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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Galecto Biotech AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 May 2022 → 20 Nov 2025

Decision date (initial)

2024-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Galecto Biotech AB

External identifiers

EU CT number

2024-514419-93-00

EudraCT number

2021-003189-11

ClinicalTrials.gov

NCT05240131

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Safety, Pharmacokinetic

Part A: To assess the safety and tolerability of GB1211 200 mg and other doses established during the study, administrated BID in combination with atezolizumab.
Part B: To assess the safety and tolerability of GB1211 in the recommended dose in combination with atezolizumab compared to atezolizumab and placebo in patients with NSCLC, on a double blind, randomized fashion. To assess the efficacy of GB1211 compared to placebo by measuring the change of the longest diameters of target lesions at week 12 in NSCLC patients who are receiving atezolizumab.
Part C: To assess the long-term safety and tolerability of GB1211 in combination with atezolizumab compared to atezolizumab alone.

Secondary objectives 3

1. Part A: To determine the recommended dose of GB1211 in combination with atezolizumab for study part B.
2. Part A and B: To assess overall response rate ORR (complete response [CR] and partial response [PR]), clinical benefit rate (stable disease [SD], PR and CR), time to response (TTR), duration of response (DoR) according to RECIST v1.1 of GB1211 versus placebo in combination with atezolizumab. For part A of the study, the same parameters will be assessed for the two GB1211 dose groups. To assess the pharmacokinetics of GB1211 in combination with atezolizumab.
3. Part C: To assess ORR (CR and PR), clinical benefit (CR, PR and SD), DoR and progression-free survival (PFS). Time to PR or CR for those patients who enter the study with SD as best response.

Conditions and MedDRA coding

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).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Must be ≥ 18 years of age at the time of signing the Informed Consent Form (ICF).
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
3. 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
4. Patients must not have received immune checkpoint inhibitors previously.
5. Must be eligible for atezolizumab at 1200 mg every 3 weeks as defined in the atezolizumab product label
6. Must provide signed ICF.
7. Must have the ability to comply with the study protocol, in the investigator's judgment.
8. Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agree to refrain from donating eggs.
9. Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agree to refrain from donating sperm.
10. 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].
11. Measurable disease, as defined by RECIST v1.1.
12. 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
13. Agree to have a tumour biopsy that is eligible for Gal-3 expression evaluation before the first study drug dose.
14. Patients receiving therapeutic anticoagulation must be on stable regimen.
15. 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.

Exclusion criteria 19

1. Patients with known hypersensitivity to GB1211 or any of the excipients.
2. Life expectancy ≤ 12 weeks from the expected start of study treatment date
3. 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.
4. Patients with acute neurological events (e.g., intracranial or subarachnoid haemorrhage, stroke, intracranial trauma) within 6 months of inclusion
5. Patients with symptomatic, untreated, or actively progressing central nervous system (CNS) metastases confirmed by a CT or MRI scan.
6. 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
7. Patients with past medical history or any evidence of clinically active interstitial lung disease, including drug-induced interstitial lung disease.
8. Uncontrolled significant pleural effusion.
9. History of non-infectious pneumonitis that required steroids or current pneumonitis.
10. Patients with a history of arrhythmia, especially ventricular arrhythmias, atrial fibrillation or recent recovery of rhythm after atrial fibrillation.
11. Patients with bradycardia (<50 beats per minute).
12. Patients with left ventricular ejection fraction (LVEF) of ≤40% assessed according to local clinical practice.
13. Patients with a family history of sudden cardiac death before the age of 50.
14. Patients with a QT/QTc interval > 470 ms (for women) and > 450 ms (for men) at screening or congenital long QT syndrome.
15. Patients with history of organ transplant or hematopoietic stem cell transplantation.
16. Patients who have received GB1211 prior to this study
17. Major surgery within 3 weeks before the study
18. 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.
19. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part A: number of AEs in the 200 mg group compared to number of AEs in the dosing group (s).
2. Part B: number of AEs with GB1211 and atezolizumab compared to placebo and atezolizumab. The incidence, frequency and severity of AEs, SAEs, treatment related AEs, immune-related AEs, Grade 3 and above AEs and AEs leading to GB1211 discontinuation or study withdrawal. The incidence and frequency of laboratory parameter abnormalities.
3. Part B: The percentage change from baseline in the sum of longest diameters of target lesions at Week 12, %ΔTSWk12, based on ICR according to RECIST 1.1.
4. Part C: The number of AEs with GB1211 and atezolizumab compared to placebo and atezolizumab. The incidence, frequency and severity of AEs, SAEs, treatment related AEs, immune-related AEs, Grade 3 and above AEs and AEs leading to GB1211 discontinuation or study withdrawal.

Secondary endpoints 4

1. Part A: The recommended tolerable dose of GB1211 in combination with atezolizumab determined by assessment of SAEs, treatment related AEs, immune-related AEs, Grade 3 and above AEs and AEs leading to GB1211 discontinuation or study withdrawal in the sentinel groups.
2. Part A and B: Clinical effects in accordance with RECIST v1.1: o ORR based on Local Tumour Assessment (LTA) (Part A) and ICR (Part B). o DoR and TTR. o TTP is defined as the time from randomisation until objective tumour progression. TTP does not include deaths. o Disease Control defined as patients with a response or stable disease, assessed at each imaging assessment from randomisation to progression or death due to any cause, whichever occurs first.
3. Part A and B: Plasma concentrations of GB1211 and derived pharmacokinetic parameters including Cmax, Tmax, AUC and others, as appropriate.
4. Part C: ORR (CR and PR), clinical benefit (CR, PR and SD), DoR and PFS. Time to PR or CR for those patients who enter the study with SD as best response. PFS is defined as the time from the first dose until the first documentation of disease progression or death due to any cause, whichever occurs first.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Galecto Biotech AB

Sponsor organisation

Galecto Biotech AB

Address

Ole Maaloees Vej 3

City

Copenhagen N

Postcode

2200

Country

Denmark

Scientific contact point

Organisation

Galecto Biotech AB

Contact name

Hans Schambye

Public contact point

Organisation

Galecto Biotech AB

Contact name

Chief Medical Officer

Third parties 8

Locations

2 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications