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

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: GLS-012+GLS-010; Drug: GLS-012+GLS-010; Drug: GLS-012+GLS-010+pemetrexed+carboplatin; Drug: GLS-012+GLS-010+paclitaxel+carboplatin

• Study Type: Interventional
• Enrollment (Estimated): 152
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Shang Hai Pulmonary Hospital
      • Contact: Caicun Zhou; Phone Number: 021-65115006; Email: caicunzhoudr@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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: PD-1; LAG3; 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: PD-1; LAG3
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; 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: PD-1; LAG3; 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: PD-1; LAG3
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: chemotherapy; PD-1; LAG3
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: chemotherapy; PD-1; LAG3

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Guangzhou Gloria Biosciences Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): August 10, 2023
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: July 26, 2023
• First Submitted That Met QC Criteria: August 3, 2023
• First Posted (Actual): August 7, 2023

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Folic Acid Antagonists; Carboplatin; Paclitaxel; Pemetrexed
• Other Study ID Numbers: GLS-012-21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No