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

NCT05468242 | Recruiting Phase 2 DMC

• 1 other identifier: GASTO-1086
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  From the start date of initial treatment to progression, death or last follow-up.

  2-year

Secondary Outcomes (4)

• Overall survival

  2-year

• Adverse Event

  2-year

• Health-related Quality of Life

  2-year

• Objective response rate

  2-year

Study Arms (2)

Neoadjuvant Chemotherapy Plus Tislelizumab + Bevacizumab

EXPERIMENTAL

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

Drug: Neoadjuvant chemo-immunotherapy; Drug: Bevacizumab; Radiation: Radiotherapy; Drug: Tislelizumab

Neoadjuvant Chemotherapy Plus Tislelizumab

ACTIVE COMPARATOR

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

Drug: Neoadjuvant chemo-immunotherapy; Radiation: Radiotherapy; Drug: Tislelizumab

Interventions

Neoadjuvant chemo-immunotherapy DRUG

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

Neoadjuvant Chemotherapy Plus Tislelizumab; Neoadjuvant Chemotherapy Plus Tislelizumab + Bevacizumab

Bevacizumab DRUG

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

Neoadjuvant Chemotherapy Plus Tislelizumab + Bevacizumab

Radiotherapy RADIATION

Definitive radiotherapy to the thoracic lesions.

Neoadjuvant Chemotherapy Plus Tislelizumab; Neoadjuvant Chemotherapy Plus Tislelizumab + Bevacizumab

Tislelizumab 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; Neoadjuvant Chemotherapy Plus Tislelizumab + 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:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University

Guangzhou, 510060, China

RECRUITING

Related Publications (7)

• 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.

  PMID: 25944914 BACKGROUND

• 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: an analysis of the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):425-34. doi: 10.1016/j.ijrobp.2010.09.004. Epub 2010 Oct 25.

  PMID: 20980108 RESULT

• 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 Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8.

  PMID: 28885881 RESULT

• 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 J, Gabrielson E, Wang H, Rosner GL, Rusch V, Wolchok JD, Merghoub T, Taube JM, Velculescu VE, Topalian SL, Brahmer JR, Pardoll DM. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 May 24;378(21):1976-1986. doi: 10.1056/NEJMoa1716078. Epub 2018 Apr 16.

  PMID: 29658848 RESULT

• 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, Casarrubios M, Salas Anton C, Parra ER, Wistuba I, Calvo V, Laza-Briviesca R, Romero A, Massuti B, Cruz-Bermudez A. Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Nov;21(11):1413-1422. doi: 10.1016/S1470-2045(20)30453-8. Epub 2020 Sep 24.

  PMID: 32979984 RESULT

• 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 for First-Line Treatment of PD-L1-Selected Patients with NSCLC. N Engl J Med. 2020 Oct 1;383(14):1328-1339. doi: 10.1056/NEJMoa1917346.

  PMID: 32997907 RESULT

• 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/s00259-020-04823-w. Epub 2020 May 18.

  PMID: 32424483 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Bevacizumab; Radiotherapy; tislelizumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Study Officials

• Hui Liu

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bo Qiu, MD

CONTACT

+86-020-87343031; qiubo@sysucc.org.cn

DaQuan Wang, MD

CONTACT

+86-020-87343031; wangdq@sysucc.org.cn

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

Study Record Dates

• First Submitted: July 19, 2022
• First Posted: July 21, 2022
• Study Start: January 1, 2022
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: October 30, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)