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

Phase 2

Recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Lvonescimab (AK112)

• Registration Number: NCT06402435
• Lead Sponsor: Hubei Cancer Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-27
• Study First Submitted QC: 2024-05-02
• Study First Posted: 2024-05-07
• Study Start: 2024-11-28
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-27
• Last Update Posted: 2025-07-02
• Primary Completion: 2026-08-31
• Study Completion: 2027-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 50

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
luminal-type breast cancer patients	Lvonescimab (AK112)	The study included patients with a histologically confirmed of HR+/HER2-negative (Her2 immunohistochemistry of 0, 1+, or 2+/FISH-) breast cancer who met one of the following criteria: (1) primary tumor mass larger than 2 cm, (2) axillary lymph node metastasis, (3) a willingness to conserve the breasts, but where the ratio of the tumor size to the volume of the breast was large enough to make it difficult to conserve the breasts.
luminal-type breast cancer patients	Lvonescimab (AK112)	The study included patients with a histologically confirmed of HR+/HER2-negative (Her2 immunohistochemistry of 0, 1+, or 2+/FISH-) breast cancer who met one of the following criteria: (1) primary tumor mass larger than 2 cm, (2) axillary lymph node metastasis, (3) a willingness to conserve the breasts, but where the ratio of the tumor size to the volume of the breast was large enough to make it difficult to conserve the breasts.

Primary Outcome Measures

Name	Time	Method
Complete pathologic remission (pCR) rate	Up to the 30 weeks	pCR is defined as ypT0/Tis and ypN0

Secondary Outcome Measures

Name	Time	Method
Event-free survival (EFS)	Up to 12 months after surgery	Time from enrollment to disease progression, recurrence, or death.
Disease control rate (DCR)	Up to 30 weeks	Percentage of participants achieving CR, PR, or stable disease (SD), assessed by RECIST v1.1 and iRECIST.
Safety and tolerability	Through study completion, an average of 1 year after surgery	Incidence and severity of adverse events graded by CTCAE v5.0.
Objective response rate (ORR)	Up to the 30 weeks	Percentage of participants achieving complete response (CR) or partial response (PR), assessed by RECIST v1.1 and iRECIST.
Residual Cancer Burden (RCB) score	At time of surgery	Quantitative pathological assessment of residual disease in breast and lymph nodes.
Quality of life assessment	Pretreatment, Pre-operative, and Up to 12 months after surgery	Measured using the EORTC QLQ-BR23 and QLQ-C30 questionnaires.

Trial Locations

Locations (1)

Hubei Cancer Hospital; 🇨🇳 Wuhan, Hubei, China