QL1706 Plus Chemotherapy as Neoadjuvant Therapy in Early High-Risk ER+/HER2- Breast Cancer

NCT06404463 | Not Yet Recruiting Phase 2

• 1 other identifier: SCHBCC-N070
• Study Type: interventional
• Target: 76
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will look at the efficacy and safety of QL1706 plus albumin-bound paclitaxel followed by AC/EC in a neoadjuvant setting, in high-risk, ER+/HER2- early breast cancer.

Conditions

Early Breast Cancer; Neoadjuvant Therapy; HR+HER2- Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Total Pathological complete response (tpCR) rate using the definition of ypT0/Tis ypN0

  No invasive residual in breast or nodes; noninvasive breast residuals allowed ) at the time of definitive surgery

  Up to approximately 36 weeks after study start

Secondary Outcomes (4)

• pCR rate using an alternative definition, ypT0/Tis

  Up to approximately 36 weeks after study start

• pCR rate in PD-L1+ population

  Up to approximately 36 weeks after study start

• rate of RCB scored 0-1

  Up to approximately 36 weeks after study start

• Objective Response Rate (ORR) Objective Response Rate (ORR) Objective Response Rate (ORR) Objective Response Rate (ORR)Objective Response Rate (ORR)

  Up to approximately 36 weeks after study start

Study Arms (1)

QL1706

EXPERIMENTAL

QL1706 (bispecific antibody (bsAb) targeting PD-1 and CLTA-4)+nab-P-AC/EC

Drug: QL1706 (bispecific antibody targeting PD-1 and CLTA-4); Drug: Albumin-bound paclitaxel; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Epirubicin

Interventions

QL1706 (bispecific antibody targeting PD-1 and CLTA-4) DRUG

QL1706 is a novel bispecific combination antibody composed of a recombinant humanized IgG4 monoclonal antibody targeting human PD-1 (programmed cell death protein 1) (PSB103) and a recombinant humanized IgG1 monoclonal antibody targeting human CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) (PSB105). Both antibodies have undergone engineering modifications to introduce mutations facilitating their correct assembly and preventing mispairing, and are expressed in the same cell line at a predetermined ratio (approximately 2:1).

QL1706

Albumin-bound paclitaxel DRUG

Albumin-bound paclitaxel improves the solubility and delivery of paclitaxel to tumor cells by binding to human albumin, facilitating its transportation through the bloodstream and enhancing its uptake into tumor tissue. It works by binding to and stabilizing microtubules within cancer cells, thereby disrupting the normal process of cell division and leading to cell cycle arrest and apoptosis, ultimately resulting in the death of cancer cells.

QL1706

Doxorubicin DRUG

Doxorubicin, a widely used chemotherapy drug, belongs to the anthracycline class and is effective against various cancers, including breast cancer, leukemia, and sarcomas. It works by intercalating with DNA and inhibiting topoisomerase II, leading to DNA damage and disruption of DNA replication and transcription processes within cancer cells. Despite its efficacy, doxorubicin may cause side effects such as cardiotoxicity and bone marrow suppression, limiting its long-term use in some patients.

QL1706

Cyclophosphamide DRUG

Cyclophosphamide is a chemotherapy medication commonly used to treat various types of cancers, including lymphoma, leukemia, and breast cancer. It belongs to the class of alkylating agents and works by crosslinking DNA strands, which prevents cell division and leads to cell death. While effective in treating cancer, cyclophosphamide can also cause side effects such as nausea, vomiting, and suppression of the immune system.

QL1706

Epirubicin DRUG

Epirubicin, a chemotherapy medication, is part of the anthracycline class and is used in the treatment of various cancers, including breast cancer, ovarian cancer, and soft tissue sarcoma. It functions by interfering with DNA replication and RNA synthesis within cancer cells, ultimately leading to cell death. Despite its efficacy, epirubicin can cause side effects such as nausea, hair loss, and bone marrow suppression.

QL1706

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily join this study and sign the informed consent form;
• Female patients aged ≥18 years and ≤70 years old who are newly diagnosed with breast cancer. According to the definition of the latest ASCO/CAP guidelines, histopathologically confirmed ER+/HER2- breast cancer, histological grade II, Ki-67 ≥ 20% and TNM stage T1c-T2, cN1-cN2 or T3- T4, cN0-cN2;
• According to RECIST 1.1, there is at least one measurable lesion;
• ECOG score: 0\~1;
• Tumor tissue specimens that can be used for biomarker detection;
• The function of vital organs meets the following requirements (no blood components or cell growth factor drugs are allowed within 14 days before the first medication):
• (1) Absolute neutrophil count ≥1.5×109/L; (2) Platelets ≥100×109/L; (3) Hemoglobin ≥90 g/L; (4) Serum albumin ≥30 g/L; (5) Thyroid-stimulating hormone (TSH) ≤1×ULN (if abnormal, the FT3 and FT4 levels should be examined at the same time. If the FT3 and FT4 levels are normal, you can be included in the group); (6) Serum total bilirubin ≤1.5×ULN; (7) ALT and AST ≤2.5×ULN, if liver metastasis is present, ALT and AST ≤5ULN; (8) AKP≤2.5×ULN; Serum creatinine ≤1.5×ULN; (9) International normalized ratio (INR) ≤1.5 (not receiving anticoagulant therapy).

You may not qualify if:

• The presence of any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism; Those who suffer from vitiligo or whose asthma has been completely relieved in childhood and do not need any intervention in adulthood can be included; asthma that requires medical intervention with bronchodilators cannot be included);
• Are currently using immunosuppressants or systemic hormone therapy to achieve immunosuppression (dose \>10 mg/day prednisone or other effective hormones), and are still using it within 2 weeks before enrollment;
• Severe allergic reactions to other monoclonal antibodies;
• Known history or evidence of interstitial lung disease or active non-infectious pneumonia;
• Those with known central nervous system metastasis;
• Suffered from other malignant tumors in the past 5 years or at the same time (except cured basal cell carcinoma of the skin and cervical cancer in situ);
• Suffering from high blood pressure that cannot be well controlled by antihypertensive drug treatment (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg); the above parameters are allowed to be achieved through the use of antihypertensive treatment; there has been a hypertensive crisis or high blood pressure in the past Hypertensive encephalopathy;
• Have cardiac clinical symptoms or diseases that cannot be well controlled, such as (1) NYHA grade 2 or above heart failure (2) Unstable angina (3) Myocardial infarction within 1 year (4) Clinically significant supraventricular infarction or ventricular arrhythmia requiring treatment or intervention (5) QTc\>450ms (male); QTc\>470ms (female);
• Those who are receiving thrombolysis or anticoagulation therapy are allowed to use low-dose aspirin and low-molecular-weight heparin prophylactically;
• Have clinically significant bleeding symptoms or a clear bleeding tendency within 3 months before enrollment; if fecal occult blood is positive during the baseline period, it can be re-examined. If it is still positive after the reexamination, a gastroscopy is required;
• The tumor invades important blood vessels, or the researcher determines based on imaging that there is a high possibility that the cancer will invade important blood vessels in the future study period, which may lead to fatal bleeding;
• Patients with pleural effusion, ascites or pericardial effusion that require drainage can be enrolled if the researcher assesses that the symptoms are stable after drainage;
• Arterial/venous thrombosis events that occurred within 6 months before enrollment, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
• Known hereditary or acquired bleeding and thrombotic tendencies (such as hemophilia patients, coagulation disorders, etc.);
• Major vascular disease (for example, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months before the start of study treatment;

Sponsors & Collaborators

• Fudan University: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Albumin-Bound Paclitaxel; Doxorubicin; Cyclophosphamide; Epirubicin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Zhimin Shao, MD,PhD

  Breast cancer institute of Fudan University Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhimin Shao, MD, PhD

CONTACT

+86-021-64175590; zhimingshao@yahoo.com

Li Chen, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 4, 2024
• First Posted: May 8, 2024
• Study Start: May 6, 2024
• Primary Completion: November 6, 2025
• Study Completion (Estimated): November 6, 2030
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share