SBRT, Chemotherapy, and AK112 Neoadjuvant Therapy for Luminal-type Breast Cancer

Official title

A Single-arm, Open, Phase II Clinical Study of SBRT, Chemotherapy, and Ivonescimab Neoadjuvant Therapy for Luminal-type Breast Cancer

Overview

Studies have indicated that the improvement in pathological complete response (pCR) is significantly correlated with luminal breast cancer patients' overall survival (OS). Patients with luminal breast cancer have poor efficacy for neoadjuvant chemotherapy. The combination of neoadjuvant therapy with immunotherapy and chemotherapy has been demonstrated to enhance the pCR rate of luminal-type breast cancer patients, increasing it from 13-15% to approximately 24%. Therefore, how to further improve the pCR rate of luminal-type breast cancer became the main objective of this study. Stereotactic radiotherapy (SBRT) not only kills tumor cells directly, but also kills the distant unirradiated tumor cells by promoting the cross-initiation of tumor-specific CD8+ T cells, a phenomenon known as the abscopal effect. Our research team has recently discovered that the triple therapy model of SBRT + anti-vascular targeting + anti-PD-1 was safe and efficacious in lung cancer patients. Ivonescimab (AK112) is an anti-PD-1/VEGF-A bispecific antibody. In order to improve the pCR, a single-arm, open, phase II clinical study was proposed to explore the safety and efficacy of SBRT+AK112+chemotherapy, a neoadjuvant treatment modality, in the treatment of luminal breast cancer.

Interventions

• Drug Lvonescimab (AK112)
  8Gy×3 SBRT (continuous irradiation) to irradiate the primary lesion (for patients with axillary lymph node metastasis) or 6Gy×3 SBRT (continuous irradiation) to irradiate the primary lesion and axillary lymph node metastasis (for patients without axillary lymph node metastasis) will be administered at first. Then the first cycle of chemotherapy + AK112 will be given within 24 hours after the end of SBRT. The total eight cycles of preoperative chemotherapy combined with immunotherapy will be ad

Primary outcome measures

• Complete pathologic remission (pCR) rate [Time frame: Up to the 30 weeks]

Secondary outcome measures (6)

• Objective response rate (ORR) [Time frame: Up to the 30 weeks]
• Disease control rate (DCR) [Time frame: Up to 30 weeks]
• Residual Cancer Burden (RCB) score [Time frame: At time of surgery]
• Event-free survival (EFS) [Time frame: Up to 12 months after surgery]
• Safety and tolerability [Time frame: Through study completion, an average of 1 year after surgery]
• Quality of life assessment [Time frame: Pretreatment, Pre-operative, and Up to 12 months after surgery]

Eligibility criteria

Inclusion criteria

This trial aims to enroll patients who treatment-naïve and voluntarily participate and provide written informed consent; Eligible participants must have histologically confirmed and HR+/HER2-negative breast cancer (HER2 immunohistochemistry 0, 1+, or 2+/FISH-); Patients must meet at least one of the following criteria: (1) tumor size >2 cm, (2) axillary lymph node metastasis, or (3) intent for breast-conserving surgery, but tumor-to-breast volume ratio makes preservation challenging; Additional eligibility requirements include age ≥18 years, an ECOG performance status of 0-1, and baseline laboratory values within acceptable ranges: white blood cell count (WBC) ≥2.0×10⁹/L, absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count (PLT) ≥100×10⁹/L, hemoglobin (Hb) ≥90 g/L. Liver function parameters must be within ≤1.5×upper limit of normal (ULN) for total bilirubin (TBIL) and ≤3×ULN for alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Renal function must be preserved, with serum creatinine (Cr) ≤1.5× ULN, or if Cr exceeds this limit, the creatinine clearance rate should be ≥50 mL/min (calculated using the Cockcroft-Gault formula). Coagulation parameters should meet the following thresholds: activated partial thromboplastin time (APTT)≤1.5×ULN and prothrombin time (PT) or international normalized ratio (INR) ≤1.5×ULN.

Exclusion criteria

Received chemotherapy, targeted therapy, or radiotherapy within 12 months before the first dose of the investigational drug, or have undergone solid organ or hematologic transplantation; A history of myocardial infarction or uncontrolled arrhythmias (QTc ≥470 ms by Fridericia's formula) within 6 months before the first dose; NYHA class III-IV heart failure, left ventricular ejection fraction (LVEF) <50%, or uncontrolled hypertension (systolic BP ≥150 mmHg and/or diastolic BP ≥100 mmHg); Patients with active HIV, tuberculosis, interstitial lung disease, severe pulmonary impairment, or autoimmune diseases requiring systemic immunosuppression will also be excluded; Participants must not have received a live vaccine within 28 days prior to the first dose, though inactivated influenza vaccines are permitted. Patients requiring systemic corticosteroids (>10 mg/day prednisone equivalent) or immunosuppressants within 14 days before the first dose will be excluded, except for short-term or low-dose corticosteroids, localized applications, and adrenal replacement therapy; Patients with active infections requiring systemic therapy within 14 days prior to enrollment, hepatitis B or C with detectable viral DNA/RNA, history of prior treatment with immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies), participation in another clinical trial within 14 days, major surgery within 4 weeks before the first dose (except for biopsy procedures), severe allergic reactions to monoclonal antibodies or study drug components, pregnancy or lactation, active psychiatric disorders or substance abuse history; Patients who have ceased alcohol consumption may be included. Lastly, investigators may exclude participants based on any other conditions deemed inappropriate for study participation.

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

China · 1 center

• Hubei Cancer Hospital — Wuhan

Publications

• Zhang C, Bi J, Huang Y, Ke Z, Yuan Z, Ruan H, Pi G, Li Y, Shao J, Han G. Neoadjuvant stereotactic body radiotherapy combined with chemotherapy and Ivonescimab for Chinese luminal-type breast cancer patients: study protocol for a single-arm, open-label, phase II trial. BMJ Open. 2025 Sep 10;15(9):e102952. doi: 10.1136/bmjopen-2025-102952. PMID 40935417

Identifiers

NCT: NCT06402435 · HBCH-RT-2024-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗