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 III 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: 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 Contact: Name: Xiaoping Jin, PhD; Phone Number: 86-028-67255165; Email: jinxp@kelun.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Oriental Hospital
    • Contact: Caicun Zhou; Phone Number: 13301825532; Email: caicunzhoudr@163.com

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

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): February 5, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 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