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

Phase 3Not Yet RecruitingNCT05990127

Akeso642 enrolled

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%.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

642

Conditions

Locally Advanced or Metastatic NSCLC

Interventions

AK104DRUG

AK104 IV, q3w

TislelizumabDRUG

Tislelizumab IV, q3w

carboplatinDRUG

carboplatin IV, q3w

Pemetrexed

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. The subjects voluntarily participated in the study with full informed consent and signed written informed consent form. 2. Aged ≥18 years when the subject signed the informed consent. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4. Life expectancy ≥ 3 months. 5. 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). 6. No prior systemic therapy for advanced or metastatic NSCLC was received. 7. PD-L1 TPS \< 1%. 8. No EGFR sensitive mutations or ALK gene translocation alterations. Exclusion Criteria: 1. Histologically confirmed small cell lung cancer (SCLC). 2. NSCLC with driver gene mutations for approved targeted drug indications. 3. Active central nervous system (CNS) metastases were present. 4. Pulmonary radiation therapy \> 30 Gy within 6 months prior to first dose. 5. Active malignant tumors within the past 5 years, except for tumors in this study and scured local tumors. 6. Pregnant or lactating women. 7. Clinically significant cardiovascular or cerebrovascular disease. 8. 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. 9. 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. 10. Known active pulmonary tuberculosis. 11. Patients with active hepatitis B or active hepatitis C. 12. Known medical history of immunodeficiency or positive HIV test.

Locations (62)

Outcomes

Primary Outcomes

Overall Survival(OS)

OS is defined as the time from randomization to death due to any cause.

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Progression-Free Survival(PFS) by investigator(INV)

PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Secondary Outcomes

Progression-Free Survival(PFS) by Blind independent center review(BIRC)

PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Objective response rate (ORR) was assessed by INV

ORR is the proportion of subjects with CR or PR based on RECIST v1.1

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Disease control rate (DCR) was assessed by INV

Disease control rate (DCR) was assessed based on RECIST V1.1 criteria

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Time to response (TTR) was assessed by INV

The time from the first administration to the date of documented CR or PR

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Duration of response (DOR) was assessed by INV

Central Contacts

Zhifang Yao, M.D.

CONTACT

+86-0760-89873999 clinicaltrials@akesobio.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Pemetrexed IV, q3w (for Nonsquamous NSCLC)

PaclitaxelDRUG

Paclitaxel IV, q3w (for squamous NSCLC)

The first affiliated hospital of bengbu medical college

Bengbu, Anhui, China

Anhui provincial hospital

Hefei, Anhui, China

Anhui provincial cancer hospital

Hefei, Anhui, China

The first affiliated hospital of wannan medical college

Wuhu, Anhui, China

Cancer hospital, Chinese academy of medical sciences and Peking union medical college

Beijing, Beijing Municipality, China

The Fifth Medical Center of the Chinese People's Liberation Army General Hospital

Beijing, Beijing Municipality, China

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Beijing Chest hospital

Beijing, Beijing Municipality, China

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

Fujian cancer hospital

Fuzhou, Fujian, China

...and 52 more locations

Measured from the date of partial or complete response to therapy until the disease progression per RECIST v1.1 criteria

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Objective response rate (ORR) was assessed by BIRC

ORR is the proportion of subjects with CR or PR based on RECIST v1.1

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Disease control rate (DCR) was assessed BIRC

Disease control rate (DCR) was assessed based on RECIST V1.1 criteria

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Time to response (TTR) was assessed by BIRC

The time from the first administration to the date of documented CR or PR

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Duration of response (DOR) was assessed by BIRC

Measured from the date of partial or complete response to therapy until the disease progression per RECIST v1.1 criteria

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

The number of subjects experiencing adverse events (AEs)

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results.

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Pharmacokinetic

The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Antidrug antibodies (ADA) of AK104

Proportion of subjects who develop detectable anti-drug antibodies (ADAs)

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Health-related Quality of Life (HRQoL) assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)

EORTC QLQ-C30 measures cancer patients' physical, psychological, and social functions. Scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much". Higher score for the functioning scales and global health status denotes a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms.

Time frame: Through Database Cutoff Date (Up to approximately 39 months)

Health-related Quality of Life (HRQoL) assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 module (EORTC QLQ-LC29)

EORTC-QLQ-LC29 measures the quality of life in patients with lung cancer. Symptom scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much". For symptoms scales, higher scores indicated greater symptom burden.

Time frame: Through Database Cutoff Date (Up to approximately 39 months)