Given that osteosarcoma typically presents at an early age and predominantly affects pediatric and adolescent populations, early control of disease progression and the opportunity for complete tumor resection are particularly crucial. Postoperatively, patients can regain functional mobility through prosthetic implantation and artificial joint reconstruction, thereby preventing premature loss of mobility in young patients. This study aims to explore the efficacy and safety of neoadjuvant treatment with the PD-L1 antibody envafolimab in combination with standard chemotherapy in patients with resectable stage IIb osteosarcoma, and to assess whether this combined regimen can increase the proportion of patients achieving complete tumor resection.
Patients voluntarily participate in the study and have good compliance, signing a written informed consent form before enrollment.
Age between 12 and 70 years, with no gender restrictions.
Patients diagnosed with non-metastatic, resectable osteosarcoma by pathology and clinical physician assessment.
Have measurable disease (according to RECIST 1.1 criteria, non-nodal lesions with a CT scan longest diameter ≥10 mm, and nodal lesions with a CT scan shortest diameter ≥15 mm).
Participants with a history of or concurrent diagnosis of other malignant tumors (except for cured cutaneous basal cell carcinoma and in situ cervical carcinoma).
Patients with recurrent postoperative or previously treated osteosarcoma with local or systemic anti-tumor therapy, or with metastasis.
Participants who have received the following treatments within 4 weeks prior to study initiation: radiation therapy for tumors, surgical procedures, chemotherapy, immunotherapy, or other investigational drugs.
Known allergies to any component of the study medication in participants. Participants with uncontrolled clinical symptoms or diseases of the heart, such as: (1) NYHA Class II or higher heart failure, (2) unstable angina pectoris, (3) myocardial infarction within the past year, (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
Single group
Envafolimab and neoadjuvant chemotherapy
Drug\* PD-L1 inhibitor envafolimab Paediatric (\<18 years): 2.5 mg/kg (maximum 200 mg) by subcutaneous injection on Day 1 of every week (q1w). Adult (≥18 years): 200 mg flat dose by subcutaneous injection on Day 1 of every week (q1w). * Neoadjuvant chemotherapy--MAP regimen (paediatric patients) Doxorubicin 75 mg/m² intravenously on Days 1-2, administered in weeks 1 and 6 of each 6-week cycle. Cisplatin 120 mg/m² intravenously on Days 1-3, administered in weeks 1 and 6 of each 6-week cycle. Methotrexate 8-12 g/m² intravenously on Day 1 of weeks 3 and 4 of each 6-week cycle. * Neoadjuvant chemotherapy--DIA regimen (adult patients) Doxorubicin 75 mg/m² intravenously on Days 1-2, administered in weeks 1 and 6 of each 6-week cycle. Cisplatin 120 mg/m² intravenously on Days 1-3, administered in weeks 1 and 6 of each 6-week cycle. Ifosfamide 12-15 g/m² total dose intravenously on Days 1-5 of week 3 of each 6-week cycle.
Tumor necrosis rate
According to the Huvos grading system, patient bone tumor specimens were evaluated and analyzed block by block in comparison with preoperative imaging data after sampling, and the data were then summarized. Tumors with necrosis rates of grade I-II were considered to have poor chemotherapeutic response (indicating poor long-term prognosis, and postoperative adjuvant chemotherapy should increase the dose intensity or modify the chemotherapy regimen), while those with necrosis rates of grade III-IV were considered to have a good chemotherapeutic response (it is recommended that postoperative adjuvant chemotherapy use the same chemotherapy regimen as preoperatively). The number of patients in each grade of tumor necrosis rate was counted, and the percentage of patients with tumor cell necrosis rate \>90% (i.e., tumor necrosis rate grade III-IV) among all patients will be used as the primary outcome measure.
EFS (event-free survival)
The time from the start of treatment to the first occurrence of any of the following events: disease progression precluding the possibility of surgical treatment, local or distant recurrence, or death from any cause.
PFS (Progression-free survival)
The time from the start of treatment to disease progression or death of the patient due to any cause.
Immune Microenvironment
The immune microenvironment was assessed by single-cell RNA sequencing (scRNA-seq) of surgically resected specimens. The specific measurement is the relative abundance (percentage) of major immune-cell subsets-CD8+ T cells, CD4+ T cells, regulatory T cells (Treg), natural killer (NK) cells, M1 macrophages, and M2 macrophages-within the total viable tumor-infiltrating leukocytes (CD45+ cells) at the time of surgery. Changes in these cell-type proportions between pre-treatment biopsy and post-treatment surgical samples were computed to evaluate the impact of neoadjuvant immune therapy on the tumor microenvironment.
Adverse Events (AEs)
Adverse Events (AEs) according to CTCAE v5.0
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