Study of Tislelizumab for Locally Advanced Non-Small Cell Lung Cancer Following Neoadjuvant Chemotherapy Plus Tislelizumab ± Bevacizumab and Definitive Concurrent Chemoradiation Therapy

NCT ID: NCT05468242

Last Updated: 2024-10-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-01
• Study Completion Date: 2024-12-30

Brief Summary

The phase II Study is to explore the efficacy and safety of Tislelizumab as consolidation therapy in patients with locally advanced non-small cell lung cancer who have not progressed following neoadjuvant chemotherapy plus Tislelizumab ± Bevacizumab and definitive concurrent chemoradiation therapy.

Conditions

Stage III Non-small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant Chemotherapy Plus Tislelizumab + Bevacizumab

Patients in experimental group will receive Tislelizumab consolidation (200 mg/q3w) after the neoadjuvant chemotherapy plus Tislelizumab + Bevacizumab and concurrent chemoradiotherapy.

Group Type: EXPERIMENTAL

Neoadjuvant chemo-immunotherapy

Intervention Type: DRUG

The neoadjuvant chemo-immunotherapy before radiotherapy comprised of chemotherapy plus Tislelizumab \[200 mg, once every 3 weeks (Q3W)\].

Bevacizumab

Intervention Type: DRUG

The Bevacizumab was administrated concurrently with neoadjuvant chemo-immunotherapy (7.5mg/kg) once every 3 weeks (Q3W).

Radiotherapy

Intervention Type: RADIATION

Definitive radiotherapy to the thoracic lesions.

Tislelizumab

Intervention Type: DRUG

Tislelizumab consolidation (200 mg) is performed once every 3 weeks after the neoadjuvant therapy and concurrent chemo-radiotherapy, and will continue on a Q3W schedule for a maximum duration of 12 months.

Neoadjuvant Chemotherapy Plus Tislelizumab

Patients in this group will receive Tislelizumab consolidation (200 mg/q3w) after the neoadjuvant chemotherapy plus Tislelizumab and concurrent chemoradiotherapy.

Group Type: ACTIVE_COMPARATOR

Neoadjuvant chemo-immunotherapy

Intervention Type: DRUG

The neoadjuvant chemo-immunotherapy before radiotherapy comprised of chemotherapy plus Tislelizumab \[200 mg, once every 3 weeks (Q3W)\].

Radiotherapy

Intervention Type: RADIATION

Definitive radiotherapy to the thoracic lesions.

Tislelizumab

Intervention Type: DRUG

Tislelizumab consolidation (200 mg) is performed once every 3 weeks after the neoadjuvant therapy and concurrent chemo-radiotherapy, and will continue on a Q3W schedule for a maximum duration of 12 months.

Interventions

Neoadjuvant chemo-immunotherapy

The neoadjuvant chemo-immunotherapy before radiotherapy comprised of chemotherapy plus Tislelizumab \[200 mg, once every 3 weeks (Q3W)\].

Intervention Type: DRUG

Bevacizumab

The Bevacizumab was administrated concurrently with neoadjuvant chemo-immunotherapy (7.5mg/kg) once every 3 weeks (Q3W).

Intervention Type: DRUG

Radiotherapy

Definitive radiotherapy to the thoracic lesions.

Intervention Type: RADIATION

Tislelizumab

Tislelizumab consolidation (200 mg) is performed once every 3 weeks after the neoadjuvant therapy and concurrent chemo-radiotherapy, and will continue on a Q3W schedule for a maximum duration of 12 months.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• For inclusion in neoadjuvant therapy, patients should fulfil the following criteria:

• Provision of signed, written and dated informed consent prior to any study specific procedures;
• Male or female aged 18~75 years old;
• Patients must have histologically- or cytologically-documented NSCLC who present with locally advanced (Stage III) disease;
• Without prior chemotherapy, radiotherapy, surgery, targeted therapy or immunotherapy;
• A recent tumour biopsy (taken following completion of the most recent therapy) is an optional requirement, provided that a biopsy procedure is technically feasible and the procedure is not associated with unacceptable clinical risk;
• Life expectancy ≥12 weeks;
• World Health Organization (WHO) Performance Status of 0 or 1;
• Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients within 14 days before the use of study drug (HCG has a minimum sensitivity of 25 IU/L or equivalent);
• Women must be non-breastfeeding
• Forced expiratory volume in 1 second (FEV1) ≥800ml
• Absolute neutrophil count >1.5 x 109/L (1500 per mm3)
• Platelets >100 x 109/L (100,000 per mm3)
• Haemoglobin≥9.0 g/dL (5.59 mmol/L)
• Serum creatinine clearance(CL) >50 mL/min by the Cockcroft-Gault formula (Cockcroft and -Gault 1976)
• Serum bilirubin ≤1.5 x upper limit of normal (ULN). Aspartate Transaminase(AST) and Alanine Transaminase(ALT) ≤2.5 x ULN

Exclusion Criteria

• Concurrent enrolment in another clinical study, unless it is an observational(non-interventional) clinical study;
• Mixed small cell and non-small cell lung cancer histology;
• Current or prior use of immunosuppressive medication within 28 days before the first dose of Tislelizumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for NSCLC is allowed.
• Prior exposure to any anti-programmed cell death protein(PD)-1 or anti-PD-L1 antibody;
• Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of Tislelizumab;
• Active or prior documented autoimmune disease within the past 2 years;
• Active or prior documented inflammatory bowel disease (eg. Crohn's disease, ulcerative colitis);
• History of primary immunodeficiency;
• History of organ transplant that requires therapeutic immunosuppression;
• The tumor has completely approached, encircled, or invaded the intravascular space of the great vessels (e.g., the pulmonary artery or the superior vena cava)
• Bleeding tendency or coagulation disorder
• Hypertensive crisis, hypertensive encephalopathy, symptomatic heart failure (New York class II or above), active cerebrovascular disease or cardiovascular disease occurred within 6 months
• Uncontrolled hypertension (systolic > 150mmHg and/or diastolic > 100mmHg)
• Major surgery within 28 days or minor surgery or needle biopsy within 48 hours
• Urine protein 3-4+, or 24h urine protein quantitative >1g
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Bazett's Correction;
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent;
• Known history of tuberculosis;
• Receipt of live attenuated vaccination within 30 days prior to study entry or within30 days of receiving Tislelizumab;
• History of another primary malignancy within 5 years prior to starting Tislelizumab, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study;
• Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control;
• Any condition that, in the opinion of the investigator, would interfere with evaluation of the Tislelizumab or interpretation of patient safety or study results.

• Patients who develop disease progression and the irradiation dose of normal tissue will exceed the limit as defined in Section 7.
• World Health Organization (WHO) Performance Status of 2-4;
• Inadequate organ and marrow function as defined below:
• Forced expiratory volume in 1 second (FEV1) <800ml
• Absolute neutrophil count <1.5 x 109/L (1500 per mm3)
• Platelets <100 x 109/L (100,000 per mm3)
• Haemoglobin<9.0 g/dL (5.59 mmol/L)
• Serum creatinine CL <50 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976)
• Serum bilirubin >1.5 x upper limit of normal (ULN).
• Aspartate Transaminase(AST) and Alanine Transaminase(ALT) >2.5 x ULN

• Patients who have progressed whilst definitive platinum based, concurrent chemoradiation therapy;
• Current or prior use of immunosuppressive medication within 28 days before the first dose of Tislelizumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed.
• Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy will be excluded from randomization;
• Patients with Grade ≥2 pneumonitis from prior chemoradiation therapy will be excluded from randomization; Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE>Grade 1.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Hui Liu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hui Liu

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-sen University

Guangzhou, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Bo Qiu, MD

Role: CONTACT

qiubo@sysucc.org.cn

+86-020-87343031

DaQuan Wang, MD

Role: CONTACT

wangdq@sysucc.org.cn

+86-020-87343031

Facility Contacts

Hui Liu, Professor

Role: primary

liuhui@sysucc.org.cn

+86-020-87343031

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Other Identifiers

GASTO-1086

Identifier Type: -

Identifier Source: org_study_id