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)
Overview
- Phase
- Phase 1
- Intervention
- GLS-012+GLS-010
- Conditions
- Advanced Non-Small Cell Lung Cancer
- Sponsor
- Guangzhou Gloria Biosciences Co., Ltd.
- Enrollment
- 152
- Locations
- 1
- Primary Endpoint
- DLT/MTD
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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);
Exclusion Criteria
- •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;
Arms & Interventions
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
Intervention: GLS-012+GLS-010
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.
Intervention: GLS-012+GLS-010
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.
Intervention: GLS-012+GLS-010+pemetrexed+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.
Intervention: GLS-012+GLS-010+paclitaxel+carboplatin
Outcomes
Primary Outcomes
DLT/MTD
Time Frame: 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)
Time Frame: 24 months
RECIST v1.1 will be used to determine ORR by investigator
Secondary Outcomes
- PFS (progression-free survival)(24 months)
- Disease Control Rate(DCR)(24 months)