safety, tolerability, and efficacy of gls-012 and gls-010 in patients with advanced non-small cell lung cancer

Conditions: Advanced Non-Small Cell Lung Cancer

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.


Eligibility criteria:
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.