Second-Line Sacituzumab Tirumotecan Plus Anlotinib for Advanced Driver Gene-Negative Non-Squamous NSCLC

NCT07703228 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: NFEC-2025-641
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate whether sacituzumab govitecan (TROP2 antibody-drug conjugate) in combination with anlotinib (multi-target tyrosine kinase inhibitor) can improve treatment efficacy and safety in patients with driver gene-negative locally advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) after failure of first-line immunotherapy combined with platinum-based chemotherapy. The main questions it aims to answer are: Can the combination of sacituzumab govitecan and anlotinib improve progression-free survival (PFS) compared to historical second-line chemotherapy outcomes? What is the objective response rate (ORR) and safety profile of this combination therapy in this patient population? Can baseline multi-omics biomarkers (metabolomics, proteomics, and ctDNA genomics) predict response or resistance to sacituzumab govitecan? If there is a comparison group: This is an exploratory single-arm study, and outcomes will be compared with historical controls of second-line chemotherapy in similar patient populations. Participants will: Receive sacituzumab govitecan combined with anlotinib according to the study treatment schedule Undergo routine imaging evaluations to assess tumor response Provide peripheral blood samples before treatment for metabolomic, proteomic, and ctDNA genomic analyses Be monitored regularly for treatment response and adverse events

Conditions

NSCLC (Advanced Non-small Cell Lung Cancer); NSCLC Stage IIIB~IV; Second-line Therapy; Metastases

Keywords

Non-squamous non-small cell lung cancer; NSCLC; EGFR wild type; ALK negative; Advanced NSCLC; Second-line treatment; Sacituzumab tirumotecan; Anlotinib

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Assessed by Investigator per RECIST v1.1

  The objective response rate (ORR) is defined as the proportion of subjects with Complete Response (CR) or Partial Response (PR) out of the total subjects, assessed by the investigator according to RECIST v1.1.

  Up to 2 years (Assessed every 6 weeks for the first 48 weeks, then every 12 weeks thereafter until disease progression or death).

Study Arms (1)

Sacituzumab Tirumotecan + Anlotinib

EXPERIMENTAL

Patients in this arm receive Sacituzumab Tirumotecan administered via intravenous (IV) infusion at a dose of 4 mg/kg on Day 1 of each 14-day cycle (Q2W). Patients concurrently receive Anlotinib administered orally (PO) at a dose of 10 mg once daily before breakfast on Days 1 through 14 of each 21-day cycle (Q3W). The combination treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria are met.

Drug: Sacituzumab tirumotecan; Drug: Anlotinib

Interventions

Sacituzumab tirumotecan DRUG

Sacituzumab Tirumotecan is administered via intravenous (IV) infusion at a dose of 4 mg/kg on Day 1 of each 14-day cycle (Q2W). The treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria are met.

Sacituzumab Tirumotecan + Anlotinib

Anlotinib DRUG

Anlotinib is administered orally (PO) at a dose of 10 mg once daily before breakfast on Days 1 through 14 of each 21-day cycle (Q3W). The treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria are met

Sacituzumab Tirumotecan + Anlotinib

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years, regardless of gender.
• Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-squamous NSCLC, progressing after prior anti-PD-1/L1 monoclonal antibody combined with platinum-based doublet chemotherapy.
• No known driver gene alterations such as EGFR, ALK, ROS1, NTRK, BRAF, MET, KRAS, HER2, RET, etc.
• At least one measurable target lesion not previously irradiated, assessed by the investigator per RECIST v1.1.
• ECOG performance status score of 0 or 1.
• Asymptomatic or locally treated and stable brain metastases are allowed.
• Life expectancy ≥ 12 weeks.
• Adequate organ and bone marrow function.
• Agreement to use effective medical contraception from signing informed consent until 6 months after the last dose.
• Voluntary participation, signed informed consent, and ability to comply with the protocol.

You may not qualify if:

• Tumors histologically or cytologically confirmed with mixed small cell lung cancer, squamous cell carcinoma, neuroendocrine carcinoma, or carcinosarcoma components.
• Prior treatment with TROP2-targeted therapy or any drug targeting topoisomerase I (including ADCs).
• Known meningeal, brainstem, spinal cord metastases and/or compression, or active central nervous system (CNS) metastases.
• Other malignancies within 3 years prior to dosing (except locally cured tumors like basal cell carcinoma, squamous cell carcinoma of the skin, cervical carcinoma in situ, etc.).
• Presence of major cardiovascular diseases or risk factors within 6 months prior to dosing (e.g., myocardial infarction, severe arrhythmias, active myocarditis, major vascular disease requiring surgery).
• Poorly controlled hypertension (systolic \> 160 mmHg and/or diastolic \> 100 mmHg).
• History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid treatment, or current active/suspected ILD/pneumonitis.
• Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or corneal disease preventing/delaying healing.
• Active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, abdominal abscess, or acute gastrointestinal bleeding.
• Risk of esophageal-tracheal or esophageal-pleural fistula.
• Tumors invading major blood vessels or high risk of fatal bleeding.
• Bleeding symptoms or any ≥CTCAE grade 3 bleeding event with unhealed wounds, ulcers, or fractures within 1 month prior to first dose.
• Known active tuberculosis.
• History of allogeneic organ transplant or allogeneic hematopoietic stem cell transplant.
• HIV positive, history of AIDS, or active syphilis infection.

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead
• Shenzhen Hospital, Guangzhou University of Chinese Medicine: collaborator
• The Central Hospital of Huanggang: collaborator
• Department of Obstetrics and Gynecology, Affiliated Dongguan People's Hospital, Southern Medical University: collaborator
• Affiliated Cancer Hospital & Institute of Guangzhou Medical University: collaborator

Study Sites (1)

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: May 28, 2026
• First Posted: July 14, 2026
• Study Start: August 13, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): March 13, 2028
• Last Updated: July 14, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will become available beginning 6 months and ending 36 months following the publication of the primary study results
• Access Criteria: Data will be shared with researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose, and who provide a methodologically sound research proposal. Proposals should be directed to the corresponding author (Principal Investigator). To gain access, data requestors will need to sign a data access agreement

Locations

CN (1)