A Randomized, Open-Label, Multicenter, Phase III Clinical Study of SKB264 in Combination With Osimertinib Versus Osimertinib Alone as First-Line Treatment for Patients With Epidermal Growth Factor Receptor (EGFR) Mutations, Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer

Official Summary

The aim of the study is to evaluate the efficacy and safety of SKB264 in combination with osimertinib as first-Line treatment for patients with epidermal growth factor receptor (EGFR) mutations, locally advanced or metastatic non-squamous non-small cell lung cancer.

Eligibility Requirements

• Minimum Age: 18 Years
• Maximum Age: 75 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 420 participants

Study Arms

• SKB264+Osimertinib (EXPERIMENTAL)
  Participants will receive SKB264 on Day 1 and Day 15 of each 4-week cycle, Osimertinib once-daily for each 4-week cycle.
• Osimertinib (ACTIVE_COMPARATOR)
  Participants will receive Osimertinib once-daily for each 4-week cycle.

Interventions

• DRUG: SKB264 — 4mg/kg, intravenous (IV) infusion
• DRUG: Osimertinib — 80mg, QD

Primary Outcomes

• Progression Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) (Randomization up to approximately 36 months)

Secondary Outcomes

• Overall Survival (OS) (Randomization up to approximately 49 months)
• Progression-Free Survival (PFS) assessed by Investigator (Randomization up to approximately 36 months)
• Objective Response Rate (ORR) (Randomization up to approximately 36 months)
• Disease control rate (DCR) (Randomization up to approximately 36 months)
• Duration of Response (DoR) (Randomization up to approximately 36 months)

Eligibility Criteria

Inclusion Criteria:

1. Aged ≥18 years to ≤75 years at the time of signing the informed consent form (ICF), regardless of gender.
2. Histologically or cytologically confirmed non-squamous NSCLC that is locally advanced (stage IIIB/IIIC) or metastatic (stage IV) non-squamous NSCLC not eligible to radical surgery and/or radical radiotherapy.
3. No prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC.
4. Histologically or cytologically confirmed EGFR-sensitive mutations.
5. Tumor tissue samples obtained at or after the diagnosis of locally advanced or metastatic tumor are eligible.
6. At least one target lesion assessed by the investigator based on RECIST v1.1.
7. ECOG performance status score of 0 or 1 within 7 days prior to randomization.
8. Life expectancy ≥ 12 weeks.
9. Adequate organ and bone marrow function.

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. Subjects who have received prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC.
3. Subjects who have received any of the following therapies (including the adjuvant/neoadjuvant therapy):

   1. Targeted TROP2 therapy;
   2. Any drug therapy that targets topoisomerase I, including antibody-drug conjugates (ADCs).
4. Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, active or central nervous system (CNS) metastase.
5. Other malignancies within 3 years prior to randomization.
6. Clinically significant abnormalities found on resting electrocardiogram (ECG)
7. Presence of any of cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors.
8. History of interstitial lung disease (ILD), drug-induced ILD, history of non-infectious pneumonitis requiring steroid treatment, current ILD or non-infectious pneumonitis.
9. Clinically severe lung injuries caused by lung diseases.
10. Unresolved toxicities from previous anti-tumor therapy to ≤ Grade 1 (based on NCI CTCAE v5.0) or the level specified in the inclusion and exclusion criteria.
11. Subjects who have received systemic corticosteroids \> 10 mg/day of prednisone or other immunosuppressive agents within 2 weeks prior to randomization.
12. Known active pulmonary tuberculosis.
13. Known history of allogeneic organ transplant and allogeneic hematopoietic stem cell transplant.
14. Presence of active hepatitis B or hepatitis C.
15. Positive result of human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection.
16. Known allergy to osimertinib, SKB264 or any of their components (including but not limited to polysorbate-20), history of severe hypersensitivity to other biologics.
17. Vaccination with live vaccines within 30 days prior to randomization, or planned vaccination with live vaccines during the study.
18. Women who are pregnant or breastfeeding.
19. Presence of local or systemic diseases caused by non-malignancies, or diseases or symptoms secondary to tumors.

Trial Locations

• Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
• Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China

Contact Information

• Xiaoping Jin PhD — CONTACT
  Phone: 86-028-67255165
  Email: jinxp@kelun.com

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