Safety, Tolerability, and Efficacy of GLS-012 and GLS-010 in Patients With Advanced Non-Small Cell Lung Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase I Dose-Escalation Stage：GLS-012+GLS-010 Participants will be treated with escalating doses of GLS-010 + GLS-012 to determine the MTD |
Drug: GLS-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.
Other Names:
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| Experimental: Phase I Expansion Stage：GLS-012+GLS-010 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
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.
Other Names:
|
| Experimental: GLS-012+GLS-010+pemetrexed + carboplatin 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
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.
Other Names:
|
| Experimental: GLS-012+GLS-010+paclitaxel+carboplatin 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
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subjects enroll in the study and sign the Informed Consent Form (ICF);
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Aged ≥18 years and ≤75 years;
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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);
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Subjects with an Eastern Cooperative Oncology Group (ECOG) score of 0 ~1 for physical status;
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expected survival ≥ 12 weeks;
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Subjects with measurable lesions (at least 1 extracranial lesion) according to the Solid Tumor Evaluation Criteria (RECIST v1.1).
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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);
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Organ function meets the following criteria:
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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;
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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);
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Renal: blood creatinine ≤ 1.25 times ULN;
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Heart: left ventricular ejection fraction (LVEF) ≥ 50%.
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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:
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Severe immunotherapy-related toxicity during prior treatment with anti-ICIs;
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Prior grade ≥ 3 irAE on immunotherapy and who have not recovered to grade ≤ 1 from the last adverse reaction to antineoplastic therapy;
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With primary or secondary immunodeficiency；
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Any active, known or suspected autoimmune disease;
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Known CNS metastases ;
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Prior severe allergic reactions to large protein preparations/monoclonal antibodies (CTCAE V5.0 classification ≥ grade 4);
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Previous treatment with anti-LAG-3 antibodies;
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Other malignant tumors within 5 years prior to screening, except cured cervical carcinoma in situ and cured basal cell carcinoma of the skin;
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Have uncontrolled cardiac clinical symptoms or disease；
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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;
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Pregnant or nursing females；
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Poorly compliant or otherwise unsuitable for participation in this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Shang Hai Pulmonary Hospital | Shanghai | Shanghai | China | 200433 |
Sponsors and Collaborators
- Guangzhou Gloria Biosciences Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GLS-012-21