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

A Randomized, Open-Label, Multicenter Phase 3 Clinical 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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: SKB264; Drug: pemetrexed; Drug: carboplatin or cisplatin

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.

• Study Type: Interventional
• Enrollment (Estimated): 432
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking University Third Hospital
  • Beijing, China
    • Beijing Cancer Hospital
  • Beijing, China
    • Cancer Hospital Chinese Academy of Medical Sciences
  • Beijing, China
    • Beijing Chest Hospital. Capital Medical University
  • Changchun, China
    • The First Hospital of Jilin University
  • Changcun, China
    • Jilin Cancer Hospital
  • Changsha, China
    • Hunan Cancer Hospital
  • Changsha, China
    • Xiangya Hospital, Central South University
  • Changsha, China
    • Xiangya Second Hospital of Central South University
  • Chengdu, China
    • Sichuan Provincial People's Hospital
  • Chengdu, China
    • West China Hospital of Sichuan University
  • Chengdu, China
    • Chengdu Fifth People's Hospital
  • Chengdu, China
    • University of Electronic Science and Technology of China, Sichuan Cancer Hospital and Institute & Cancer, The Second People's Hospital of Sichuan Province
  • Chengdu, China
    • The General Hospital of Western Theater Command
  • Chongqing, China
    • Chongqing University Cancer Hospital
  • Chongqing, China
    • Army Medical Center of PLA (Daping Hospital)
  • Chongqing, China
    • The Second Affiliated Hospital of Army Medical University
  • Chongqing, China
    • The Southwest Hospial Of AMU
  • Dalian, China
    • The Second Affiliated Hospital of Dalian Medical University
  • Fuzhou, China
    • Fujian Cancer Hospital
  • Fuzhou, China
    • The 900 Hospital of the Joint Logistics Support Force of the People's Liberation Army of China
  • Ganzhou, China
    • First Affiliated Hospital of Gannan Medical University
  • Guangzhou, China
    • Sun Yat-sen University Cancer Center
  • Guangzhou, China
    • The First Affiliated Hospital of Guangzhou Medical University
  • Guangzhou, China
    • Affiliated Cancer Hospital and institute of Guangzhou Medical University
  • Guilin, China
    • Affiliated Hospital of Guilin Medical University
  • Hangzhou, China
    • Zhejiang Cancer Hospital
  • Hangzhou, China
    • The Second Affiliated Hospital of Zhejiang University School of Medicine
  • Hangzhou, China
    • The First Affiliated Hospital, Zhejiang University School of Medicine
  • Hangzhou, China
    • Sir Run Run Shaw Hospital (SRRSH)
  • Ha’erbin, China
    • Harbin Medical University Cancer Hospital
  • Ha’erbin, China
    • The 2nd Affiliated Hospital of Harbin Medical University
  • Hefei, China
    • The Second Affiliated Hospital of Anhui Medical University
  • Hefei, China
    • Anhui Provincial Chest Hospital
  • Jinan, China
    • Shandong Provincial Hospital
  • Jinan, China
    • Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences
  • Kunming, China
    • The Third Affiliated Hospital of Kunming Medical University
  • Lanzhou, China
    • Gansu Provincial Cancer Hospital
  • Linyi, China
    • Linyi Cancer Hospital
  • Luoyang, China
    • The First Affiliated Hospital of Henan University of Science & Technology,
  • Mianyang, China
    • Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China
  • Nanchang, China
    • The First Affiliated Hospital of Nanchang University
  • Nanchang, China
    • Jiangxi Cancer Hospital
  • Nanchong, China
    • Affiliated Hospital of North Sichuan Medical College
  • Nanjing, China
    • Jiangsu Province Hospital
  • Nanjing, China
    • Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School
  • Nanjing, China
    • Jiangsu Cancer Hospital
  • Nanning, China
    • The First Affiliated Hospital of Guangxi Medical University
  • Nanning, China
    • Guangxi Medical University Cancer Hospital
  • Nanning, China
    • People's Hospital of Guangxi Zhuang Autonomous Region
  • Neijiang, China
    • The Second People's Hospital of Neijiang
  • Qingdao, China
    • The Affiliated Hospital of Qingdao University
  • Shanghai, China
    • Shanghai Pulmonary Hospital
  • Shanghai, China
    • Shanghai Chest Hospital
  • Shanghai, China
    • Huashan Hospital Affiliated to Fudan University
  • Shanghai, China
    • Shanghai Oriental Hospital
  • Shanghai, China
    • Zhongshan Hospital of Fudan University
  • Shaoguan, China
    • Yuebei People's Hospital
  • Shengyang, China
    • Shengjing Hospital, China Medical University
  • Shenyang, China
    • Liaoning cancer hospital
  • Shenyang, China
    • China Medical University First Affiliated Hospital
  • Shijiazhuang, China
    • The Fourth Hospital of Hebei Medical University
  • Taiyuan, China
    • Shanxi Province Cancer Hospital
  • Taizhou, China
    • Taizhou Hospital of Zhejiang Province
  • Tianjin, China
    • Tianjin Medical University Cancer Institute and Hospital
  • Weifang, China
    • Weifang People'S Hospital
  • Wuhan, China
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Wuhan, China
    • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Wuhan, China
    • Hubei Cancer Hospital
  • Wuhan, China
    • Zhongnan Hospital of Wuhan University
  • Xi'an, China
    • The First Affiliated Hospital of Xian Jiaotong University
  • Xi'an, China
    • The Second Affiliated Hospital of Xian Jiaotong University
  • Xiamen, China
    • The First Affiliated Hospital of Xiamen University
  • Xiangyang, China
    • Xiangyang Central Hospital
  • Xinxiang, China
    • The First Affiliated Hospital of Xinxiang Medical University
  • Yibin, China
    • Yibin Second People's Hospital
  • Yinchuan, China
    • General Hospital of Ningxia Medical University
  • Zhengzhou, China
    • Henan Cancer Hospital
  • Zhengzhou, China
    • The First Affiliated Hospital of Zhengzhou University
  • Zunyi, China
    • The Second Affiliated Hospital Of Zunyi Medical University
  • Ürümqi, China
    • Affiliated Tumor Hospital of Xinjiang Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 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;
2. 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;
3. No prior systemic anti-cancer therapy for locally advanced or metastatic NSCLC;
4. Participants whose tumours are PD-L1 TPS < 1%;
5. At least one measurable lesion per RECIST v1.1;
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 with no worsening within 7 days prior to randomization;
7. A life expectancy of at least 12 weeks;
8. Adequate organ and bone marrow function;

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SKB264+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.	Drug: Pembrolizumab; IV Infusion; Drug: SKB264; IV Infusion
Active Comparator: Pembrolizumab+Chemotherapy; Participants will receive Pembrolizumab on Day1 of each 6-week cycle,Chemotherapy on Day1 and Day 22 of each 6-week	Drug: Pembrolizumab; IV Infusion; Drug: pemetrexed; IV Infusion; Drug: carboplatin or cisplatin; IV Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) assessed by Blinded Independent Central Review (BICR)	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.	Randomization up to approximately 28 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	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	Randomization up to approximately 28 months
Duration of Response (DoR)	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.	Randomization up to approximately 28 months
Progression-Free Survival (PFS) assessed by Investigator	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.	Randomization up to approximately 28 months
Time to Response (TTR)	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.	Randomization up to approximately 28 months
Overall Survival (OS)	OS is defined as the time from randomization until the date of death due to any cause.	Randomization up to approximately 43 months
Disease control rate (DCR)	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	Randomization up to approximately 28 months
AEs and SAEs	Incidence and severity of AEs and SAEs (per CTCAE v5.0), and clinically significant abnormal laboratory results	All AEs should be observed and recorded from the first dose until 30 days after the last dose. SAEs were observed and recorded until 90 days after the last dose of pembrolizumab or 30 days after the last dose of SKB264,whichever occurred later.
Biomarkers	Correlation between the expression level of TROP2 in tumor tissues and the efficacy.	Tumor tissue samples should be provided for TROP2 testing after subjects are eligible for screening.
Health-Related Quality of Life Assessed by EORTC QLQ-C30	The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is used to assess participants's health-related quality of life. The scale covers functional domains, symptom domains, and overall health status/total quality of life domain. All domain scores are standardized to a range of 0 to 100. For functional domains and overall health status/total quality of life, higher scores indicate better functional status and quality of life; for symptom domains, higher scores indicate more symptoms or problems (worse quality of life). This study will compare changes from baseline in quality-of-life scores across all dimensions, analyze time to deterioration in general health status, symptoms and function, and summarize the number and percentage of participants with clinically meaningful changes post-baseline.	Randomization up to approximately 28months
Lung Cancer-Related Symptoms Assessed by EORTC QLQ-LC13 Symptom Domain	The symptom domain of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (EORTC QLQ-LC13) is used to assess lung cancer-related symptoms and treatment-related symptoms. The scale includes both multiple-item and single-item measurement parameters. Scores are standardized to a range of 0 to 100. Higher scores indicate more severe symptoms (worse outcome). This study will compare changes from baseline in symptom scores, analyze time to deterioration of cancer-related symptoms, and summarize the number and percentage of participants with clinically meaningful changes post-baseline.	From randomization up to approximately 28 months
PK	PK parameters of SKB264-ADC, SKB264-TAB and free KL610023, such as maximum concentration (Cmax), minimum concentration (Cmin ), etc.	Randomization up to approximately 28months
Immunogenicity	Anti-drug antibody (ADA) of SKB264 in the serum of subjects will be determined using MSD-based Bridging-ECLA.	Randomization up to approximately 28months

Collaborators and Investigators

• Sponsor: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 22, 2024
• First Submitted That Met QC Criteria: November 27, 2024
• First Posted (Actual): December 2, 2024

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Platinum Compounds; Pemetrexed; Carboplatin; Cisplatin; pembrolizumab
• Other Study ID Numbers: SKB264-Ⅲ-14

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No