A Study of SKB264 in Combination with Pembrolizumab Versus Chemotherapy in Combination with Pembrolizumab As First-Line Treatment for PD-L1 Negative Patients with Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer

Phase 3

Recruiting

Interventions: Drug: SKB264
Drug: pemetrexed
Drug: Pembrolizumab
Drug: carboplatin or cisplatin

Brief Summary: The study aims to evaluate the efficacy and safety of SKB264 in combination with pembrolizumab versus chemotherapy in combination with pembrolizumab in the first-line treatment of patients with locally advanced or metastatic non-squamous NSCLC with PD-L1 negative.

Detailed Description: This is a randomized, open-label, multicenter, Phase 3 study to evaluate the efficacy and safety of SKB264 in combination with pembrolizumab versus chemotherapy in combination with pembrolizumab in the first-line treatment of patients with locally advanced or metastatic non-squamous NSCLC with PD-L1 negative.

Recruitment & Eligibility

Inclusion Criteria

Histologically or cytologically confirmed non-squamous NSCLC, and unsuitable for radical surgery and/or radical concurrent/sequential radiochemotherapy, locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) NSCLC;
EGFR-sensitive mutation negative [no exon 19 deletion (19-Del) or exon 21 point mutation (L858R mutation)] and ALK fusion gene negative, without known ROS1 gene fusion, NTRK gene fusion, BRAF V600E mutation, etc. that have been approved for targeted therapy driving gene alterations;
No prior systemic anti-cancer therapy for locally advanced or metastatic NSCLC;
Participants whose tumours are PD-L1 TPS ≥ 1%;
At least one measurable lesion per RECIST v1.1;
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 with no worsening within 7 days prior to randomization;
A life expectancy of at least 12 weeks;
Adequate organ and bone marrow function;

Exclusion Criteria

Histologically or cytologically confirmed tumors with a component of small cell lung cancer, neuroendocrine carcinoma, sarcomatoid carcinoma, or squamous cell carcinoma exceeding 10%;
Previously received immune checkpoint inhibitors,checkpoint agonists or any treatment targeting the immune mechanism of tumors such as immune cell therapy;
Active second malignancy;
Symptomatic or uncontrolled cardiovascular disease，serious thromboembolic；
History of noninfectious pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD;
Active infection requiring systemic therapy within 2 weeks of randomization;
Active hepatitis B or hepatitis C virus infection;
Human immunodeficiency virus (HIV) positive or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection;
Major surgery within 4 weeks prior to randomization or expected major surgery during the study;
Pregnant or lactating women;

Arm && Interventions

Group	Intervention	Description
Pembrolizumab+Chemotherapy	carboplatin or cisplatin	Participants will receive Pembrolizumab on Day1 of each 6-week cycle,Chemotherapy on Day1 and Day 22 of each 6-week
Pembrolizumab+Chemotherapy	pemetrexed	Participants will receive Pembrolizumab on Day1 of each 6-week cycle,Chemotherapy on Day1 and Day 22 of each 6-week
SKB264+Pembrolizumab	SKB264	Participants will receive SKB264 on Day 1、Day 15 and Day 29 of each 6-week cycle,Pembrolizumab on Day1 of each 6-week cycle.
SKB264+Pembrolizumab	Pembrolizumab	Participants will receive SKB264 on Day 1、Day 15 and Day 29 of each 6-week cycle,Pembrolizumab on Day1 of each 6-week cycle.
Pembrolizumab+Chemotherapy	Pembrolizumab	Participants will receive Pembrolizumab on Day1 of each 6-week cycle,Chemotherapy on Day1 and Day 22 of each 6-week

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) assessed by Blinded Independent Central Review (BICR)	Randomization up to approximately 28 months	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Randomization up to approximately 43 months	OS is defined as the time from randomization until the date of death due to any cause.
Progression-Free Survival (PFS) assessed by Investigator	Randomization up to approximately 28 months	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator or death due to any cause, whichever occurs first.
Objective Response Rate (ORR)	Randomization up to approximately 28 months	ORR is defined as the percentage of patients who achieve complete response(CR) or partial response (PR), as assessed by BICR/investigator per RECIST 1.1
Disease control rate (DCR)	Randomization up to approximately 28 months	DCR is defined as the percentage of patients who achieve CR, PR or stable disease (SD), as assessed by BICR/ investigator per RECIST 1.1
Duration of Response (DoR)	Randomization up to approximately 28 months	DoR is defined as the time from the date of first documented CR or PR until date of documented disease progression per RECIST 1.1, as assessed by BICR/investigator or death due to any cause, whichever occurs first.
Time to Response (TTR)	Randomization up to approximately 28 months	TTR is defined as the time from the date of randomization until the first documentation of CR or PR as assessed by BICR/investigator per RECIST 1.1.