Clinical Trials of Benmelstobart Injection Combined With Anlotinib Hydrochloride Capsules in the Treatment of Advanced or Unresectable Alveolar Soft Part Sarcoma

To Evaluate the Single-arm, Multi-center Phase II Clinical Trial of Benmelstobart Injection Combined With Anlotinib Hydrochloride Capsules in the Treatment of Advanced or Unresectable Alveolar Soft Part Sarcoma

This is a Phase II, single-arm, multicenter clinical study aimed at demonstrating the effectiveness of benmelstobart injection combined with anlotinib hydrochloride capsules in patients aged 14 years or older with advanced or unresectable alveolar soft part sarcoma by evaluating the objective response rate (IRC).

Inclusion Criteria:

• Only when all the following criteria are met will the subjects be eligible for inclusion in this study:

  1. The subjects voluntarily join this study, sign the informed consent form, and have good compliance;

  2. ≥14 years old (calculated from the date of signing the informed consent form);

  3. Eastern Cooperative Oncology Group Performance Status (ECOG) score of 0 to 1;

  4. Expected survival greater than 12 weeks;

  5. Pathologically confirmed recurrent and/or metastatic or unresectable alveolar soft part sarcoma, without previous systemic treatment;

  6. Confirmed to have at least one measurable lesion according to RECIST 1.1;

  7. Laboratory tests meet the following standards:

     1. Hemoglobin (HGB) ≥ 90g/L;
     2. Absolute neutrophil count (NEUT) ≥ 1.5×109/L;
     3. Platelet count (PLT) ≥ 100×109/L.
     4. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN);
     5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 ULN. If there is liver metastasis, ALT and AST ≤ 5 ULN;
     6. Serum creatinine (CR) ≤ 1.5 ULN or creatinine clearance rate (CCR) ≥ 60ml/min;
     7. Prothrombin time (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR) ≤ 1.5×ULN (if not receiving anticoagulant therapy);
     8. Thyroid stimulating hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels should be examined. If T3 and T4 levels are normal, the subject can be included.

  8. Women of childbearing age must agree to use effective contraceptive measures during the study and for 6 months after the study, and have a negative serum test within 7 days before study enrollment; men must agree to use effective contraceptive measures during the study and for 6 months after the study.

Exclusion Criteria:

• Any subject meeting any of the following criteria will be excluded from this trial:

  1. Having had or currently having another malignant tumor within 5 years before the first administration of the drug. The following two situations are eligible for inclusion: other malignant tumors treated with a single surgery and achieving a disease-free survival (DFS) of at least 5 consecutive years; cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading the basement membrane)].

  2. Having diseases that affect intravenous injection or blood collection, or having multiple factors that affect oral medication (such as inability to swallow, chronic diarrhea, and intestinal obstruction, etc.).

  3. Adverse reactions from previous treatments have not recovered to a Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade score of ≤1, except for grade 2 alopecia, grade 2 peripheral neuropathy, grade 2 anemia, non-clinically significant and asymptomatic laboratory abnormalities, and stable hypothyroidism treated with hormone replacement therapy, which are judged by the investigator to have no safety risks.

  4. Having undergone major surgery, significant traumatic injury, or expected to undergo major surgery during the study period within 4 weeks before the first administration of the drug (except for surgeries specified in the protocol), or having long-term unhealed wounds or fractures. (Major surgery is defined as: surgeries classified as grade 3 or above in the 2023 version of the surgical classification directory of the participating center).

  5. Having experienced any bleeding or hemorrhagic event ≥ CTCAE grade 3 within 4 weeks before the first administration of the drug.

  6. Having experienced an arterial or venous thrombotic event within 6 months before the first administration of the drug, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, and pulmonary embolism.

  7. Active viral hepatitis that is not well controlled. Subjects meeting the following requirements can be screened: HBsAg-positive subjects must have Hepatitis B Virus (HBV) DNA quantification < 2000 IU/ml (or 1*104 copies/ml) or have received at least 1 week of antiviral treatment for HBV before the start of the study and have a 10-fold (1 log value) or greater reduction in viral index, and be willing to receive antiviral treatment throughout the study; HCV-infected subjects (HCV Ab or HCV RNA positive): judged by the investigator to be in a stable state or receiving antiviral treatment at the time of enrollment and continuing to receive approved antiviral treatment during the study.

  8. Active syphilis infection requiring treatment.

  9. Having active tuberculosis, a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia, radiation pneumonitis requiring treatment, or active pneumonia with clinical symptoms.

  10. Having a history of substance abuse of psychotropic drugs and being unable to quit or having a mental disorder.

  11. Preparing for or having previously received allogeneic bone marrow transplantation or solid organ transplantation.

  12. Having major cardiovascular diseases, including any of the following conditions:

      1. Cardiac insufficiency of New York Heart Association Functional Classification (NYHA) class II or above or echocardiography showing left ventricular ejection fraction (LVEF) < 50%;
      2. History of clinically significant ventricular arrhythmias (such as sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes ventricular tachycardia) or arrhythmias requiring continuous antiarrhythmic drug treatment;
      3. Unstable angina pectoris;
      4. Myocardial infarction within 12 months;
      5. Fridericia-corrected QT interval (QTcF) > 450 milliseconds (msec) for men and > 470 msec for women (if QTc is abnormal, it can be continuously measured three times with an interval of more than 2 minutes, and the average value is taken);
      6. History or family history of congenital long QT syndrome. 7) A history of deep vein thrombosis, pulmonary embolism or any other serious thromboembolic event within 3 months prior to randomization (implantable venous access ports or catheter-related thrombosis, or superficial venous thrombosis are not considered "serious" thromboembolic events);
      7. Currently using or having used within 7 days prior to the start of study treatment aspirin (>325 mg/day (maximum antiplatelet dose)), dipyridamole, ticlopidine, clopidogrel, or cilostazol;

  13. Active or uncontrolled severe infection (≥CTC AE grade 2 infection);

  14. Renal failure requiring hemodialysis or peritoneal dialysis;

  15. History of immunodeficiency, including HIV positivity or other acquired or congenital immunodeficiency diseases;

  16. Subjects who need to use immunosuppressants, systemic or absorbable local hormones for immunosuppression purposes and will continue to do so within 7 days before the first administration (except for glucocorticoids at a daily dose of <10 mg prednisone or other equivalent efficacy hormones);

  17. Patients with epilepsy requiring treatment;

  18. Tumor-related symptoms and treatment:

      1. Having received treatment with traditional Chinese patent medicines with clear anti-tumor indications in the National Medical Products Administration (NMPA)-approved drug instructions (including Compound Cantharidin Capsules, Kang'ai Injection, Kanglaite Capsules/Injection, Aidi Injection, Brucea javanica Oil Injection/Capsules, Xiaoaiping Tablets/Injection, Chan Su Capsules, etc.) within 2 weeks prior to the start of study treatment;
      2. Having received previous treatment with immune checkpoint inhibitors targeting PD-1, PD-L1, or Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4);
      3. Having previously used anti-angiogenic drugs such as bevacizumab, anlotinib, apatinib, lenvatinib, sorafenib, sunitinib, regorafenib, or fruquintinib;
      4. Having received treatment with drugs with immunomodulatory functions (such as interleukin-2, thymosin, polysaccharides from Lentinus edodes, etc.) within 30 days prior to the start of treatment;
      5. Not having recovered from the toxicity and/or complications of previous interventions to CTCAE ≤ grade 1, except for alopecia and peripheral neuropathy ≤ grade 2. ；
      6. Imaging studies (CT or MRI) show that the tumor has invaded major blood vessels or the investigator deems that the tumor is highly likely to invade major blood vessels and cause fatal hemorrhage during the subsequent study period;
      7. Uncontrolled pleural effusion, pericardial effusion or moderate to severe ascites (as judged by the investigator) that requires repeated drainage;
      8. Known to have spinal cord compression, carcinomatous meningitis, brain metastases with symptoms or symptoms controlled for less than 4 weeks.

  19. Known to be allergic to the excipients of the study drug.

  20. Participants who have taken part in and used other anti-tumor clinical trial drugs within 4 weeks before the first administration of the study drug.

  21. As judged by the investigator, there are serious conditions that endanger the safety of the participant or affect the participant's completion of the study.