A Study of SKB264 for the Treatment of Participants With Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

A Phase II Study of SKB264 as Monotherapy or as Combination Therapy in Subjects With Advanced or Metastatic Non-small Cell Lung Cancer

The purpose of this study is to evaluate the safety, tolerability and objective response rate of SKB264 as combination with therapy in subjects with advanced or metastatic non-small cell lung cancer.

Study Overview

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

Detailed Description

This is a multicenter, open-label study of SKB264 as combination therapy in subjects with NSCLC. Approximately up to 296 subjects will be enrolled in this study including around 36 (may expand) subjects for safety run-in period and 200 subjects for expansion period.

• Study Type: Interventional
• Enrollment (Estimated): 296
• Phase: Phase 2

Contacts and Locations

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

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Not yet recruiting
      • Beijing Cancer Hospital
      • Principal Investigator: Jun Zhao, MD
      • Contact: Han Yin
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Not yet recruiting
      • Fujian Cancer Hospital
      • Contact: Zhangzhou Huang
      • Principal Investigator: Wu Zhuang, MD
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University, Cancer Center
      • Principal Investigator: Li Zhang, MD
      • Contact: Xuemei Wu
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Not yet recruiting
      • Harbin Medical University Cancer Hospital
      • Contact: Bo Pan
      • Principal Investigator: Yan Yu, MD
  • Henan
    • Zhengzhou, Henan, China, 450018
      • Not yet recruiting
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Guang Deng
      • Principal Investigator: Xingya Li, MD
  • Hunan
    • Changsha, Hunan, China, 410013
      • Not yet recruiting
      • Hunan Cancer Hospital
      • Contact: Wusi Liu
      • Principal Investigator: Nong Yang, MD
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The First Affiliated Hospital Of NanChang University
      • Contact: Lei Xu
      • Principal Investigator: Longhua Sun, MD
  • Jilin
    • Changchun, Jilin, China, 130021
      • Not yet recruiting
      • Jilin Cancer Hospital
      • Principal Investigator: Ying Cheng, MD
      • Contact: Xiaoxin Wang
  • Liaoning
    • Shenyang, Liaoning, China, 110002
      • Not yet recruiting
      • The First Hospital of Chinese Medical University
      • Contact: Ping Yu
      • Principal Investigator: Xiujuan Qu, MD
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Not yet recruiting
      • Shanghai Chest Hospital
      • Contact: Tianqing Chu
      • Principal Investigator: Baohui Han, MD
    • Shanghai, Shanghai, China, 200123
      • Not yet recruiting
      • Shanghai East Hospital
      • Contact: Qian Chao
      • Principal Investigator: Junli Xue, MD
  • Sichuan
    • Chengdu, Sichuan, China, 610042
      • Not yet recruiting
      • Sichuan Cancer hospital
      • Contact: Yajie Zhu
      • Principal Investigator: Wenxiu Yao, MD
    • Chengdu, Sichuan, China, 610041
      • Not yet recruiting
      • West China Hospital Si Chuan University
      • Principal Investigator: Yongsheng Wang, MD
      • Contact: Huashan Shi
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Not yet recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Yanping Zhu
      • Principal Investigator: Jianya Zhou, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

1. Subjects must be at least 18 years of age on day of signing informed consent, regardless of gender;
2. Subjects with histologically or cytologically confirmed locally advanced or metastatic NSCLC ;
3. Subjects for NSCLC should be confirmed to be EGFR (Epidermal growth factor receptor) wild-type and ALK (Anaplastic lymphoma kinase) fusion gene negative; or confirmed to harbor EGFR mutation;
4. Locally advanced or metastatic NSCLC subjects without actionable EGFR mutations and ALK fusion genes, no prior systemic treatment; subjects with EGFR mutation, no prior systemic treatment or failed prior EGFR-TKI (Tyrosine kinase inhibitor) treatment;
5. Subjects are able to provide tumor blocks or slides before the first dose of study intervention;
6. Subject must have at least one radiographically measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria;
7. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1;
8. Life expectancy at least 3 months for the subject;
9. Adequate organ function;
10. Subjects must have recovered from all toxicities led by prior treatment;
11. Contraceptive methods used by male and female subjects must comply with contraceptive methods of local regulations for clinical study subjects;
12. Subjects should 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. Subjects with mixed SCLC histopathological features;
2. Subjects with a known history of prior malignancy;
3. Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or active central nervous system (CNS) metastases;
4. Subjects with ≥ Grade 2 peripheral neuropathy;
5. Subjects who had arteriovenous thromboembolic events;
6. Subjects with active inflammatory bowel disease or previous clear history of inflammatory bowel disease;
7. Subjects who suffer from cardiovascular diseases of clinical significance;
8. Subjects with a history of interstitial lung disease (ILD)/non-infectious pneumonitis that required steroids;
9. Subjects with uncontrolled systemic disease as judged by the Investigator;
10. Subjects with active autoimmune disease that required systemic treatment in the past 2 years;
11. Subjects with active hepatitis B or hepatitis C;
12. Subjects with known history of Human Immunodeficiency Virus (HIV)
13. Subjects with known active tuberculosis;
14. Subjects with known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
15. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study;
16. Subjects whose condition deteriorated rapidly, such as severe changes in performance status, during the screening process prior to the first dose of study intervention;
17. Subjects with other circumstances that, in the opinion of the Investigator, are not appropriate for participation in this study.

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

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 EGFR wild-type and ALK fusion genes negative (PD-L1 TPS ≥ 1 %); SKB264 (Dose Level 1) + Pembrolizumab	Drug: SKB264; intravenous (IV) infusion (Q2W); Drug: Pembrolizumab; intravenous (IV) infusion (400mg, Q6W); Other Names: MK-3475
Experimental: Cohort 2 EGFR wild-type and ALK fusion genes negative (PD-L1 TPS ≥ 1 %); SKB264 (Dose Level 2) + Pembrolizumab	Drug: SKB264; intravenous (IV) infusion (Q2W); Drug: Pembrolizumab; intravenous (IV) infusion (400mg, Q6W); Other Names: MK-3475
Experimental: Cohort 3 EGFR wild-type and ALK fusion genes negative; SKB264 (Dose Level 3) + Pembrolizumab + Carboplatin	Drug: SKB264; intravenous (IV) infusion (Q2W); Drug: Pembrolizumab; intravenous (IV) infusion (400mg, Q6W); Other Names: MK-3475; Drug: Carboplatin; intravenous (IV) infusion (AUC5, Q3W); Other Names: Carboplatin for injection
Experimental: Cohort 4 EGFR wild-type and ALK fusion genes negative; SKB264 (Dose Level 1) + Pembrolizumab + Carboplatin	Drug: SKB264; intravenous (IV) infusion (Q2W); Drug: Pembrolizumab; intravenous (IV) infusion (400mg, Q6W); Other Names: MK-3475; Drug: Carboplatin; intravenous (IV) infusion (AUC5, Q3W); Other Names: Carboplatin for injection
Experimental: Cohort 5 EGFR sensitizing mutation; SKB264 (Dose Level 3) + Carboplatin	Drug: SKB264; intravenous (IV) infusion (Q2W); Drug: Carboplatin; intravenous (IV) infusion (AUC5, Q3W); Other Names: Carboplatin for injection
Experimental: Cohort 6 EGFR sensitizing mutation; SKB264 (Dose Level 1) + Carboplatin	Drug: SKB264; intravenous (IV) infusion (Q2W); Drug: Carboplatin; intravenous (IV) infusion (AUC5, Q3W); Other Names: Carboplatin for injection
Experimental: Cohort 7 EGFR 19del or L858R Mutation; SKB264 (Dose Level 1) + Osimertinib	Drug: SKB264; intravenous (IV) infusion (Q2W); Drug: Osimertinib; 80mg, QD; Other Names: Osimertinib Mesylate
Experimental: Cohort 8 EGFR 19del or L858R Mutation; SKB264 (Dose Level 2) + Osimertinib	Drug: SKB264; intravenous (IV) infusion (Q2W); Drug: Osimertinib; 80mg, QD; Other Names: Osimertinib Mesylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Dose-limiting toxicity (DLT); Incidence and severity of adverse events (AEs); Discontinuation of study treatment due to AEs	From subject sign the informed consent form (ICF) to 30 days after the last dose of study treatment, up to approximately 36 months
ORR	Objective response rate (ORR) per RECIST v1.1	The proportion of subjects with a confirmed complete response (CR) or partial response (PR), up to approximately 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	For subjects with a confirmed CR or PR, DOR is defined as the time from the first documented evidence of CR or PR until radiographic disease progression or death due to any cause, whichever occurs first	From baseline until disease progression, death, or other protocol defined reason, up to approximately 36 months
Progression-free survival (PFS)	The time from first dose of study intervention to first documentation of radiographic disease progression or death due to any cause, whichever occurs first	From baseline until disease progression, death, or other protocol defined reason, up to approximately 36 months
Overall survival (OS)	the time period from the start of study intervention to death due to any cause.	From baseline until death due to any cause, up to approximately 36 months

Collaborators and Investigators

• Sponsor: Klus Pharma Inc.
• Collaborators: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): April 12, 2026

Study Registration Dates

• First Submitted: April 3, 2023
• First Submitted That Met QC Criteria: April 14, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 6, 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; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; Carboplatin; Osimertinib; Pembrolizumab
• Other Study ID Numbers: SKB264-II-04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No