A Phase 2 interventional study of Iparomlimab and Tuvonralimab (QL1706) and Aromatase Inhibitor (AI) in Breast Cancer, sponsored by Hebei Medical University Fourth Hospital. Not yet recruiting. Open to female participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-08-26.
Sponsored by Hebei Medical University Fourth Hospital · Phase 2, Interventional, and Treatment
This study will evaluate whether adding QL1706 (iparomlimab and tuvonralimab) to neoadjuvant endocrine therapy improves tumor response in patients with hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer who have had a poor response to neoadjuvant chemotherapy.
Approximately 40 participants whose tumors have decreased by less than 40% on magnetic resonance imaging after two cycles of neoadjuvant TAC chemotherapy will be randomly assigned in a 1:1 ratio to receive either an aromatase inhibitor plus a CDK4/6 inhibitor or the same treatment combined with QL1706. Premenopausal and perimenopausal participants will also receive ovarian function suppression.
The main outcome is the objective response rate during the study treatment period. Pathological response, changes in Ki-67, treatment safety, and changes in the tumor immune microenvironment will also be evaluated.
Patients with HR-positive/HER2-negative breast cancer may have an inadequate response to neoadjuvant chemotherapy, and an optimal subsequent neoadjuvant treatment strategy for this population has not been established. QL1706 is a bifunctional combination antibody consisting of iparomlimab, which targets programmed cell death protein 1 (PD-1), and tuvonralimab, which targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Simultaneous inhibition of these immune checkpoints may enhance antitumor immune activity. This study will explore whether the addition of QL1706 to endocrine therapy and CDK4/6 inhibition improves tumor response in patients who have had a poor early response to neoadjuvant chemotherapy.
This is an exploratory, open-label, prospective, randomized controlled study. Approximately 40 women with stage IIB-IIIC HR-positive/HER2-negative early or locally advanced breast cancer will be enrolled. Eligible participants must have received two cycles of neoadjuvant TAC chemotherapy and have a reduction in tumor size of less than 40% on magnetic resonance imaging. Participants will be randomly assigned in a 1:1 ratio to the experimental arm or the active comparator arm.
Participants in the active comparator arm will receive an aromatase inhibitor plus a CDK4/6 inhibitor. Participants in the experimental arm will receive the same treatment combined with QL1706 at 5 mg/kg by intravenous infusion on Day 1 of each 3-week cycle for six cycles. Premenopausal and perimenopausal participants will receive ovarian function suppression. Surgery will be performed after completion of neoadjuvant treatment based on clinical assessment.
The primary outcome is the objective response rate according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary outcomes include breast pathological complete response, total pathological complete response, Miller-Payne grade, residual cancer burden class, changes in Ki-67 expression, and the incidence of immune-related and other adverse events. Exploratory analyses will assess changes in the tumor immune microenvironment, including immune-cell infiltration and the expression of PD-1, programmed death-ligand 1, and CTLA-4, using blood and tumor specimens collected at protocol-specified time points.
14,825 studies on the registry are indexed under Breast Neoplasms; 3,319 are open to participants now.
This study's planned enrollment of 40 is below the median of 72 across 10,896 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Hebei Medical University Fourth Hospital is the lead sponsor of 81 studies on the registry; 54 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive an aromatase inhibitor plus a CDK4/6 inhibitor and QL1706. QL1706 will be administered intravenously at 5 mg/kg on Day 1 of each 3-week cycle for six cycles. The aromatase inhibitor and CDK4/6 inhibitor will be administered according to their respective prescribing information or applicable clinical guidelines throughout the neoadjuvant treatment period. Premenopausal and perimenopausal participants will also receive ovarian function suppression.
Drug: Iparomlimab and Tuvonralimab (QL1706) · Drug: Aromatase Inhibitor (AI) · Drug: CDK4/6 inhibitor · Drug: Ovarian function suppression
Participants will receive an aromatase inhibitor plus a CDK4/6 inhibitor according to the respective prescribing information or applicable clinical guidelines throughout the neoadjuvant treatment period. Premenopausal and perimenopausal participants will also receive ovarian function suppression.
Drug: Aromatase Inhibitor (AI) · Drug: CDK4/6 inhibitor · Drug: Ovarian function suppression
Drug page: Iparomlimab/Tuvonralimab
Iparomlimab and tuvonralimab (QL1706) will be administered intravenously at 5 mg/kg on Day 1 of each 3-week cycle for six cycles.
Participants will receive exemestane, anastrozole, or letrozole. The specific aromatase inhibitor, dose, and administration schedule will be selected according to the applicable prescribing information or clinical guidelines and will be continued throughout the approximately 18-week neoadjuvant treatment period.
Also known as: Exemestane, Anastrozole, Letrozole
Drug page: Abemaciclib
Participants will receive abemaciclib or ribociclib. The specific CDK4/6 inhibitor, dose, and administration schedule will be selected according to the applicable prescribing information or clinical guidelines and will be continued throughout the approximately 18-week neoadjuvant treatment period.
Also known as: Abemaciclib, Ribociclib
Premenopausal and perimenopausal participants will receive ovarian function suppression with goserelin, leuprorelin, or triptorelin. The specific agent, dose, and administration schedule will follow the applicable prescribing information or clinical guidelines.
Also known as: Goserelin, Leuprorelin, Triptorelin
This study also gives Ribociclib, Anastrozole, Exemestane. No intervention listed here names it: that was found by reading the record.
Objective Response Rate (ORR)
The proportion of participants whose best overall response is complete response (CR) or partial response (PR), as assessed by computed tomography or magnetic resonance imaging according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR will be calculated as the number of participants achieving CR or PR divided by the total number of participants included in the efficacy analysis, multiplied by 100%.
Time frame: From randomization through the preoperative assessment after six treatment cycles, approximately 18 weeks
Breast Pathological Complete Response Rate (bpCR)
Time frame: At surgery after completion of six treatment cycles, approximately 18 weeks after randomization
Total Pathological Complete Response Rate (tpCR)
Time frame: At surgery after completion of six treatment cycles, approximately 18 weeks after randomization
Miller-Payne Grade
Pathological response of the primary breast tumor will be assessed using the Miller-Payne grading system, which ranges from Grade 1 to Grade 5. Grade 1 indicates no or minimal reduction in tumor cells, whereas Grade 5 indicates no identifiable malignant cells at the primary tumor site. A higher grade indicates a better pathological response to treatment.
Time frame: At surgery after completion of six treatment cycles, approximately 18 weeks after randomization
Residual Cancer Burden (RCB) Class
Residual cancer burden will be assessed in the resected breast and regional lymph nodes and classified as RCB-0, RCB-I, RCB-II, or RCB-III. RCB-0 indicates no residual invasive cancer, whereas RCB-III indicates extensive residual disease. A higher RCB class indicates a greater residual tumor burden and a worse pathological response to treatment.
Time frame: At surgery after completion of six treatment cycles, approximately 18 weeks after randomization
Incidence of Immune-Related Adverse Events
Time frame: From the first dose of study treatment through 30 days after the last dose, approximately 22 weeks
Change From Baseline in Ki-67 Expression
Ki-67 expression will be assessed by immunohistochemistry in tumor tissue obtained at baseline and at surgery and reported as the percentage of positively stained tumor cells (range, 0% to 100%). Change from baseline will be calculated as the value at surgery minus the baseline value and reported in percentage points (possible range, -100 to 100). A negative value indicates a reduction in Ki-67 expression, with a more negative value indicating greater suppression of tumor cell proliferation.
Time frame: From baseline to surgery after completion of six treatment cycles, approximately 18 weeks
Change in Tumor Immune-Cell Infiltration
Time frame: From baseline to surgery after completion of six treatment cycles, approximately 18 weeks
Change in PD-1 Expression
Time frame: From baseline to surgery after completion of six treatment cycles, approximately 18 weeks
Change in PD-L1 Expression
Time frame: From baseline to surgery after completion of six treatment cycles, approximately 18 weeks
Change in CTLA-4 Expression
Time frame: From baseline to surgery after completion of six treatment cycles, approximately 18 weeks
Change in ESTIMATE Score
The ESTIMATE score will be calculated from tumor gene-expression data using the ESTIMATE algorithm at baseline and at surgery. The ESTIMATE score is a continuous, data-dependent measure without fixed minimum or maximum values. A higher score indicates a greater overall proportion of immune and stromal components and lower estimated tumor purity; a positive change indicates an increase in these non-tumor components after treatment.
Time frame: From baseline to surgery after completion of six treatment cycles, approximately 18 weeks
No study locations are listed for this record.
Plan to share: No — Individual participant data will not be shared because the data contain confidential clinical and biomarker information and are subject to participant privacy, informed consent, and ethics requirements. Aggregated study results will be reported through the ClinicalTrials.gov registry and scientific publications.
No publications or documents are linked to this record.
Start is estimated for Oct 2026; primary completion for Jun 2028, 20 months later.
Of 1,070 non-industry phase 2 interventional studies under Breast Neoplasms, half reached primary completion within 56 months of starting (the median), counting those still running; a quarter within 34 and three quarters within 87. This study's planned 20 months is below that.
Counting every sponsor, half of 1,302 studies reached it within 51 months; a quarter within 30 and three quarters within 82.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Iparomlimab/Tuvonralimab
Hebei Medical University Fourth Hospital