3 months prior to enrollment. (Cohort 2)
• Imaging shows tumor invasion of a large vessel (e.g., pulmonary artery or superior vena cava) that the investigator determines is at risk for bleeding. (Cohort 2)

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

tislelizumab; Carboplatin; Pemetrexed; Bevacizumab; Taxes

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Economics; Health Care Economics and Organizations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Director of Pulmonary Medicine at Shanghai Chest Hospital

Study Record Dates

• First Submitted: May 25, 2020
• First Posted: May 28, 2020
• Study Start: July 15, 2020
• Primary Completion: April 1, 2022
• Study Completion: March 1, 2025
• Last Updated: November 22, 2021

Record last verified: 2021-11

Locations

CN (1)