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

NCT05978401 | Not Yet Recruiting Phase 1

• 1 other identifier: GLS-012-21
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• PFS (progression-free survival)

  24 months

• Disease Control Rate(DCR)

  24 months

Study Arms (4)

Phase I Dose-Escalation Stage：GLS-012+GLS-010

EXPERIMENTAL

Participants will be treated with escalating doses of GLS-010 + GLS-012 to determine the MTD

Drug: GLS-012+GLS-010

Phase I Expansion Stage：GLS-012+GLS-010

EXPERIMENTAL

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

GLS-012+GLS-010+pemetrexed + carboplatin

EXPERIMENTAL

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+paclitaxel+carboplatin

EXPERIMENTAL

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

Interventions

GLS-012+GLS-010 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.

Also known as: LAG3, PD-1

Phase I Dose-Escalation Stage：GLS-012+GLS-010

GLS-012+GLS-010+pemetrexed+carboplatin 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.

Also known as: LAG3, PD-1, chemotherapy

GLS-012+GLS-010+pemetrexed + carboplatin

GLS-012+GLS-010+paclitaxel+carboplatin 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.

Also known as: LAG3, PD-1, chemotherapy

GLS-012+GLS-010+paclitaxel+carboplatin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guangzhou Gloria Biosciences Co., Ltd.: lead

Study Sites (1)

Shang Hai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

MeSH Terms

Interventions

Drug Therapy

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part1 section is a dose-escalation/expansion study in a single-arm setup； Part2 section sets up a control.

Study Record Dates

• First Submitted: July 26, 2023
• First Posted: August 7, 2023
• Study Start: August 10, 2023
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2026
• Last Updated: August 7, 2023

Record last verified: 2023-08

Locations

CN (1)