Breast CancerPhase 2NCT06402435
SBRT, Chemotherapy, and AK112 Neoadjuvant Therapy for Luminal-type Breast Cancer
A Phase 2 study testing Lvonescimab (AK112) in people with Breast Cancer, run by Hubei Cancer Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Lvonescimab (AK112)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 28 Nov 2024to 1 Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Hubei Cancer Hospital
Wuhan, Hubei, 430079
Han Guang, MD
Han Guang, MD
About this study
Official title: A Single-arm, Open, Phase II Clinical Study of SBRT, Chemotherapy, and Ivonescimab Neoadjuvant Therapy for Luminal-type Breast Cancer
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.
- Conditions
- Breast Cancer
- Being tested
- Lvonescimab (AK112)
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lvonescimab (AK112)Drug
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 administered.
Surgical resection will be performed within 4-6 weeks after the completion of the eighth cycle.
The chemotherapy regimen consists of: Four cycles of doxorubicin 50 mg/m² (Q3W) + cyclophosphamide 600 mg/m² (Q3W), followed by Four cycles of albumin-bound paclitaxel 125 mg/m², Day 1 and Day 8 (every 28 days).
The immunotherapy drug used is Ivonescimab (AK112) (20mg/kg) , administered every 3 weeks concurrently with chemotherapy for 8 cycles.
| Study group | Role | What they receive |
|---|---|---|
| luminal-type breast cancer patients | Experimental | 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. Receives: Drug: Lvonescimab (AK112) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete pathologic remission (pCR) rate
pCR is defined as ypT0/Tis and ypN0
Measured: Up to the 30 weeks
Secondary outcomes (6)
Objective response rate (ORR)
Percentage of participants achieving complete response (CR) or partial response (PR), assessed by RECIST v1.1 and iRECIST.
Measured: Up to the 30 weeks
Disease control rate (DCR)
Percentage of participants achieving CR, PR, or stable disease (SD), assessed by RECIST v1.1 and iRECIST.
Measured: Up to 30 weeks
Residual Cancer Burden (RCB) score
Quantitative pathological assessment of residual disease in breast and lymph nodes.
Measured: At time of surgery
Event-free survival (EFS)
Time from enrollment to disease progression, recurrence, or death.
Measured: Up to 12 months after surgery
Safety and tolerability
Incidence and severity of adverse events graded by CTCAE v5.0.
Measured: Through study completion, an average of 1 year after surgery
Quality of life assessment
Measured using the EORTC QLQ-BR23 and QLQ-C30 questionnaires.
Measured: Pretreatment, Pre-operative, and Up to 12 months after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2024
- Study start28 Nov 2024
- Primary completion31 Aug 2026 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hubei Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, HAN GUANG, Hubei Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06402435
- Sponsor's protocol ID
- HBCH-RT-2024-01
- Status last verified
- Jun 2025
- First submitted
- 27 Apr 2024
- Last updated
- 2 Jul 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) that support the results reported in the publication, including data presented in text, tables, figures, and appendices.
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.
PubMed 40935417
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Open, Phase II Clinical Study of SBRT, Chemotherapy, and Ivonescimab Neoadjuvant Therapy for Luminal-type Breast Cancer
- ClinicalTrials.gov ID
- NCT06402435
- Acronym / sponsor ID
- HBCH-RT-2024-01
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Hubei Cancer HospitalUniversity, hospital or other
- Study start
- 28 Nov 2024 (actual)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 7 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| luminal-type breast cancer patients | Experimental | Drug: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 administered. Surgical resection will be performed within 4-6 weeks after the completion of the eighth cycle. The chemotherapy regimen consists of: Four cycles of doxorubicin 50 mg/m² (Q3W) + cyclophosphamide 600 mg/m² (Q3W), followed by Four cycles of albumin-bound paclitaxel 125 mg/m², Day 1 and Day 8 (every 28 days). The immunotherapy drug used is Ivonescimab (AK112) (20mg/kg) , administered every 3 weeks concurrently with chemotherapy for 8 cycles. | Drug | luminal-type breast cancer patients |
Primary outcome
Complete pathologic remission (pCR) rate
Time frame: Up to the 30 weeks
pCR is defined as ypT0/Tis and ypN0
6 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2025.
- Derived from this study: PubMed 40935417Zhang 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.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) that support the results reported in the publication, including data presented in text, tables, figures, and appendices.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lvonescimab (AK112) in people with Breast Cancer, run by Hubei Cancer Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xinjun Liang (13995607152, hbchgcp_003@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete pathologic remission (pCR) rate (time frame: Up to the 30 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06402435, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2025.