A Study of SKB264 (MK-2870; Sac-TMT) for the Treatment of Participants With Advanced or Metastatic Non-small Cell Lung Cancer (SKB264-II-04) (MK-2870-003)

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: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Carboplatin; Drug: Osimertinib; Drug: SKB264

Detailed Description

This is a multicenter, open-label study of SKB264 as combination therapy or monotherapy in subjects with NSCLC. Approximately 498 subjects will be enrolled in this study including around 88 subjects for the safety run-in period and 410 subjects for the expansion period.

• Study Type: Interventional
• Enrollment (Actual): 356
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400000
      • Chongqing University Cancer Hospital (Chongqing Cancer Hospital)
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China, 510700
      • Sun Yatsen University Cancer Center Huangpu Hos
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Guangxi Cancer Hospital/ Guangxi Medical University Cancer Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin medical university cancer hospital
  • Henan
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou University(Heyi Compus)
    • Zhengzhou, Henan, China, 45008
      • Henan Cancer Hospital,Affiliated Cancer Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital of Wuhan University
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of NanChang University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
    • Changchun, Jilin, China, 130021
      • Jilin Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110002
      • The First Hospital of Chinese Medical University(Heping Compus)
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital and Institute
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai Municipality, China, 200030
      • Shanghai Chest Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 30009
      • Shanxi Provincial Cancer hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
    • Chengdu, Sichuan, China, 611130
      • Chengdu Fifth People's Hospital
    • Chengdu, Sichuan, China, 610041
      • Sichuan Cancer Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310003
      • The first Affiliated Hospital, Zhejiang University School of Medicine
• Georgia
  • Tbilisi, Georgia, 0114
    • Ltd New Hospitals
  • Tbilisi, Georgia, 0112
    • LLC "Todua Clinic"
  • Tbilisi, Georgia, 0112
    • ISR-GEO Med Res Clin Healthycore
• Romania
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400015
      • Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca
  • Dolj
    • Craiova, Dolj, Romania, 200542
      • Centrul de Oncologie Sf. Nectarie
• South Korea
  • Busan, South Korea, 48108
    • Inje University Haeundae Paik Hospital
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Gyeonggido
    • Suwon, Gyeonggido, South Korea, 16247
      • The Catholic university of Korea, St. Vincent's Hospital
  • North Chungcheong
    • Cheongju-si, North Chungcheong, South Korea, 28644
      • Chungbuk National University Hospital
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 6351
      • Samsung Medical Center
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall D Hebron
  • Barcelona, Spain, 08017
    • Micancer Center S.L.P.
  • Barcelona, Spain, 08028
    • Hospital Universitari Dexeus Grupo Quironsalud
  • Málaga, Spain, 29004
    • Hospital Quironsalud Malaga
  • Seville, Spain, 41014
    • Hospital Universitario Virgen de Valme
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro de Majadahonda
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quirónsalud Madrid
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01140
    • Medical Park Seyhan Hospital
  • Adana, Turkey (Türkiye), 01370
    • Adana City Training and Research Hospital
  • Ankara, Turkey (Türkiye), 06500
    • Gazi University Medical Faculty
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe University Medical Faculty
  • Ankara, Turkey (Türkiye), 06010
    • Gulhane Egitim ve Arastirma Hastanesi Tibbi Onkoloji Klinigi

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, tumor invasion/encasement of vital organs/vessels, risk of esophageal-tracheal/pleural fistula, or current superior vena cava syndrome;
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 1L NSCLC, EGFR/ALK negative and PD-L1 TPS ≥ 1%; SKB264 (Dose Level 1) + Pembrolizumab	Drug: Pembrolizumab; intravenous (IV) infusion (400mg, Q6W); Other Names: MK-3475; Drug: SKB264; intravenous (IV) infusion (Q2W or Q3W); Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Cohort 3 1L NSCLC, EGFR/ALK negative, regardless of PD-L1 expression level; SKB264 (Dose Level 1') + Pembrolizumab + Carboplatin	Drug: Pembrolizumab; intravenous (IV) infusion (400mg, Q6W); Other Names: MK-3475; Drug: Carboplatin; intravenous (IV) infusion (AUC5, Q3W); Other Names: Carboplatin for injection; Drug: SKB264; intravenous (IV) infusion (Q2W or Q3W); Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Cohort 4 1L NSCLC, EGFR/ALK negative, regardless of PD-L1 expression level; SKB264 (Dose Level 1'') + Pembrolizumab + Carboplatin	Drug: Pembrolizumab; intravenous (IV) infusion (400mg, Q6W); Other Names: MK-3475; Drug: Carboplatin; intravenous (IV) infusion (AUC5, Q3W); Other Names: Carboplatin for injection; Drug: SKB264; intravenous (IV) infusion (Q2W or Q3W); Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Cohort 5 NSCLC with EGFR mutation and after failure of EGFR TKI therapy; SKB264 (Dose Level 1') + Carboplatin	Drug: Carboplatin; intravenous (IV) infusion (AUC5, Q3W); Other Names: Carboplatin for injection; Drug: SKB264; intravenous (IV) infusion (Q2W or Q3W); Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Cohort 6 NSCLC with EGFR mutation and after failure of EGFR TKI therapy; SKB264 (Dose Level 1'') + Carboplatin	Drug: Carboplatin; intravenous (IV) infusion (AUC5, Q3W); Other Names: Carboplatin for injection; Drug: SKB264; intravenous (IV) infusion (Q2W or Q3W); Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Cohort 7 1L NSCLC with EGFR mutation; SKB264 (Dose Level 1) + Osimertinib	Drug: Osimertinib; 80mg, QD; Other Names: Osimertinib Mesylate; Drug: SKB264; intravenous (IV) infusion (Q2W or Q3W); Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Cohort 7-1 1L NSCLC with EGFR mutation; SKB264 (Dose Level 2) + Osimertinib	Drug: Osimertinib; 80mg, QD; Other Names: Osimertinib Mesylate; Drug: SKB264; intravenous (IV) infusion (Q2W or Q3W); Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Cohort 9 2/3L NSCLC EGFR/ALK negative; SKB264 (Dose Level 1)	Drug: SKB264; intravenous (IV) infusion (Q2W or Q3W); Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)

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): June 30, 2026
• Study Completion (Estimated): December 30, 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): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Organic Chemicals; Therapeutics; Drug Administration Routes; Drug Therapy; Coordination Complexes; Carboplatin; Injections; pembrolizumab; osimertinib
• Other Study ID Numbers: SKB264-II-04; MK-2870-003 (Other Identifier: Merck Sharp & Dohme LLC); 2023-507270-41-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No