A Study of AK104/Tislelizumab With Chemotherapy as First-line Treatment in PD-L1 TPS < 1% Non-small Cell Lung Cancer

Official title

A Randomized, Double-blind, Phase III Trial to Compare the Efficacy and Safety of AK104 Combined With Chemotherapy to Tislelizumab Combined With Chemotherapy as First-line Treatment in PD-L1 TPS < 1% Non-small Cell Lung Cancer (NSCLC)

Overview

This is a randomized, double-blind, phase III clinical study to compare the efficacy and safety of AK104 combined chemotherapy versus Tislelizumab combined chemotherapy in first-line treatment of Locally advanced or metastatic NSCLC with PD-L1 TPS \< 1%.

Interventions

• Drug AK104
  AK104 IV, q3w
• Drug Tislelizumab
  Tislelizumab IV, q3w
• Drug carboplatin
  carboplatin IV, q3w
• Drug Pemetrexed
  Pemetrexed IV, q3w (for Nonsquamous NSCLC)
• Drug Paclitaxel
  Paclitaxel IV, q3w (for squamous NSCLC)

Primary outcome measures

• Overall Survival(OS) [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]
• Progression-Free Survival(PFS) by investigator(INV) [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]

Secondary outcome measures (12)

• Progression-Free Survival(PFS) by Blind independent center review(BIRC) [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]
• Objective response rate (ORR) was assessed by INV [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]
• Disease control rate (DCR) was assessed by INV [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]
• Time to response (TTR) was assessed by INV [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]
• Duration of response (DOR) was assessed by INV [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]
• Objective response rate (ORR) was assessed by BIRC [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]
• Disease control rate (DCR) was assessed BIRC [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]
• Time to response (TTR) was assessed by BIRC [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]
• Duration of response (DOR) was assessed by BIRC [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]
• The number of subjects experiencing adverse events (AEs) [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]
• Pharmacokinetic [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]
• Antidrug antibodies (ADA) of AK104 [Time frame: Through Database Cutoff Date (Up to approximately 39 months)]

Eligibility criteria

Inclusion criteria

• The subjects voluntarily participated in the study with full informed consent and signed written informed consent form.
• Aged ≥18 years when the subject signed the informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 3 months.
• Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) that not amenable to complete surgical resection and not amenable to radical concurrent/sequential chemoradiation or metastatic (Stage IV) NSCLC (American Joint Committee on Cancer \[AJCC\] 8th edition).
• No prior systemic therapy for advanced or metastatic NSCLC was received.
• PD-L1 TPS < 1%.
• No EGFR sensitive mutations or ALK gene translocation alterations.

Exclusion criteria

• Histologically confirmed small cell lung cancer (SCLC).
• NSCLC with driver gene mutations for approved targeted drug indications.
• Active central nervous system (CNS) metastases were present.
• Pulmonary radiation therapy > 30 Gy within 6 months prior to first dose.
• Active malignant tumors within the past 5 years, except for tumors in this study and scured local tumors.
• Pregnant or lactating women.
• Clinically significant cardiovascular or cerebrovascular disease.
• Subjects with a known history of severe hypersensitivity to other monoclonal antibodies. A known history of allergy or hypersensitivity to all investigational drugs or any of their components.
• Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment, or autoimmune diseases that may relapse or require scheduled treatment as judged by the Investigator.
• Known active pulmonary tuberculosis.
• Patients with active hepatitis B or active hepatitis C.
• Known medical history of immunodeficiency or positive HIV test.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 62 centers

• The first affiliated hospital of bengbu medical college — Bengbu
• Anhui provincial hospital — Hefei
• Anhui provincial cancer hospital — Hefei
• The first affiliated hospital of wannan medical college — Wuhu
• Cancer hospital, Chinese academy of medical sciences and Peking union medical college — Beijing
• The Fifth Medical Center of the Chinese People's Liberation Army General Hospital — Beijing
• Beijing Cancer Hospital — Beijing
• Beijing Chest hospital — Beijing
• … and 54 more centers

Identifiers

NCT: NCT05990127 · AK104-307

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗