Safety, Tolerability, and Efficacy of GLS-012 and GLS-010 in Patients With Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I/II Study Evaluating the Safety, Tolerability, and Efficacy of GLS-012 and GLS-010 in Patients With Advanced Non-Small Cell Lung Cancer (Triumph-02)

Conditions
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Advanced Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: GLS-012+GLS-010
* Drug: GLS-012+GLS-010
* Drug: GLS-012+GLS-010+pemetrexed+carboplatin
* Drug: GLS-012+GLS-010+paclitaxel+carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects enroll in the study and sign the Informed Consent Form (ICF); Aged ≥18 years and ≤75 years; 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); Subjects with an Eastern Cooperative Oncology Group (ECOG) score of 0  1 for physical status; expected survival ≥ 12 weeks; Subjects with measurable lesions (at least 1 extracranial lesion) according to the Solid Tumor Evaluation Criteria (RECIST v1.1). 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); Organ function meets the following criteria: 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; 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); Renal: blood creatinine ≤ 1.25 times ULN; Heart: left ventricular ejection fraction (LVEF) ≥ 50%. 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: Severe immunotherapy-related toxicity during prior treatment with anti-ICIs; Prior grade ≥ 3 irAE on immunotherapy and who have not recovered to grade ≤ 1 from the last adverse reaction to antineoplastic therapy; With primary or secondary immunodeficiency； Any active, known or suspected autoimmune disease; Known CNS metastases ; Prior severe allergic reactions to large protein preparations/monoclonal antibodies (CTCAE V5.0 classification ≥ grade 4); Previous treatment with anti-LAG-3 antibodies; Other malignant tumors within 5 years prior to screening, except cured cervical carcinoma in situ and cured basal cell carcinoma of the skin; Have uncontrolled cardiac clinical symptoms or disease； 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; Pregnant or nursing females； Poorly compliant or otherwise unsuitable for participation in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Part1 section is a dose-escalation/expansion study in a single-arm setup； Part2 section sets up a control.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I Dose-Escalation Stage：GLS-012+GLS-010<br>Participants will be treated with escalating doses of GLS-010 + GLS-012 to determine the MTD | Drug: GLS-012+GLS-010<br>* 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.<br>* Other names: PD-1;|
| Experimental: Phase I Expansion Stage：GLS-012+GLS-010<br>Participants will be enrolled in the expansion stage to better characterize the safety, tolerability, PK variability, and preliminary efficacy of GLS-012+GLS-010 in Advanced Non-Small Cell Lung Cancer. | Drug: GLS-012+GLS-010<br>* Target 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.<br>* Other names: PD-1;|
| Experimental: GLS-012+GLS-010+pemetrexed + carboplatin<br>Participants will be enrolled in the expansion stage to better characterize the safety, PK variability, and preliminary efficacy of GLS-012+GLS-010+pemetrexed+carboplatin in Advanced Non-Small Cell Lung Cancer. | Drug: GLS-012+GLS-010+pemetrexed+carboplatin<br>* 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.<br>* Other names: chemotherapy;|
| Experimental: GLS-012+GLS-010+paclitaxel+carboplatin<br>Participants will be enrolled in the expansion stage to better characterize the safety, PK variability, and preliminary efficacy of GLS-012+GLS-010+paclitaxel+carboplatin in Advanced Non-Small Cell Lung Cancer. | Drug: GLS-012+GLS-010+paclitaxel+carboplatin<br>* 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.<br>* Other names: chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT/MTD | 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 | 24 months | 
| Investigator Assessments of Overall Response Rate(ORR) | RECIST v1.1 will be used to determine ORR by investigator | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS (progression-free survival) | RECIST v1.1 will be used to determine PFS by investigator | 24 months | 
| Disease Control Rate(DCR) | RECIST v1.1 will be used to determine DCR by investigator | 24 months |