A Phase III Study of SKB264 for EGFR Mutant NSCLC Patients

A Randomized, Open-Label, Multicenter Phase 3 Study to Evaluate SKB264 Monotherapy Versus Pemetrexed in Combination With Platinum in Patients With Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer With EGFR Mutation Who Have Failed to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Therapy

This is a randomized, open-label, multicenter Phase 3 clinical study to evaluate SKB264 monotherapy versus pemetrexed in combination with platinum in subjects with locally advanced or metastatic non-squamous NSCLC with EGFR mutation who have failed to EGFR-TKI therapy.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: SKB264; Drug: Pemetrexed; Drug: Carboplatin; Drug: Cisplatin

Detailed Description

This is a randomized, open-label, multicenter Phase 3 clinical study to evaluate SKB264 monotherapy versus pemetrexed in combination with platinum in subjects with locally advanced or metastatic non-squamous NSCLC with EGFR mutation who have failed to EGFR-TKI therapy. The primary objective is to compare the efficacy and safety of SKB264 monotherapy versus pemetrexed in combination with platinum in patients with locally advanced or metastatic non-squamous NSCLC with EGFR mutation who have failed to EGFR-TKI therapy.

• Study Type: Interventional
• Enrollment (Estimated): 356
• Phase: Phase 3

Contacts and Locations

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

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-Sen University Cancer Center
      • Contact: Li Zhang, PHD; Phone Number: 020-87343458; Email: zhangli@sysucc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Males or females aged ≥18 to ≤75 years at the time of signing the ICF;
2. Histologically or cytologically confirmed non-squamous NSCLC and locally advanced (stage IIIB/IIIC) or metastatic (Stage IV) non-squamous NSCLC not amenable to radical surgery and/or radical concurrent/sequential chemoradiotherapy;
3. EGFR-sensitive mutations;
4. Failure of prior EGFR-TKI therapy;
5. At least one measurable target lesion per RECIST 1.1 as assessed by the investigator;
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
7. Expected survival ≥12 weeks;
8. Adequate organ and bone marrow function;
9. Female subjects of childbearing potential and male subjects with partners of childbearing potential who use effective medical contraception from the time of signing the informed consent form until 6 months after the last dose;
10. Subjects voluntarily participate in the study, sign the ICF, and will be able to comply with the protocol-specified visits and relevant procedures

Exclusion Criteria:

1. Histologically or cytologically confirmed presence of small cell lung cancer, neuroendocrine carcinoma, and carcinosarcoma components or squamous cell carcinoma components of more than 10%;
2. Other malignancies within 3 years prior to the first dose;
3. History of (noninfectious) interstitial lung disease (ILD)/noninfectious pneumonitis requiring steroid therapy and current ILD/noninfectious pneumonitis;
4. Subjects with active chronic inflammatory bowel disease, GI tract obstruction, severe ulcers, perforation gastrointestinal, abdominal abscess, or acute GI tract bleed;
5. Toxicities from prior anti-tumor therapy not recovering to ≤ Grade 1 (per NCI CTCAE 5.0) or to the level specified in the eligibility criteria;
6. Subjects with human immunodeficiency virus (HIV) test positive or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection;
7. Prior TROP2-targeted therapy;
8. Prior treatment with any drug therapy targeting topoisomerase I inhibitor, including antibody-drug conjugates (ADCs);
9. Major surgery within 4 weeks prior to the first dose or expected to require major surgery during the study;
10. Subjects who have received live vaccines within 30 days prior to the first dose, or are scheduled to receive live vaccines during the study;
11. 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 by IV infusion on Days 1 and 15 of each 4-week cycle;	Drug: SKB264; intravenous (IV) infusion (Q2W)
Active Comparator: pemetrexed+ carboplatin or on Day 1 of each 3-week cycle, with 4 cycles chemo	Drug: Pemetrexed; 500 mg/m2 intravenous (IV) infusion (Q3W); Drug: Carboplatin; AUC 5 intravenous (IV) infusion (Q3W) 4cycles; Drug: Cisplatin; 75 mg/m2 intravenous (IV) infusion (Q3W) 4cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS assessed by BIRC per RECIST 1.1	From baseline until disease progression, death, or other protocol defined reason,up to approximately 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall survival (OS)	From the date of randomization to the date of death due to any cause. Up to 2 years.
Progression-free survival (PFS)	PFS assessed by the investigator per RECIST 1.1	From baseline until disease progression, death, or other protocol defined reason,up to approximately 36 months
Objective response rate(ORR)	ORR assessed by the investigator and BIRC per RECIST 1.1	Up to 2 years
Disease control rate(DCR)	DCR assessed by the investigator and BIRC per RECIST 1.1	Up to 2 years
Duration of response(DOR)	DOR assessed by the investigator and BIRC per RECIST 1.1	From baseline until disease progression, death, or other protocol defined reason, up to approximately 36 months
Time to response(TTR)	TTR assessed by the investigator and BIRC per RECIST 1.1	Up to 2 years
AEs and SAEs	Incidence and severity of AEs and SAEs (per CTCAE 5.0), and clinically significant abnormal laboratory findings	AEs should be observed and recorded from signing the ICF until 30 days after the last dose. AEs occurring 30 days after the last dose are not required to be actively collected by the investigator.
Mean change from baseline in the European Organisation for Research and Treatment of Cancer (EORTC) 30-item core quality-of-life questionnaire (QLQ-C30）	To assess the impact of SKB264 on disease related symptoms and health related quality of life (HRQoL) in this patient population.	Up to 2 years
Mean change from baseline in the European Organisation for Research and Treatment of Cancer (EORTC) complementary 13-item quality-of-life questionnaire - lung cancer symptoms questionnaire (QLQ-LC13)	To assess the impact of SKB264 on disease related symptoms and health related quality of life (HRQoL) in this patient population	Up to 2 years

Collaborators and Investigators

• Sponsor: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.
• Collaborators: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2023
• Primary Completion (Estimated): May 20, 2025
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: April 18, 2023
• First Submitted That Met QC Criteria: May 11, 2023
• First Posted (Actual): May 23, 2023

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Carboplatin; Pemetrexed
• Other Study ID Numbers: SKB264-Ⅲ-09

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