A Multicenter, Single-arm, Prospective Phase II Clinical Study of Epalrotokewali Combined With Eribulin, Anlotinib, and Radiotherapy for the Treatment of Patients With Advanced Soft Tissue Sarcoma.

Official title

A Multicenter, Single-arm, Prospective Phase II Clinical Study of Epalrotokewali Monotherapy Combined With Eribulin, Anlotinib, and Radiotherapy for the Treatment of Patients With Advanced Soft Tissue Sarcoma.

Overview

This study intends to enroll patients with advanced soft tissue sarcoma, employing immunotherapy combined with eribulin, anlotinib, and radiotherapy as subsequent-line treatment to preliminarily explore its efficacy and safety. QL1706, a dual-targeting agent against PD-1 and CTLA-4, has been approved by the National Medical Products Administration (NMPA) of China for the second-line treatment of cervical cancer.

Interventions

• Drug QL1706 + Eribulin + Anlotinib + Radiotherapy
  QL1706: 5 mg/kg, intravenous injection (IV) on Day 1, every 3 weeks (Q3W). Eribulin : 1.1 mg/m², intravenous infusion (IV) on Days 1 and 8, Q3W. Anlotinib : Oral administration before breakfast, 12 mg once daily (QD) on Days 1-14, followed by a 1-week drug holiday, Q3W. Radiotherapy : Hypofractionated radiotherapy, 15-60 Gy delivered in 5-8 fractions. Eribulin is administered for 6 cycles. Epalizumab and anlotinib are continued until disease progression, intolerable toxicity, initiation of new

Primary outcome measures

• ORR [Time frame: up to 2 years]

Secondary outcome measures (5)

• DCR [Time frame: up to two years]
• PFS [Time frame: up to two years]
• OS [Time frame: up to two years]
• 6-month PFS rate [Time frame: up to six months]
• DoR [Time frame: up to two years]

Eligibility criteria

Inclusion criteria

• Signed informed consent form;
• Subjects aged 14-75 years;
• Patients with histologically or cytologically confirmed advanced soft tissue sarcoma (STS);
• Patients with STS who have failed first-line or higher treatment;
• At least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1);
• ECOG performance status (PS) score of 0-1;
• Adequate organ and bone marrow function, with laboratory tests meeting the following criteria within 7 days prior to the first dose of study drug (without having received any blood components, hematopoietic growth factors, albumin, or other medications considered corrective therapy by the investigator within 14 days prior to testing):

i. Hematology: Hemoglobin (Hb) ≥90 g/L, absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count (PLT) ≥90×10⁹/L.

ii. Biochemistry: Serum creatinine (Cr) ≤1.5×upper limit of normal (ULN); serum total bilirubin (TBIL) ≤1.5×ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0×ULN for subjects without liver metastases, and ALT and AST ≤5.0×ULN for subjects with liver metastases; serum albumin (ALB) ≥25 g/L.

iii. Coagulation function: International normalized ratio (INR) ≤1.5×ULN; prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN (for subjects receiving prophylactic anticoagulation therapy, the investigator should assess that INR and APTT are within safe and effective therapeutic ranges);

• Women of childbearing potential must use reliable contraception from screening until 3 months after discontinuation of trial medication, and have a negative pregnancy test (serum or urine) within 7 days prior to enrollment. Men must agree to use appropriate contraception or have undergone surgical sterilization from screening until 3 months after discontinuation of trial medication;
• Expected survival time ≥12 weeks.

Exclusion criteria

• History of allergy to QL1706 or any of its components, or contraindication to its treatment;
• Prior administration of QL1706 or eribulin;
• Specific pathological subtypes, such as Ewing sarcoma, non-poly-morphic rhabdomyosarcoma, or gastrointestinal stromal tumor (GIST);
• Resistance or intolerance to anlotinib, eribulin, radiotherapy, or any other contraindications to these treatments;
• Use of any other investigational drug within 4 weeks prior to screening or participation in another clinical trial;
• Diagnosis of immunodeficiency or ongoing systemic corticosteroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first trial treatment;
• Known history of active Mycobacterium tuberculosis (TB) infection;
• Known history of human immunodeficiency virus (HIV) infection;
• Active brain metastases or meningeal metastases;
• Uncontrolled hypertension (systolic blood pressure \[SBP\] ≥140 mmHg or diastolic blood pressure \[DBP\] >90 mmHg despite optimal medical therapy);
• Severe cardiovascular disease: myocardial ischemia of grade II or higher, myocardial infarction, poorly controlled arrhythmia (including QTc interval ≥450 ms in males or ≥470 ms in females); NYHA class III-IV heart failure, or left ventricular ejection fraction (LVEF) <50% as assessed by echocardiography;
• Respiratory syndrome (dyspnea of CTCAE grade ≥2), or uncontrolled serous cavity effusion (including pleural effusion, ascites, or pericardial effusion);
• Active hepatitis C and/or hepatitis B infection (hepatitis B: HBsAg-positive with HBV DNA ≥500 IU/mL; hepatitis C: HCV RNA-positive);
• Major surgical procedure, severe traumatic injury, fracture, or ulcer within 4 weeks prior to randomization;
• History of autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), vascular thrombosis associated with antiphospholipid syndrome (APS), Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome (GBS), multiple sclerosis (MS), vasculitis, or glomerulonephritis;
• Medical history, diseases, treatments, or laboratory abnormalities that may interfere with trial results, prevent the subject from completing the study, or other conditions deemed unsuitable for study participation by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07205185 · RITEA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗