A Phase 3, Randomized, Double-Blind Study of BGB A1217, an Anti TIGIT Antibody, in Combination With Tislelizumab Compared to Pembrolizumab in Patients With Previously Untreated, PD L1 Selected, and Locally Advanced, Unresectable, or Metastatic Non Small Cell Lung Cancer

Phase 1

• Conditions: MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]; Previously Untreated, PD-L1-Selected, and Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer

• Registration Number: EUCTR2020-004985-21-IT
• Lead Sponsor: BeiGene Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-10-05
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 605

Inclusion Criteria

1.Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of
assessments.
2.Age = 18 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking
place).
3.Histologically or cytologically documented locally advanced or recurrent NSCLC that is not eligible for curative surgery and/or definitive
radiotherapy with or without chemoradiotherapy, or metastatic nonsquamous or squamous NSCLC.
4.No prior systemic treatment for metastatic NSCLC.
5.Agreement to provide archival tissue (formalin-fixed paraffinembedded block containing tumor [preferred] or 6 to 15 freshly cut unstained slides) or fresh biopsy (if archival tissue is not available) for prospective central evaluation of PD-L1 levels and retrospective analysis
of other biomarkers.
6.Tumors with PD-L1 TC = 50% expression as centrally determined.
7.At least 1 measurable lesion as defined per RECIST v1.1.
8.ECOG Performance Status = 1.
9.Adequate organ function as indicated by the following laboratory values during screening:
a.Patients must not have required blood transfusion or growth factor support = 14 days before sample collection at screening for the
following:
-Absolute neutrophil count (ANC) = 1.5 x 109/L
-Platelets = 75 x 109/L or 100 x 109/L in chemotherapy combination studies
-Hemoglobin = 90 g/L
b.Serum creatinine = 1.5 x upper limit of normal (ULN) or estimated Glomerular Filtration Rate = 60 mL/min/1.73 m2 by Chronic Kidney
Disease Epidemiology Collaboration equation (Appendix 8).
c.Serum total bilirubin = 1.5 x ULN (total bilirubin must be < 3 x ULN for patients with Gilberts syndrome).
d.AST and ALT = 2.5 x ULN or < 5 x ULN if hepatic metastases present.
10.Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and for =
120 days after the last dose of study drug, and must have a negative urine or serum pregnancy test = 7 days before randomization.
11.Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study and for = 120 days after the
last dose of study drug.
•A sterile male is defined as one for whom azoospermia has been previously demonstrated in a semen sample examination as definitive
evidence of infertility.
•Males with known low sperm counts (consistent with subfertility) are not to be considered sterile for purposes of this study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 450
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 155

Exclusion Criteria

1.Known sensitizing mutation in the EGFR gene or an ALK fusion oncogene.
Note: Patients with nonsquamous NSCLC whose EGFR mutational status is unknown will be required to have a tissue-based EGFR test either locally or centrally at prescreening. Patients found to have EGFRsensitizing mutations will be excluded.
2.Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-TIGIT, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways.3.Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
•Patients with a history of treated and, at the time of screening, stable central nervous system (CNS) metastases are eligible, provided they
meet all the following:
-Brain imaging at screening shows no evidence of interim progression, patient is clinically stable for at least 2 weeks and without evidence of new brain metastases.
-Measurable and/or evaluable disease outside the CNS.
-No ongoing requirement for corticosteroids as therapy for CNS disease; off steroids 3 days before randomization; anticonvulsants at a stable dose are allowed.
-No stereotactic radiation or whole-brain radiation within 14 days before randomization.
4.Active autoimmune diseases or history of autoimmune diseases that may relapse.
5.Any active malignancy = 2 years before randomization except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast).
6.Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other
immunosuppressive medication = 14 days before randomization.
b.Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption.c.Short course (= 7 days) of
corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type
hypersensitivity reaction caused by contact allergen.
7.Uncontrolled diabetes or > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical
management or = Grade 3 hypoalbuminemia = 14 days before randomization.
8.Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within 2 weeks of intervention).
Patients with symptomatic pleural effusion are excluded unless the patient undergoes a therapeutic thoracentesis or has had pleurodesis
(more than 2 weeks prior) and has subsequently stable effusions.
9.History of interstitial lung disease, noninfectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases, etc. Patients with significantly impaired pulmonary function, or who require supplemental oxygen at baseline must undergo an
assessment of pulmonary function at screening
10.Infection (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days before
randomization.
11.Untreated chronic hepatitis B or chronic HBV carriers with HBV DNA > 500 IU/mL (or>2500 copies/mL) at screening.
12.Patients with active hepatitis C.
13.Known history of HIV infection.
14.Any major surgical procedure = 28 days before randomization. Patients must have recovered adequately from the toxicity and/or
complications from the intervention before randomiza

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified