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

NCT ID: NCT05978401

Last Updated: 2023-08-07

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 152 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-10
• Study Completion Date: 2026-04-01

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.

Conditions

Advanced Non-Small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

GLS-012+GLS-010

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

GLS-012+GLS-010

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

GLS-012+GLS-010+pemetrexed+carboplatin

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

GLS-012+GLS-010+paclitaxel+carboplatin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

LAG3; PD-1; LAG3; PD-1; LAG3; PD-1; chemotherapy; LAG3; PD-1; chemotherapy

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangzhou Gloria Biosciences Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Shang Hai Pulmonary Hospital

Shanghai, Shanghai Municipality, China

Countries

China

Facility Contacts

Caicun Zhou

Role: primary

caicunzhoudr@163.com

021-65115006

Other Identifiers

GLS-012-21

Identifier Type: -

Identifier Source: org_study_id