A Phase III Study of SKB264 for EGFR Mutant NSCLC Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: SKB264
* Drug: Pemetrexed
* Drug: Carboplatin
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged ≥18 to ≤75 years at the time of signing the ICF; 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; EGFR-sensitive mutations; Failure of prior EGFR-TKI therapy; At least one measurable target lesion per RECIST 1.1 as assessed by the investigator; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Expected survival ≥12 weeks; Adequate organ and bone marrow function; 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; 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: Histologically or cytologically confirmed presence of small cell lung cancer, neuroendocrine carcinoma, and carcinosarcoma components or squamous cell carcinoma components of more than 10%; Other malignancies within 3 years prior to the first dose; History of (noninfectious) interstitial lung disease (ILD)/noninfectious pneumonitis requiring steroid therapy and current ILD/noninfectious pneumonitis; Subjects with active chronic inflammatory bowel disease, GI tract obstruction, severe ulcers, perforation gastrointestinal, abdominal abscess, or acute GI tract bleed; 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; Subjects with human immunodeficiency virus (HIV) test positive or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection; Prior TROP2-targeted therapy; Prior treatment with any drug therapy targeting topoisomerase I inhibitor, including antibody-drug conjugates (ADCs); Major surgery within 4 weeks prior to the first dose or expected to require major surgery during the study; Subjects who have received live vaccines within 30 days prior to the first dose, or are scheduled to receive live vaccines during the study; Pregnant or lactating women;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SKB264 by IV infusion on Days 1 and 15 of each 4-week cycle;<br> | Drug: SKB264<br>* intravenous (IV) infusion (Q2W)<br>|
| Active Comparator: pemetrexed+ carboplatin or on Day 1 of each 3-week cycle, with 4 cycles chemo<br> | Drug: Pemetrexed<br>* 500 mg/m2 intravenous (IV) infusion (Q3W)<br>Drug: Carboplatin<br>* AUC 5 intravenous (IV) infusion (Q3W) 4cycles<br>Drug: Cisplatin<br>* 75 mg/m2 intravenous (IV) infusion (Q3W) 4cycles<br>|

What is the study measuring?
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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 |