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

Phase 1

Not yet recruiting

• Conditions: Advanced Non-Small Cell Lung Cancer
• Interventions: Drug: GLS-012+GLS-010; Drug: GLS-012+GLS-010+pemetrexed+carboplatin; Drug: GLS-012+GLS-010+paclitaxel+carboplatin

• Registration Number: NCT05978401
• Lead Sponsor: Guangzhou Gloria Biosciences Co., Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-07-26
• Status Verified: 2023-08
• Study First Submitted QC: 2023-08-03
• Last Update Submitted: 2023-08-03
• Study First Posted: 2023-08-07
• Last Update Posted: 2023-08-07
• Study Start: 2023-08-10
• Primary Completion: 2025-04-01
• Study Completion: 2026-04-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 152

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Phase I Dose-Escalation Stage：GLS-012+GLS-010	GLS-012+GLS-010	Participants will be treated with escalating doses of GLS-010 + GLS-012 to determine the MTD
Phase I Expansion Stage：GLS-012+GLS-010	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.
GLS-012+GLS-010+pemetrexed + carboplatin	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.
GLS-012+GLS-010+paclitaxel+carboplatin	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Shang Hai Pulmonary Hospital; 🇨🇳 Shanghai, Shanghai, China