A clinical study to test the safety and efficacy of GB1211 in combination with atezolizumab in patients with Non-Small Cell Lung Cancer (NSCLC).

Prior treatment

• Patients who have received GB1211 prior to this study
• Major surgery within 3 weeks before the study
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment.
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour necrosis factor-a [TNF-a] agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment.

Other illness

• Patients with known hypersensitivity to GB1211 or any of the excipients.
• Patients with a history of arrhythmia, especially ventricular arrhythmias, atrial fibrillation or recent recovery of rhythm after atrial fibrillation.
• Patients with history of organ transplant or hematopoietic stem cell transplantation.
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis.
• Patients with acute neurological events (e.g., intracranial or subarachnoid haemorrhage, stroke, intracranial trauma) within 6 months of inclusion
• History of malignancy other than NSCLC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate ≥ 90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
• Patients with past medical history or any evidence of clinically active interstitial lung disease, including drug-induced interstitial lung disease.
• History of non-infectious pneumonitis that required steroids or current pneumonitis.

Lab values

• Patients with left ventricular ejection fraction (LVEF) of ≤40% assessed according to local clinical practice.
• Patients with a QT/QTc interval > 470 ms (for women) and > 450 ms (for men) at screening or congenital long QT syndrome.

Age

• Patients with a family history of sudden cardiac death before the age of 50.

Other

• Patients with bradycardia (<50 beats per minute).
• Life expectancy ≤ 12 weeks from the expected start of study treatment date
• Patients with symptomatic, untreated, or actively progressing central nervous system (CNS) metastases confirmed by a CT or MRI scan.
• Uncontrolled significant pleural effusion.

• Must be ≥ 18 years of age at the time of signing the Informed Consent Form (ICF).
• Diagnosed NSCLC stage IIIB that either progressed after curative therapy (chemoradiation and/or surgery) or is not candidate to curative therapy, or Stage IV metastatic disease (de novo or distant relapse) [According to UICC TNM edition 8].
• Measurable disease, as defined by RECIST v1.1.
• Expressing PD-L1 on at least 50% of tumour cells (PD-L1 stained ≥ 50% of tumour cells [TC ≥ 50%] or PD-L1 stained tumour-infiltrating immune cells [IC] covering ≥ 10% of the tumour area [IC ≥ 10%]), as determined through use of the Dako PD-L1 IHC 22C3 pharmDx assay or the Ventana PD-L1 IHC SP263 assay
• Agree to have a tumour biopsy that is eligible for Gal-3 expression evaluation before the first study drug dose.
• Patients receiving therapeutic anticoagulation must be on stable regimen.
• Adequate haematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment: • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/μL) without granulocyte colony-stimulating factor support. • Lymphocyte count ≥ 0.5 × 109/L (500/μL). • Platelet count ≥ 100 × 109/L (100,000/μL) without transfusion. • Haemoglobin ≥ 90 g/L (9 g/dL). Patients may be transfused to meet this criterion. • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × upper limit of normal (ULN), with the following exceptions: o Patients with documented liver metastases: AST and ALT ≤ 5 × ULN. o Patients with documented liver or bone metastases: ALP ≤ 5 × ULN. • Total bilirubin ≤ 1.5 × ULN with the following exception: Patients with known Gilbert disease: total bilirubin ≤ 3 × ULN. • Creatinine clearance ≥ 50 mL/min (calculated using the CockcroftGault formula). • Albumin ≥ 25 g/L (2.5 g/dL). • For patients not receiving therapeutic anticoagulation: INR and a PTT ≤ 1.5 × ULN.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have not received prior systemic chemotherapy for the treatment of recurrent, advanced or metastatic disease, treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 4 weeks prior to diagnosis of recurrent advanced or metastatic disease
• Patients must not have received immune checkpoint inhibitors previously.
• Must be eligible for atezolizumab at 1200 mg every 3 weeks as defined in the atezolizumab product label
• Must provide signed ICF.
• Must have the ability to comply with the study protocol, in the investigator's judgment.
• Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agree to refrain from donating eggs.
• Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agree to refrain from donating sperm.