A Study of SKB264 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

A Randomized, Open-Label, Multicenter Phase III Clinical Study of SKB264 in Combination With Pembrolizumab Versus Pembrolizumab as First-Line Treatment for PD-L1 Positive Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

The aim of the study is to evaluate the efficacy and safety of SKB264 in combination with pembrolizumab as firstline treatment for patients with PD-L1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).

Study Overview

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

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 pembrolizumab as firstline treatment for PD-L1 positive patients with locally advanced or metastatic non-small cell lung cancer.

• Study Type: Interventional
• Enrollment (Estimated): 406
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Baoding, China
    • Hebei University Affiliated Hospital
  • Beijing, China
    • Cancer Hospital Chinese Academy of Medical Sciences
  • Beijing, China
    • Beijing Institute for Cancer Research
  • Beijing, China
    • Beijing Chest Hospital. Capital Medical University
  • Changchun, China
    • Jilin Cancer Hospital
  • Changchun, China
    • The First Hospital of Jilin University
  • Changsha, China
    • Hunan Cancer Hospital
  • Changsha, China
    • Xiangya Second Hospital of Central South University
  • Changsha, China
    • The Second People's Hospital of Hunan Province（Brain Hospital of Hunan Province）
  • 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
  • Chongqing, China
    • The Southwest Hospital of Amu
  • Chongqing, China
    • Chongqing University Cancer Hospital
  • Chongqing, China
    • Army Medical Center of PLA (Daping Hospital)
  • Dalian, China
    • The Second Affiliated Hospital of Dalian Medical University
  • Dongguan, China
    • Dongguan People's Hospital
  • Fuzhou, China
    • Fujian Medical University Union Hospital
  • Fuzhou, China
    • Fujian Cancer Hospital
  • Guangzhou, China
    • Sun Yat-sen University Cancer Center
  • Guangzhou, China
    • The First Affiliated Hospital of Sun Yat-sen University
  • Guangzhou, China
    • Affiliated Cancer Hospital and Institute of Guangzhou Medical University
  • Guangzhou, China
    • Sun Yat-Sen Memorial Hospital Sun Yat-sen University
  • Hangzhou, China
    • Zhejiang Cancer Hospital
  • Hangzhou, China
    • Sir Run Run Shaw Hospital (SRRSH)
  • Harbin, China
    • The 2nd Affiliated Hospital of Harbin Medical University
  • Harbin, China
    • Harbin Medical University Cancer Hospital
  • 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 Yunnan Cancer Hospital
  • Lanzhou, China
    • Gansu Provincial 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
  • Nanjing, China
    • Jiangsu Province Hospital
  • Nanning, China
    • Guangxi Medical University Cancer Hospital
  • Nanning, China
    • People's Hospital of Guangxi Zhuang Autonomous Region
  • Shanghai, China
    • Shanghai Pulmonary Hospital
  • Shanghai, China
    • Shanghai Chest Hospital
  • Shanghai, China
    • Zhongshan Hospital of Fudan University
  • Shanghai, China
    • Shanghai East Hospital, Tongji University
  • Shaoguan, China
    • Yuebei People's Hospital
  • Shenyang, China
    • Liaoning Cancer Hospital
  • Shenyang, China
    • China Medical University First Affiliated Hospital
  • Shenyang, China
    • Shengjing Hospital, China Medical University
  • Taiyuan, China
    • Shanxi Province Cancer Hospital
  • Tianjin, China
    • Tianjin Medical University Cancer Institute and Hospital
  • Wuhan, China
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Wuhan, China
    • Hubei Cancer Hospital
  • 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
  • Xinjiang, China
    • Affiliated Tumor Hospital of Xinjiang Medical University
  • Xinxiang, China
    • The First Affiliated Hospital of Xinxiang Medical University
  • Yangzhou, China
    • Subei People's Hospital of Jiangsu province
  • Yibin, China
    • Yibin Second People's Hospital
  • Zhengzhou, China
    • The First Affiliated Hospital of Zhengzhou University
  • Zhengzhou, China
    • The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital，Henan Academy of Innovations in Medical Science
  • Zunyi, China
    • The Second Affiliated Hospital of Zunyi Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:Key Inclusion Criteria:

1. Histologically or cytologically confirmed NSCLC that is locally advanced (Stage ⅢB/ⅢC) or metastatic (Stage IV) NSCLC that is not amenable to radical surgery and/or radical radiotherapy regardless of concurrent chemotherapy.
2. No prior systemic anti-cancer therapy for locally advanced or metastatic disease.
3. Participants whose tumours are PD-L1 TPS ≥ 1%.
4. At least one measurable lesion per RECIST v1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 with no worsening within 7 days prior to randomization.
6. A life expectancy of at least 12 weeks.
7. Adequate organ and bone marrow function.

Exclusion Criteria:Key Exclusion Criteria:

1. Active second malignancy.
2. Uncontrolled or clinical significant cardiovascular disease.
3. History of noninfectious pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
4. Active infection requiring systemic therapy within 2 weeks of randomization.
5. Active hepatitis B or hepatitis C virus infection.
6. Human immunodeficiency virus (HIV) positive or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection.
7. Known allergy to SKB264 or pembrolizumab or any of its components.

8. Prior treatment with any of the following (including in the context of adjuvant, neoadjuvant therapy):

   1. Immune checkpoint inhibitors (e.g., anti-PD-1/L1 antibody, anti-CTLA-4 antibody, etc.), checkpoint agonists (e.g., ICOS, CD40, CD137, GITR, OX40 antibody, etc.), any treatment targeting the immune mechanism of tumors such as immune cell therapy;
   2. Therapy targeting TROP2.
   3. Any drug therapy that targets topoisomerase I, including antibody-drug conjugates (ADCs).
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; Participants will receive Pembrolizumab on Day 1 of each 6-week cycle.	Drug: Pembrolizumab; 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 22months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from randomization until the date of death due to any cause.	Randomization up to approximately 40 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 22months
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 22months
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 22months
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 22months
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 22months
Health-Related Quality of Life Assessment	Compare the health-related quality of life (HRQoL) of SKB264 in combination with pembrolizumab and pembrolizumab monotherapy by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire - Lung Cancer Module 13 (EORTC QLQ-LC13)	Randomization up to approximately 22months
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.
PK	PK parameters of SKB264-ADC, SKB264-TAB and free KL610023, such as maximum concentration (Cmax), minimum concentration (Cmin ), etc.	Randomization up to approximately 22months
Immunogenicity	Immunogenicity test results of SKB264	Randomization up to approximately 22months
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.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: June 3, 2024
• First Submitted That Met QC Criteria: June 3, 2024
• First Posted (Actual): June 7, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 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; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: SKB264-Ⅲ-12

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