Efficacy and Safety of SKB264 Plus Anlotinib in EGFR-TKI-Resistant Advanced NSCLC With Liver Metastasis

NCT07545213 | Not Yet Recruiting Phase 2

• 1 other identifier: KY-2026-059
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if the combination therapy with SKB264 and anlotinib works to treat EGFR-TKI-resistant, liver-metastatic non-squamous non-small cell lung cancer (NSCLC). It will also learn about the safety of the combination therapy with SKB264 and anlotinib. The main questions it aims to answer are: Does combination therapy with SKB264 and anlotinib increase response rate and disease control rate, prolong duation of response and progressioin-free survival. What medical problems do participants have when taking combination therapy with SKB264 and anlotinib? Researchers will compare combination therapy with SKB264 and anlotinib to a historical data (the response rate of other drugs reported in literature) to see if combination therapy with SKB264 and anlotinib works better to treat EGFR-TKI-resistant, liver-metastatic non-squamous non-small cell lung cancer (NSCLC). Participants will:

1. 1.receive SKB264 4 mg/kg intravenously on a 14-day cycle, and take anti-H1/H2 antihistamines, acetaminophen, and dexamethasone is recommended before infusion for the first 4 infusions to prevent side effects; the regimen may be simplified starting from the 5th infusion.
2. 2.take anlotinib 10 mg orally once daily for 14 consecutive days, followed by a 7-day rest period.
3. 3.Visit the clinic once every week for checkups and tests

Conditions

Non-small Cell Lung Cancer; EGFR Mutant Advanced Non-small Cell Lung Cancer

Keywords

non-small cell lung cancer; NSCLC; EGFR-TKI resistance; SKB264; anlotinib

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective response rate is defined as the proportion of subjects who achieve a best overall response of complete response (CR) or partial response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  From first dose of study treatment until disease progression or last evaluable assessment, assessed every 6-12 weeks depending on treatment phase, up to approximately 24 months.

Secondary Outcomes (7)

• Disease Control Rate (DCR)

  From first dose of study treatment until disease progression or last evaluable assessment, assessed every 6-12 weeks depending on treatment phase, up to approximately 24 months.

• Duration of Response (DOR)

  From first documented response to disease progression or death, assessed every 6-12 weeks during treatment, up to approximately 24 months.

• Time to Response (TTR)

  From first dose to first documented response, assessed every 6-12 weeks during treatment, up to approximately 12 months.

• Progression-Free Survival (PFS)

  From first dose to disease progression or death, assessed every 6-12 weeks during treatment, up to approximately 24 months.

• Overall Survival (OS)

  From first dose to death, assessed during safety follow-up and survival follow-up visits every 12 weeks, up to approximately 36 months.

Study Arms (1)

SKB264 plus anlotinib

EXPERIMENTAL

SKB264 4 mg/kg intravenously on a 14-day cycle; anlotinib 10 mg orally once daily for 14 consecutive days, followed by a 7-day rest period.

Drug: SKB264

Interventions

SKB264 DRUG

SKB264 4 mg/kg intravenously on a 14-day cycle, and take anti-H1/H2 antihistamines, acetaminophen, and dexamethasone is recommended before infusion for the first 4 infusions to prevent side effects; the regimen may be simplified starting from the 5th infusion. anlotinib 10 mg orally once daily for 14 consecutive days, followed by a 7-day rest period.

Also known as: Anlotinib

SKB264 plus anlotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible for this study, participants must meet all of the following criteria:
• Aged ≥ 18 years, both male and female;
• ECOG performance status score of 0-1;
• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) that is locally advanced (stage IIIB/IIIC) or metastatic (stage IV) and not amenable to curative surgery and/or curative radiotherapy (with or without concurrent chemotherapy), according to the IASLC 9th edition lung cancer TNM staging system.
• At least one measurable target lesion in the liver (according to RECIST version 1.1);
• Has previously received EGFR-TKI therapy for locally advanced or metastatic NSCLC with treatment failure (radiographic disease progression)；
• Life expectancy ≥12 weeks.
• Adequate organ and bone marrow function (without receiving blood transfusion, recombinant human thrombopoietin, or colony-stimulating factor therapy within 2 weeks prior to the first dose), defined as follows:
• Complete blood count: absolute neutrophil count (NEUT#) ≥ 1.5 × 10⁹/L; platelet count (PLT) ≥ 100 × 10⁹/L; hemoglobin ≥ 9 g/dL;
• Liver function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≤ 2.5 × upper limit of normal (ULN); total bilirubin (TBIL) ≤ 1.5 × ULN;
• Renal function: creatinine clearance (Ccr) ≥ 60 mL/min (Cockcroft-Gault formula see appendix);
• Cardiac function: left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiography (ECHO) or multigated acquisition (MUGA) scan;
• Female participants of childbearing potential and male participants with partners of childbearing potential must use a medically approved contraceptive method (e.g., intrauterine device, contraceptive pills, or condoms) during the study treatment period and for 6 months after the last dose;
• Participants voluntarily enroll in this study, sign the informed consent form, have good compliance, and cooperate with follow-up visits.

You may not qualify if:

• Participants who meet any of the following criteria will not be enrolled in this study:
• Histologically or cytologically confirmed presence of small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma components;
• Previous treatment with TROP2-targeted therapy and/or topoisomerase I inhibitors;
• Has had other malignant tumors within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin;
• Known or screening-detected symptomatic active central nervous system (CNS) metastases or carcinomatous meningitis (Note: ① Patients who have been treated and have stable disease for ≥4 weeks and have discontinued systemic corticosteroids (at any dose) for \>3 days may be enrolled. ② Patients with asymptomatic brain metastases (i.e., no neurological symptoms, no requirement for corticosteroids, and no lesion \>1.5 cm) are eligible but require regular brain imaging as part of disease site evaluation)；
• Known history of allergy to the study drugs or their components, history of immunodeficiency, or history of organ transplantation;
• History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid treatment; current ILD or non-infectious pneumonitis; or suspected ILD or non-infectious pneumonitis that cannot be ruled out by imaging at screening; clinically severe pulmonary impairment due to concurrent pulmonary diseases, including but not limited to any underlying pulmonary disease (e.g., pulmonary embolism within 3 months prior to dosing, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.) or any autoimmune, connective tissue, or inflammatory disease that may affect the lungs (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.), or prior pneumonectomy;
• Active infection requiring systemic therapy within 2 weeks prior to the first dose;
• According to the investigator's judgment, presence of concomitant diseases that seriously jeopardize patient safety or affect the patient's ability to complete the study, including but not limited to hypertension uncontrolled by medication, severe diabetes, active infection, etc;
• Occurrence of arterial/venous thrombotic events, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism, within 12 weeks prior to signing the informed consent form;
• Current active bleeding, or central lung cancer with potential for massive hemorrhage; or history of bleeding disorders (e.g., von Willebrand disease or hemophilia); clinically significant bleeding within 6 months prior to enrollment (e.g., gross hematuria, gastrointestinal bleeding, and hemoptysis); or receipt of therapeutic anticoagulants or aspirin within 14 days prior to enrollment;
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment, or minor surgical procedure within 7 days prior to enrollment;
• Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or a history of corneal disease that prevents or delays corneal healing;
• Any other conditions that, in the investigator's opinion, make the patient unsuitable for participation in this study.

Sponsors & Collaborators

• The Fourth Affiliated Hospital of Zhejiang University School of Medicine: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (1)

The Fourth Affiliated Hospital of Zhejiang University, School of Medicine

Yiwu, Zhejiang, 322000, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

anlotinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Kai Wang, MD, PhD

  The Fourth Affiliated Hospital of Zhejiang University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

chengying Kong, MM

CONTACT

18358962596; kongchengying@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2026
• First Posted: April 22, 2026
• Study Start: April 20, 2026
• Primary Completion (Estimated): February 15, 2028
• Study Completion (Estimated): August 15, 2028
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

CN (1)