Clinical trial NCT05870319: A Phase III Study of SKB264 for EGFR Mutant NSCLC Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
First posted: 2023-05-23
Enrollment: 356
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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;

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From baseline until disease progression, death, or other protocol defined reason,up to approximately 36 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: From the date of randomization to the date of death due to any cause. Up to 2 years.
measure: Progression-free survival (PFS)
timeFrame: From baseline until disease progression, death, or other protocol defined reason,up to approximately 36 months
measure: Objective response rate(ORR)
timeFrame: Up to 2 years
measure: Disease control rate(DCR)
timeFrame: Up to 2 years
measure: Duration of response(DOR)
timeFrame: From baseline until disease progression, death, or other protocol defined reason, up to approximately 36 months
measure: Time to response(TTR)
timeFrame: Up to 2 years
measure: AEs and SAEs
timeFrame: 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.
measure: Mean change from baseline in the European Organisation for Research and Treatment of Cancer (EORTC) 30-item core quality-of-life questionnaire (QLQ-C30）
timeFrame: Up to 2 years
measure: 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)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
References: