This study is an open label study followed by a randomised, double-blind, placebo-controlled, parallel group and an extension 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).
The study will be carried out in three parts: The core study is comprised of part A (dose finding and safety) and part B (efficacy and safety). Part C is an extension phase of the core study to collect long-term safety data. In part A of the study, open-label sentinel dosing will be undertaken to assess safety and tolerability of GB1211 at 200 mg BID and 100 mg BID in combination with atezolizumab including 4 patients in each dose cohort. Patients enrolled in part A may continue treatment with 200 mg GB1211 BID or 100 mg GB1211 BID and atezolizumab for 12 weeks, after which the patients will be offered treatment in the part C study, if they have achieved clinical benefit as best response during the first 12 weeks of treatment (SD or better response according to RECIST 1.1). In part B of the study, patients will randomised (1:1) for blinded treatment to receive either GB1211 (200 or 100 mg BID to be selected from part A) or placebo, in addition to atezolizumab, for 12 weeks, after which the patients will be offered treatment in part C, if they have achieved clinical benefit as best response during the first 12 weeks of treatment (SD or better response according to RECIST 1.1). In part C, this treatment will be blinded until part B has been unblinded. After unblinding, patients will continue to receive the same treatment they had received in part B: GB1211 and atezolizumab or atezolizumab only (no placebo) if they experience continued benefit from treatment. The patients will be treated until disease progression or unacceptable toxicity. After the end of the study treatment all patients will be followed 4 weeks for safety, regardless of the study part in which the last study treatment was given.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
88
GB1211 is a galectin 3 inhibitor an orally available small molecular anti-fibrotic. It is administered orally twice a day.
Placebo is administered orally twice a day.
Atezolizumab is an PD-L1 inhibitor administered as an intravenous infusion every three weeks at a dose of 1200mg
Centre Georges Grancois Leclerc
Dijon, France
CHRU
Tours, France
Samodzielny Publiczny Zespol Gruzlicy I Chorob Pluc
Olsztyn, Poland
Hospital Universitario y Politécnico La Fe
Valencia, València, Spain
PART A - To assess the safety and tolerability of GB1211 in combination with atezolizumab.
Incidence and severity of adverse events as reported by investigators.
Time frame: 3 weeks
PART B - To assess the safety and tolerability of GB1211 in combination with atezolizumab compared to atezolizumab and placebo
Incidence and severity of adverse events
Time frame: 12 weeks
Part B -To assess the efficacy of GB1211 compared to placebo by measuring the change of the longest diameters of target lesions at week 12.
Independent central review of CT, PET/CT or MRI scan according to RECIST 1.1
Time frame: 12 weeks
Part C - To assess the long-term safety and tolerability of GB1211 in combination with atezolizumab compared to atezolizumab alone.
Incidence and severity of adverse events.
Time frame: 12 - 40 weeks
Part A -To determine the recommended dose (200 mg BID or 100 mg BID) of GB1211 in combination with atezolizumab.
Incidence and severity of adverse events as reported by investigators.
Time frame: 3 weeks
Part A and B - To assess response rate according to RECIST v1.1 of GB1211 versus placebo in combination with atezolizumab.
Independent central review of CT, PET/CT or MRI scan according to RECIST 1.1
Time frame: 12 weeks
To measure the maximum plasma concentration of GB1211 (Cmax)
Plasma concentrations of GB1211 \[Time Frame: Part A - Cycle 1 Day 1: pre-dose, 2, 4, 6, 8, 12 hours post-dose; Cycle 2 Day 1: pre-dose, 2, 4, 6, 8, 12 hours post-dose; Cycle 3 Day 1: pre-dose, between 2 and 4 hours post-dose, between 4 and 8 hours post-dose; End of Treatment: pre-dose, between 2 and 4 hours post-dose, between 4 and 8 hours post-dose. Part B - Cycle 1 Day 1: pre-dose, between 2 and 4 hours post-dose, between 4 and 8 hours post-dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose; End of Treatment: pre-dose, between 2 and 4 hours post-dose, between 4 and 8 hours post-dose\] for the calculation of pharmacokinetic parameter maximum plasma concentration (Cmax) of GB1211
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Hospital Universitari Vall d'Hebron
Barcelona, Spain
Time frame: 12 weeks
To measure the time of maximum plasma concentration of GB1211 (Tmax)
Plasma concentrations of GB1211 \[Time Frame: Part A - Cycle 1 Day 1: pre-dose, 2, 4, 6, 8, 12 hours post-dose; Cycle 2 Day 1: pre-dose, 2, 4, 6, 8, 12 hours post-dose; Cycle 3 Day 1: pre-dose, between 2 and 4 hours post-dose, between 4 and 8 hours post-dose; End of Treatment: pre-dose, between 2 and 4 hours post-dose, between 4 and 8 hours post-dose. Part B - Cycle 1 Day 1: pre-dose, between 2 and 4 hours post-dose, between 4 and 8 hours post-dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose; End of Treatment: pre-dose, between 2 and 4 hours post-dose, between 4 and 8 hours post-dose\] for the calculation of pharmacokinetic parameter time of the maximum plasma concentration (Tmax) of GB1211
Time frame: 12 weeks
To measure the area under the concentration-time curve of GB1211 (AUC)
Plasma concentrations of GB1211 \[Time Frame: Part A - Cycle 1 Day 1: pre-dose, 2, 4, 6, 8, 12 hours post-dose; Cycle 2 Day 1: pre-dose, 2, 4, 6, 8, 12 hours post-dose; Cycle 3 Day 1: pre-dose, between 2 and 4 hours post-dose, between 4 and 8 hours post-dose; End of Treatment: pre-dose, between 2 and 4 hours post-dose, between 4 and 8 hours post-dose. Part B - Cycle 1 Day 1: pre-dose, between 2 and 4 hours post-dose, between 4 and 8 hours post-dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose; End of Treatment: pre-dose, between 2 and 4 hours post-dose, between 4 and 8 hours post-dose\] for the calculation of pharmacokinetic parameter area under the plasma concentration versus time curve (AUC) of GB1211
Time frame: 12 weeks
Part C - To assess response rates for those patients who enter the study with at least Stable Disease as best response.
Independent central review of CT, PET/CT or MRI scan according to RECIST 1.1
Time frame: 12 - 40 weeks