Advanced Non-Small Cell Lung Cancer
Conditions
Brief summary
This is a multicenter, open Phase I/II study. The trial consists of two parts, Part1 is a dose-escalation/expansion study, Part2 is a combination of GLS-010 and GLS-010+GLS-012 with standard chemotherapy for advanced non-small-cell lung cancer respectively to assess preliminary efficacy at the combination dose.
Interventions
DRUGGLS-012+GLS-010
Two dose levels will be evaluated for GLS-012+GLS-010 administered. GLS-012+GLS-010 will be given via intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression or loss of clinical benefit.
DRUGGLS-012+GLS-010+pemetrexed+carboplatin
GLS-012+GLS-010 will be given via IV infusion on Day 1 of each 21-day cycle in combination with pemetrexed and carboplatin. Combination treatment will be administered 4\ 6 cycles.GLS-012+GLS-010/GLS-010 may continue until disease progression or loss of clinical benefit.
DRUGGLS-012+GLS-010+paclitaxel+carboplatin
GLS-012+GLS-010 will be given via IV infusion on Day 1 of each 21-day cycle in combination with paclitaxel and carboplatin. Combination treatment will be administered 4\ 6 cycles.GLS-012+GLS-010/GLS-010 may continue until disease progression or loss of clinical benefit.
Sponsors
Guangzhou Gloria Biosciences Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Part1 section is a dose-escalation/expansion study in a single-arm setup； Part2 section sets up a control； All processes do not involve blind settings.
Intervention model description
Part1 section is a dose-escalation/expansion study in a single-arm setup； Part2 section sets up a control.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects enroll in the study and sign the Informed Consent Form (ICF); 2. Aged ≥18 years and ≤75 years; 3. histologically or cytologically confirmed advanced non-small cell lung cancer without driver genes (diagnostic criteria refer to AJCC 8th edition of squamous or non-squamous non-small cell lung cancer); 4. Subjects with an Eastern Cooperative Oncology Group (ECOG) score of 0 \ 1 for physical status; 5. expected survival ≥ 12 weeks; 6. Subjects with measurable lesions (at least 1 extracranial lesion) according to the Solid Tumor Evaluation Criteria (RECIST v1.1). 7. Subjects provide formalin-fixed, paraffin-embedded tumor tissue blocks or unstained tumor specimen sections (at least 6), either archived or freshly obtained within 5 years prior to the first study treatment (freshly obtained is preferred); 8. Organ function meets the following criteria: 1. Adequate bone marrow reserve (not acceptable for corrective therapy with hematologic products or cell growth factors administered within 14 days prior to first study dose): absolute neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 90 x 109/L, and hemoglobin ≥ 9 g/dL; 2. Liver: serum albumin ≥ 3.0 g/dL; total bilirubin ≤ 1.5 times the Upper Limit of Normal (ULN), and ALT and AST ≤ 3 times the ULN (or AST and ALT ≤ 5 × ULN for patients with known liver metastases); 3. Renal: blood creatinine ≤ 1.25 times ULN; 4. Heart: left ventricular ejection fraction (LVEF) ≥ 50%. 9. Subjects of childbearing potential must be using highly effective contraception during the study and for at least 6 months after the last dose; female subjects of childbearing potential must have a negative blood pregnancy test within 3 days prior to study enrollment.
Exclusion criteria
1. Severe immunotherapy-related toxicity during prior treatment with anti-ICIs; 2. Prior grade ≥ 3 irAE on immunotherapy and who have not recovered to grade ≤ 1 from the last adverse reaction to antineoplastic therapy; 3. With primary or secondary immunodeficiency； 4. Any active, known or suspected autoimmune disease; 5. Known CNS metastases ; 6. Prior severe allergic reactions to large protein preparations/monoclonal antibodies (CTCAE V5.0 classification ≥ grade 4); 7. Previous treatment with anti-LAG-3 antibodies; 8. Other malignant tumors within 5 years prior to screening, except cured cervical carcinoma in situ and cured basal cell carcinoma of the skin; 9. Have uncontrolled cardiac clinical symptoms or disease； 10. Subjects have received a live attenuated vaccine (except inactivated viral seasonal influenza vaccine and novel coronavirus vaccine) within 4 weeks prior to the first dose and who will not receive intranasally administered live attenuated influenza vaccine; 11. Pregnant or nursing females； 12. Poorly compliant or otherwise unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT/MTD | 24 months | To evaluate GLS-012 in combination with GLS-010 dose-limiting toxicity (DLT)/maximum tolerated dose (MTD) in patients with advanced non-small cell lung cancer |
| Investigator Assessments of Overall Response Rate(ORR) | 24 months | RECIST v1.1 will be used to determine ORR by investigator |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS (progression-free survival) | 24 months | RECIST v1.1 will be used to determine PFS by investigator |
| Disease Control Rate(DCR) | 24 months | RECIST v1.1 will be used to determine DCR by investigator |
Countries
China
Outcome results
None listed