Sacituzumab Tirumotecan in Combination With Anlotinib in Previously Treated Patients With Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (STAR-01)

Sacituzumab Tirumotecan in Combination With Anlotinib in Previously Treated Patients With Extensive-Stage Small Cell Lung Cancer (ES-SCLC): A Prospective, Single-Arm, Phase II Study (STAR-01)

This is an single-arm, multicenter phase II study to evaluate the safety and efficacy of Sacituzumab Tirumotecan (sac-TMT) plus anlotinib in previously treated extensive-stage small cell lung cancer (ES-SCLC). The study is expected to enroll up to 33 eligible patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Extensive-stage Small Cell Lung Cancer (ES-SCLC)
• Intervention / Treatment: Drug: Sacituzumab Tirumotecan and Anlotinib

Detailed Description

Extensive-stage small cell lung cancer (ES-SCLC) is among the most aggressive lung cancer subtypes, with rapid progression and poor prognosis. Despite first-line immunotherapy plus chemotherapy improving outcomes, most patients relapse within one year and face limited options. Topotecan, the standard second-line therapy, yields only 10-20% ORR and median PFS of ~3 months. Therefore, identifying novel therapeutic strategies with improved efficacy in ES-SCLC represent an urgent unmet medical need.

Sacituzumab tirumotecan, a structurally optimized Trop-2-directed ADC, and anlotinib, a multi-target TKI inhibiting VEGFR, FGFR, and MET, offer complementary mechanisms of action. We hypothesize that their combination may synergistically overcome acquired resistance to chemotherapy and immunotherapy, providing a novel therapeutic strategy for previously treated ES-SCLC.

Eligible participants will receive Sacituzumab Tirumotecan (4mg/Kg intravenously on Day 1, Q2W) plus Anlotinib (8 mg orally once daily on Days 1-14, Q3W). The primary objective is Objective Response Rate (ORR), and the secondary objectives including but not limited Progression-Free Survival (PFS), Overall Survival (OS) and Disease control response (DCR) .

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jianxin Xue; Phone Number: 86-028-85423581; Email: radjianxin@163.com
• Study Contact Backup: Name: You Lu; Phone Number: +86 189 8060 1763; Email: radyoulu@hotmail.com

Study Locations

• China
  • Chengdu
    • Sichuan, Chengdu, China, 610041
      • West China Hospital of Sichuan University
      • Contact: Jianxin Xue; Phone Number: 86-028-85423581; Email: radjianxin@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1.Voluntary participation with written informed consent obtained prior to any study-specific procedures.
• 2.Age ≥ 18 years and ≤ 75 years, regardless of sex.
• 3.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 4.Life expectancy of at least 3 months.
• 5.Histologically or cytologically confirmed small cell lung cancer (SCLC) based on pathology and immunohistochemistry/immunophenotyping results; disease staged as extensive-stage SCLC (ES-SCLC) according to the Veterans Administration Lung Study Group (VALG) staging system.
• 6.Disease progression (at the time of enrollment) after at least two cycles of platinum-based systemic therapy with or without PD-1/L1 inhibitors; no more than two prior lines of therapy.

Note: Adjuvant therapy is considered one prior line if disease progression occurs during treatment or within 6 months of the last adjuvant dose.

• 7.At least one measurable lesion as defined by RECIST version 1.1. Lesions previously treated with local therapy may be considered target lesions only if progression has been clearly documented at that site post-treatment. Brain lesions as sole target lesions are not acceptable.
• 8.Adequate bone marrow function without transfusion or growth factor support within 14 days prior to screening: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count ≥ 100 × 10⁹/L; Hemoglobin ≥ 90 g/L.
• 9.Adequate hepatic function: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), or ≤ 2 × ULN for patients with Gilbert's syndrome; TBIL ≤ 3.0 × ULN is permitted if direct bilirubin suggests extrahepatic obstruction. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN (or ≤ 5 × ULN in the presence of liver metastases).
• 10.Adequate renal function: Creatinine (Cr) ≤ 1.5 × ULN and creatinine clearance (Ccr) ≥ 50 mL/min (calculated by Cockcroft-Gault formula or other clinically validated method).
• 11.Adequate coagulation function: Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; International normalized ratio (INR) ≤ 1.5 × ULN;
• 12.Adequate cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50% assessed by echocardiography within 28 days prior to enrollment. New York Heart Association (NYHA) classification < 3.
• 13.Female patients of childbearing potential must agree to use medically effective contraception from the time of signing informed consent until 6 months after the last dose of study treatment.

Exclusion Criteria:

• 1.History of other primary malignancies within 5 years prior to signing informed consent, except for: radically treated malignancies with no recurrence within 5 years; adequately treated non-melanoma skin cancer, cervical carcinoma in situ, thyroid cancer, or other malignancies considered cured.
• 2.Prior pathological diagnosis of combined small cell lung cancer (e.g., mixed SCLC and NSCLC), transformed NSCLC (SCLC transformed to NSCLC), or transformed SCLC (NSCLC transformed to SCLC).
• 3.Prior anti-tumor therapy within specified washout periods before first study dose: chemotherapy, radiotherapy, biologics, endocrine therapy, immunotherapy within 4 weeks; topical anti-tumor agents within 5 half-lives; nitrosoureas or mitomycin C within 6 weeks; oral fluoropyrimidines or small-molecule targeted agents within 5 half-lives; anti-tumor traditional Chinese medicine within 2 weeks.
• 4.Treatment with any other investigational drug or therapy within 4 weeks prior to first study dose.
• 5.Prior or current use of topoisomerase I inhibitors, including antibody-drug conjugates with topoisomerase I inhibitor payloads (e.g., topotecan, irinotecan, trastuzumab deruxtecan, sacituzumab govitecan, datopotamab deruxtecan [DS-1062]).
• 6.Brain metastases unless asymptomatic (stable for ≥4 weeks, requiring ≤10 mg/day prednisone or equivalent for ≥14 days prior to first dose, and no significant peritumoral edema on imaging); leptomeningeal or brainstem metastases; spinal cord compression (radiographically confirmed, symptomatic or asymptomatic); bone marrow metastases.
• 7.Imaging evidence of tumor lesions located ≤5 mm from major blood vessels, invading major vessels, or assessed by the investigator as having high risk of major bleeding during the study.
• 8.History of deep vein or arterial thromboembolic events within 6 months (e.g., cerebrovascular accident including TIA, deep vein thrombosis, pulmonary embolism); DVT adequately treated or superficial vein thrombosis with low bleeding risk per investigator may be enrolled.
• 9.Prior treatment-related toxicities (CTCAE v5.0) ≥ Grade 2, except for alopecia, residual neurotoxicity, or stable hypothyroidism on hormone replacement.
• 10.Major surgery (excluding biopsy or vascular access) or significant trauma within 4 weeks prior to first study dose, or planned elective surgery during the study period.
• 11.Receipt of live or live-attenuated vaccines within 4 weeks prior to first study dose.
• 12.Systemic corticosteroids (prednisone >10 mg/day or equivalent) or other immunosuppressive agents within 14 days prior to first study dose, except for: topical, ocular, intra-articular, intranasal, or inhaled corticosteroids; short-term corticosteroids for prophylaxis (e.g., contrast allergy).
• 13.History of non-infectious interstitial lung disease/pneumonitis requiring steroid maintenance (requiring 14-day washout), current ILD, or suspected ILD not ruled out by imaging at screening.
• 14.Active tuberculosis; active or uncontrolled autoimmune disease; acquired or congenital immunodeficiency disorders; history of allogeneic stem cell, bone marrow, or solid organ transplantation.
• 15.Serious infection within 4 weeks prior to first study dose, including but not limited to infection requiring systemic antibiotics, bacteremia, or severe pneumonia.
• 16.Positive serology results: HIV antibody positive; untreated active hepatitis B (HBsAg positive with HBV-DNA > ULN); Note: Patients meeting certain criteria may be enrolled with antiviral prophylaxis/monitoring; HCV-Ab positive with detectable HCV-RNA.
• 17.Significant cardiovascular disease history, including but not limited to: severe cardiac arrhythmia or conduction abnormalities (e.g., requiring intervention, Mobitz II or third-degree AV block); QTcF >450 ms (male) or >470 ms (female); congestive heart failure (NYHA class ≥II), unstable angina, acute coronary syndrome, aortic dissection, stroke or TIA within 6 months; deep vein thrombosis or pulmonary embolism within 6 months (excluding catheter-related or superficial thrombosis); uncontrolled hypertension (systolic >160 mmHg and/or diastolic >100 mmHg).
• 18.Clinically uncontrolled third-space fluid collections (e.g., pleural or ascitic effusion requiring intervention; patients with stable effusions >1 week post-drainage may enroll); pericardial effusion (asymptomatic minimal effusion not requiring intervention may enroll). If intra-cavity anti-tumor agents were used, a washout of ≥5 half-lives or 4 weeks (whichever is shorter) is required.
• 19.Known hypersensitivity or delayed allergic reaction to any component of the study drugs or comparators (e.g., topotecan, irinotecan, paclitaxel monotherapy).
• 20.Substance abuse, alcohol/drug dependence, or any medical condition (e.g., anxiety, depression) that may interfere with study participation or outcomes per investigator judgment.
• 21.Pregnant or breastfeeding women; men or women planning to conceive during the study.
• 22.Expected poor compliance, or any other severe systemic disease or condition that, in the investigator's opinion, makes the patient unsuitable for this study.
• 23.Bleeding diathesis (e.g., active peptic ulcer) or requirement for anticoagulants/vitamin K antagonists (e.g., warfarin, heparin); low-dose prophylactic warfarin (≤1 mg/d), heparin (≤12,000 U/d), or aspirin (≤100 mg/d) permitted if INR ≤1.5. Imaging evidence of tumor invasion, significant necrosis, or cavitation with high bleeding risk per investigator.
• 24.Any severe or uncontrolled systemic disease, including but not limited to: active tuberculosis/pulmonary fibrosis; active or uncontrolled infection requiring systemic therapy; clinically active diverticulitis, intra-abdominal abscess, GI obstruction; liver disease (e.g., cirrhosis, decompensated liver disease, acute/chronic hepatitis); poorly controlled diabetes (two consecutive FBG >10 mmol/L); urine protein ≥2+ confirmed by 24-hour urine protein >1.0 g; uncontrolled hypercalcemia (>1.5 mmol/L ionized calcium or >12 mg/dL calcium or corrected serum calcium >ULN) or symptomatic hypercalcemia requiring bisphosphonates; non-healing wounds or fractures; psychiatric disorders interfering with treatment compliance.
• 25.Factors affecting oral drug absorption (e.g., inability to swallow, post-, chronic diarrhea, intestinal obstruction).
• 26.Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or history of corneal disease affecting/delaying corneal healing.
• 27.Any other condition deemed unsuitable for participation by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental Arm; Participants will receive sacituzumab tirumotecan in combination with anlotinib. Sacituzumab tirumotecan will be administered intravenously, and anlotinib will be administered orally, according to the dosing schedule specified in the study protocol. The treatment will continue until disease progression, unacceptable toxic effects, withdrawal from the trial, or death or other protocol-defined discontinuation criteria are met, whichever occurred first.

Drug: Sacituzumab Tirumotecan and Anlotinib; Treatment with Sacituzumab Tirumotecan (4mg/kg IV d1 Q2W) and Anlotinib (8mg po d1-14 Q3W) until confirmed by the investigator as imaging disease progression, intolerable toxicity, subject's request to terminate treatment, or other treatment termination criteria specified in the protocol (based on the first patient). Drug reduction or dose regulation will be implemented according to the research plan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks after initial documentation of response.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is defined as time from date of randomization until the date of first objective progressive disease (PD) by investigator assessment according to RECIST v1.1 or death from any cause, whichever comes first.	24 months
Overall Survival (OS)	OS is defined as the time from randomization until the date of death from any cause.	24 months
Disease control response (DCR)	DCR is defined as the proportion of participants who achieve a complete response (CR), partial response (PR) or or stable disease (SD) .	24 months
Duration of response (DoR)	DoR is defined as the time from the first objective response (CR/PR) to the first documented disease progression (PD) according to RECIST v1.1 or death from any cause, whichever comes first.	24 months
Progression-free survival (PFS) rate of 6 months	2.The 6-month PFS rate is defined as the proportion of patients who are progression-free and alive at 6 months, as assessed by the investigator per RECIST v1.1.	6 months
Progression-free survival (PFS) rate of 1 year	The 1-year PFS rate is defined as the proportion of patients who are progression-free and alive at 1 year, as assessed by the investigator per RECIST v1.1.	1 year
Incidence of Adverse Events	Number of participants with Investigator assessed treatment emergent adverse events per Common terminology criteria for adverse effects (CTCAE) version 5.0	From start of treatment through 60 days after last treatment, approximately 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trop2 expression.	Explore the association of trop2 expression with treatment response and prognosis.	24 months

Collaborators and Investigators

• Sponsor: Sichuan University
• Collaborators: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.; Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jianxin Xue, West China Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 24, 2026
• First Submitted That Met QC Criteria: March 24, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: SCLC; Anlotinib; Trop2-ADC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; anlotinib
• Other Study ID Numbers: HXIRB-2026-323

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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