A Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of Sacituzumab Tirumotecan in Second-Line and Subsequent Treatments for Advanced Thymic Epithelial Tumors

A Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of Sacituzumab Tirumotecan in Second-Line and Subsequent Treatments for Advanced Thymic Epithelial Tumors

This is a single-arm, phase II study to evaluate the efficacy and safety of Sacituzumab Tirumotecan, a TROP2-directed antibody-drug conjugate, in patients with advanced thymic epithelial tumors who have received second-line or later therapy.

This study aims to evaluate the efficacy and safety of Sacituzumab Tirumotecan, a TROP2-directed antibody-drug conjugate, in patients with advanced thymic epithelial tumors who have received second-line or later therapy. The study is designed as a prospective, single-arm, phase II clinical trial. Eligible patients must meet the inclusion/exclusion criteria, have received prior systemic therapy, and have a pathological diagnosis of advanced thymic epithelial tumor. Enrolled patients will receive Sacituzumab Tirumotecan at a dose of 5 mg/kg via intravenous infusion. Treatment cycles repeat every 4 weeks, with administration on Day 1 and Day 15 of each cycle. Treatment will continue until disease progression (as defined by loss of clinical benefit), intolerable toxicity, patient withdrawal, or meeting other protocol-specified discontinuation criteria. The primary endpoint of this study is the Objective Response Rate (ORR), defined as the proportion of patients achieving a confirmed Complete Response (CR) or Partial Response (PR) as their best overall response, assessed according to RECIST version 1.1. Secondary endpoints include Progression-Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DOR), Overall Survival (OS), incidence of Adverse Events (AEs), and Quality of Life (QoL) assessments. Following treatment discontinuation, subjects will enter a follow-up phase consisting of safety follow-up and survival follow-up, with survival status assessed every 90 days.

Inclusion Criteria:

1. Advanced (unresectable or metastatic) thymic epithelial tumor confirmed by histology or cytology.
2. Progress after receiving at least first-line systemic therapy (chemotherapy or immune checkpoint inhibitor).
3. According to RECISTv1.1 standard, there is at least one measurable lesion.
4. No central nervous system metastasis or stable brain metastasis after treatment (asymptomatic and hormone withdrawal for ≥4 weeks).
5. Age > 18 years old, male or female.
6. ECOG (Performance status, PS) score 0-1.
7. Expected survival time ≥12 weeks.
8. Organ function compliance (confirmed by laboratory examination within 14 days before treatment): Bone marrow function: I. Neutrophils ≥ 1500× 109/L; Ii. Platelets ≥ 100× 109/L; Iii. hemoglobin > 90g/l; Renal function: I. Serum creatinine ≤1.5×ULN or creatinine clearance rate (CrCl). ≥50mL/min； Ii. Urine protein < 2+or 24H urine protein quantitative < <1.0g；; Liver function: I, AST or ALT ≤ 3× ULN; For patients with liver metastasis, it can ≤5*ULN； Ii. Total bilirubin ≤1.5×ULN, and liver metastasis patients ≤ 3× ULN; Iii: serum albumin (ALB) ≥ 28g/l; Coagulation function: NR or APTT≤1.5×ULN；; Cardiac function: Left ejection fraction (LEFF) ≥ 50%.
9. Before making any evaluation related to the study, the subjects must understand and volunteer. Sign the informed consent form and voluntarily comply with other requirements of the study.
10. Female subjects with reproductive function must be treated within 3 days before the first medication. Urine or serum pregnancy test (if the result of urine pregnancy test cannot be confirmed as negative, serum pregnancy test is needed, and the serum pregnancy result shall prevail). If a fertile woman has sex with an unsterilized male partner, the subjects agree to continue using contraception and avoid breastfeeding during the medication.
11. Male subjects are willing to agree to continue using contraception during the medication.

Exclusion Criteria:

1. Previously received targeted drug therapy with Lucasatuzumab.
2. Have received any drug therapy targeting topoisomerase I in the past, including antibody-coupled drug (ADC) therapy.
3. Patients with grade 3-4 interstitial lung disease.
4. Subjects known to have meningeal metastasis, brain stem metastasis, spinal cord metastasis and/or compression, active or brain metastasis without local treatment. 5.Subjects with brain metastases who have previously received local treatment can participate in the study if they are clinically stable for at least 4 weeks before the first administration of the study treatment and do not need to use corticosteroids or anticonvulsants for at least 14 days before the first administration; For the subjects with brain metastases first discovered during screening, if they receive local treatment (such as radiotherapy), they must have imaging evidence to show that the brain metastases have not progressed for at least 4 weeks from the first imaging diagnosis of brain metastases, and they can only enter the group after confirming that the brain metastases are stable.
5. Patients with previous malignant tumors (except skin malignant tumors other than melanoma, and carcinoma in situ in the following parts [bladder, stomach, colorectal cancer, endometrium, cervix, melanoma or breast]) cannot be included in this study. However, if the malignant tumor has achieved complete remission for five years or more, and no additional anti-tumor treatment is needed during this study, it can be included in the study.
6. Myocardial infarction and uncontrolled arrhythmia occurred within 6 months before the first administration (including QTc interval ≥450ms for men and ≥ 470 ms for women) (QTc interval is calculated by Fridericia formula); Or grade III-IV cardiac insufficiency according to NYHA standard or left ventricular ejection fraction < 50% by color Doppler echocardiography.
7. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage. Only a small amount of pleural effusion, a small amount of ascites and a small amount of pericardial effusion without clinical symptoms shown by imaging can be included in the group.
8. Subjects with active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, abdominal abscess or acute gastrointestinal bleeding.
9. Patients with active hepatitis B, hepatitis C, tuberculosis and syphilis or other serious infections with poor clinical control.
10. HIV positive or diagnosed with acquired immunodeficiency disease (AIDS).
11. Known allergic to the study drug or any of its components (including polysorbate -20), known history of severe hypersensitivity to other monoclonal antibodies (NCI-CTCAE5.0 grade is greater than grade 3).
12. Before the first administration, he was receiving long-term systemic corticosteroid therapy of > 10mg of prednisone or equivalent dose of systemic corticosteroid therapy or equivalent anti-inflammatory active drugs or any form of immunosuppressive therapy. Subjects who need bronchodilators, inhaled or topical steroids or local steroid injections, and who are used as preventive drugs for hypersensitivity (such as drugs before CT examination) may be admitted into the group.
13. Known history of hereditary bleeding tendency disease or coagulation dysfunction.
14. Pregnant or lactating women.
15. During the screening before the first administration, the condition deteriorated rapidly, such as serious changes in physical state.
16. The researcher thinks that the patient can't finish the study medically, psychologically or physically or can't understand the information in the patient manual.
17. Those who have been vaccinated with live or attenuated vaccines within 28 days before the first administration or have plans to vaccinate such vaccines during the study period; However, inactivated virus vaccines for seasonal influenza are allowed to be used.