Sacituzumab tirumotecan: 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.
Anlotinib: 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
Study 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
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Age ≥18 years, regardless of gender.
2. 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.
3. No known driver gene alterations such as EGFR, ALK, ROS1, NTRK, BRAF, MET, KRAS, HER2, RET, etc.
4. At least one measurable target lesion not previously irradiated, assessed by the investigator per RECIST v1.1.
5. ECOG performance status score of 0 or 1.
6. Asymptomatic or locally treated and stable brain metastases are allowed.
7. Life expectancy ≥ 12 weeks.
8. Adequate organ and bone marrow function.
9. Agreement to use effective medical contraception from signing informed consent until 6 months after the last dose.
10. Voluntary participation, signed informed consent, and ability to comply with the protocol.
Exclusion Criteria:
1. Tumors histologically or cytologically confirmed with mixed small cell lung cancer, squamous cell carcinoma, neuroendocrine carcinoma, or carcinosarcoma components.
2. Prior treatment with TROP2-targeted therapy or any drug targeting topoisomerase I (including ADCs).
3. Known meningeal, brainstem, spinal cord metastases and/or compression, or active central nervous system (CNS) metastases.
4. 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.).
5. 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).
6. Poorly controlled hypertension (systolic \> 160 mmHg and/or diastolic \> 100 mmHg).
7. History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid treatment, or current active/suspected ILD/pneumonitis.
8. Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or corneal disease preventing/delaying healing.
9. Active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, abdominal abscess, or acute gastrointestinal bleeding.
10. Risk of esophageal-tracheal or esophageal-pleural fistula.
11. Tumors invading major blood vessels or high risk of fatal bleeding.
12. Bleeding symptoms or any ≥CTCAE grade 3 bleeding event with unhealed wounds, ulcers, or fractures within 1 month prior to first dose.
13. Known active tuberculosis.
14. History of allogeneic organ transplant or allogeneic hematopoietic stem cell transplant.
15. HIV positive, history of AIDS, or active syphilis infection.
16. Major surgery within 4 weeks prior to dosing or planned major surgery during the study.
17. Current use of strong CYP3A4 inducers (must be avoided at least 3 weeks prior).
18. Live vaccine within 30 days prior to dosing or planned during the study.
19. Pregnant or lactating women.
20. Any condition that, in the investigator's opinion, interferes with the evaluation of the study drug or compromises subject safety.
Primary outcome measure(s)
Objective Response Rate (ORR) Assessed by Investigator per 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). 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.
Trial sites (1)
Facility
City
Region
Status
Nanfang Hospital of Southern Medical University
Guangzhou
Guangdong
More Nanfang Hospital, Southern Medical University trials in China
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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