A Study to Investigate the Safety and Efficacy of GB1211 (a Galectin-3 Inhibitor) in Combination With Atezolizumab in Patients With Non-Small Cell Lung Cancer (NSCLC).

This is an interventional treatment trial for Non-Small Cell Lung Cancer Read More

Inclusion criteria:

Patients must meet the following criteria for study entry:

1. Must be ≥ 18 years of age at the time of signing the Informed Consent Form (ICF).
2. Must provide signed ICF.
3. Must have the ability to comply with the study protocol, in the investigator's judgment.
4. Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agree to refrain from donating eggs.
5. Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agree to refrain from donating sperm.
6. Diagnosed NSCLC with adenocarcinoma and its variants according to the 2015 WHO classification (Travis et al. 2015).
7. Measurable disease, as defined by RECIST v1.1.

8. Have histologically or cytologically confirmed advanced or metastatic NSCLC defined as:

   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].

9. Expressing PD-L1 on at least 50% of tumour cells, as determined through use of the Dako PD-L1 IHC 22C3 pharmDx assay or the Ventana PD-L1 IHC SP263 assay.
10. Agree to have a tumour biopsy that is eligible for Gal-3 expression evaluation before the first study drug dose.
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
12. 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.
13. Patients must not have received immune checkpoint inhibitors (ICI) previously.
14. Must be eligible for atezolizumab at 1200 mg every 3 weeks as defined in the atezolizumab product label.
15. Patients receiving therapeutic anticoagulation must be on stable regimen.

16. 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 x 109/L (1500/µL) without granulocyte colony-stimulating factor support.
    • Lymphocyte count ≥0.5 x 109/L (500/µL).
    • Platelet count ≥ 100 x 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 x upper limit of normal (ULN), with the following exceptions:

      • Patients with documented liver metastases: AST and ALT ≤ 5 x ULN.
      • Patients with documented liver or bone metastases: ALP ≤ 5 x ULN.
    • Total bilirubin ≤ 1.5 x ULN with the following exception:

Patients with known Gilbert disease: total bilirubin ≤ 3 x ULN.

• Creatinine clearance ≥50 mL/min (calculated using the Cockcroft-Gault formula).
• Albumin ≥25 g/L (2.5 g/dL).
• For patients not receiving therapeutic anticoagulation: INR and a PTT ≤1.5 x ULN.

Exclusion criteria:

Patients who meet any of the following criteria will be excluded from study participation.

1. Known contraindications for treatment with PD-1/PD-L1 inhibitors.
2. Patients with known hypersensitivity to GB1211 or any of the excipients.
3. Women who are pregnant or breast-feeding or intending to become pregnant during study treatment or within 9 months after the final dose of study treatment.
4. Women of childbearing potential without a negative serum pregnancy test result within 14 days prior to initiation of study treatment.
5. Women of child-bearing potential or men who are unwilling to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures during the study, and do not agree to refrain from donating sperm or egg cells from the first dose of study drug up to 9 months after the last dose of study drug.
6. Patients with adenosquamous carcinomas, defined as tumours composed of more than 10 percent malignant glandular and squamous components.
7. Presence of oncogenes EGFR (exon 19 deletions, pL858R point mutation in exon 21), ALK rearrangements, RET rearrangements, or ROS1 mutation.
8. Hepatic impairment of Child Pugh B or C.
9. Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test result at screening) and/or hepatitis C virus (HCV).
10. Patients with active human immunodeficiency virus (HIV).
11. Patients who are positive for coronavirus disease 2019 (COVID-19) by naso-pharyngeal swab test.
12. Active or history of autoimmune disease or immune deficiency.
13. Patients with severe infection within 4 weeks prior to initiation of study treatment.
14. Patients with acute neurological events (e.g., intracranial or subarachnoid haemorrhage, stroke, intracranial trauma) within 6 months of inclusion.
15. Patients with symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
16. No tumour specimen, obtained in the last 6 months, is available to analyse galectin expression and it is not feasible to obtain a new specimen (note: cytology samples are admissible).
17. Patients with past medical history or any evidence of clinically active interstitial lung disease.
18. Uncontrolled significant pleural effusion.
19. History of non-infectious pneumonitis that required steroids or current pneumonitis.
20. Patients with significant cardiovascular disease such as but not limited to unstable arrhythmia requiring treatment, myocardial infarction, ischaemia, transient ischemic attack (TIA), congestive heart failure New York Heart Association (NYHA) class II-IV, left ventricular hypertrophy, cardiomyopathy, conduction disorder, uncontrolled hypertension, bradycardia, LVEF< 40% or a QT/QTc interval > 470 ms.