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

Stage III Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase II Trial 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05468242
• Other study ID #: GASTO-1086
• Status: Recruiting
• Phase: Phase 2
• Start date: January 1, 2022
• Est. completion date: December 30, 2024

Study information

• Verified date: December 2023
• Source: Sun Yat-sen University
• Contact: Bo Qiu, MD
• Phone: +86-020-87343031
• Email: qiubo[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 116
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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:

• Exclusion criteria for enrolment for neoadjuvant therapy Patients should not enter the

study if any of the following exclusion criteria are fulfilled:

• 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.
• Exclusion criteria for concurrent chemoradiation following neoadjuvant therapy Patients should not enter the concurrent chemoradiation phase if any of the following

exclusion criteria are fulfilled:

• 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
• Further exclusion criteria for Tislelizumab consolidation:

Patients should not enter the Tislelizumab consolidation if any of the following exclusion

criteria are fulfilled:

• 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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Stage III Non-small Cell Lung Cancer

Intervention

Drug:
• Neoadjuvant chemo-immunotherapy
The neoadjuvant chemo-immunotherapy before radiotherapy comprised of chemotherapy plus Tislelizumab [200 mg, once every 3 weeks (Q3W)].
• Bevacizumab
The Bevacizumab was administrated concurrently with neoadjuvant chemo-immunotherapy (7.5mg/kg) once every 3 weeks (Q3W).

Radiation:
• Radiotherapy
Hypofractionated radiation technique was used to deliver a definitive radiation dose to the thoracic lesions.

Drug:
• 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.

Locations

Country	Name	City	State
China	Sun Yat-sen University	Guangzhou

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (7)

Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Car — View Citation

Bezjak A, Temin S, Franklin G, Giaccone G, Govindan R, Johnson ML, Rimner A, Schneider BJ, Strawn J, Azzoli CG. Definitive and Adjuvant Radiotherapy in Locally Advanced Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline. J Clin Oncol. 2015 Jun 20;33(18):2100-5. doi: 10.1200/JCO.2014.59.2360. Epub 2015 May 5. — View Citation

Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, Battafarano RJ, Velez MJ, Rekhtman N, Olah Z, Naidoo J, Marrone KA, Verde F, Guo H, Zhang J, Caushi JX, Chan HY, Sidhom JW, Scharpf RB, White — View Citation

Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, Ozguroglu M, Zou W, Sandler A, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, McCleland M, Mocci S, Jassem J, Spigel DR. Atezolizumab fo — View Citation

Machtay M, Bae K, Movsas B, Paulus R, Gore EM, Komaki R, Albain K, Sause WT, Curran WJ. Higher biologically effective dose of radiotherapy is associated with improved outcomes for locally advanced non-small cell lung carcinoma treated with chemoradiation: — View Citation

Provencio M, Nadal E, Insa A, Garcia-Campelo MR, Casal-Rubio J, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, De Castro Carpeno J, Cobo M, Lopez Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Pereira E, Royuela A, — View Citation

Zhang YQ, Hu PC, Wu RZ, Gu YS, Chen SG, Yu HJ, Wang XQ, Song J, Shi HC. The image quality, lesion detectability, and acquisition time of 18F-FDG total-body PET/CT in oncological patients. Eur J Nucl Med Mol Imaging. 2020 Oct;47(11):2507-2515. doi: 10.1007 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	From the start date of initial treatment to progression, death or last follow-up.	2-year
Secondary	Overall survival	From the start date of initial treatment to death or to last follow-up.	2-year
Secondary	Adverse Event	Toxicities were evaluated using the CTCAE 5.0	2-year
Secondary	Health-related Quality of Life	An individual's or perceived physical and mental health during and after treatment.	2-year
Secondary	Objective response rate	Tumor response to neoadjuvant immuno-chemotherapy and radiotherapy based on RECIST 1.1	2-year