Trial Title:
QL1706 Plus Chemotherapy as Neoadjuvant Therapy in Early High-Risk ER+/HER2- Breast Cancer
NCT ID:
NCT06404463
Condition:
Early Breast Cancer
Neoadjuvant Therapy
HR+HER2- Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Paclitaxel
Cyclophosphamide
Doxorubicin
Epirubicin
Albumin-Bound Paclitaxel
Antibodies
Antibodies, Bispecific
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
QL1706 (bispecific antibody targeting PD-1 and CLTA-4)
Description:
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).
Arm group label:
QL1706
Intervention type:
Drug
Intervention name:
Albumin-bound paclitaxel
Description:
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.
Arm group label:
QL1706
Intervention type:
Drug
Intervention name:
Doxorubicin
Description:
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.
Arm group label:
QL1706
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
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.
Arm group label:
QL1706
Intervention type:
Drug
Intervention name:
Epirubicin
Description:
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.
Arm group label:
QL1706
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.
Detailed description:
This study is a single-arm, single-center, phase II clinical trial aimed at observing and
evaluating the effectiveness and safety of QL1706 combined with albumin-bound paclitaxel,
sequential AC (doxorubicin/cyclophosphamide) neoadjuvant therapy for early high-risk
ER+/HER2- breast cancer.
A total of 76 subjects are planned to be enrolled. After enrollment, subjects will
receive QL1706 combined with albumin-bound paclitaxel for 4 cycles followed by sequential
AC/EC treatment for 4 cycles. Each treatment cycle will span 3 weeks until the occurrence
of a specified treatment termination event, after which subjects will continue to undergo
postoperative efficacy and safety assessments.
Safety assessments will be conducted before each QL1706 treatment cycle. Imaging
evaluations will be performed every 2 cycles until completion of 8 cycles of treatment to
assess efficacy. Additional imaging assessments may be performed as clinically indicated
during the study. Tumor imaging assessments will continue until confirmed disease
progression according to RECIST v1.1 criteria, initiation of new anti-tumor therapy,
withdrawal of consent, or death, whichever occurs first.
Following treatment completion, a treatment completion visit will be conducted. Subjects
who discontinue treatment due to reasons other than RECIST v1.1-defined disease
progression will undergo regular tumor imaging assessment follow-ups to evaluate time to
disease progression. Subjects will also undergo survival follow-up visits every 6 months
(every 3 months in the first year and every 6 months thereafter) after treatment
completion to collect and record survival status and subsequent anti-tumor treatment
information.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Voluntarily join this study and sign the informed consent form;
2. 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;
3. According to RECIST 1.1, there is at least one measurable lesion;
4. ECOG score: 0~1;
5. Tumor tissue specimens that can be used for biomarker detection;
6. 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).
Exclusion Criteria:
1. 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);
2. 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;
3. Severe allergic reactions to other monoclonal antibodies;
4. Known history or evidence of interstitial lung disease or active non-infectious
pneumonia;
5. Those with known central nervous system metastasis;
6. 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);
7. 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;
8. 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);
9. Those who are receiving thrombolysis or anticoagulation therapy are allowed to use
low-dose aspirin and low-molecular-weight heparin prophylactically;
10. 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;
11. 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;
12. 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;
13. 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;
14. Known hereditary or acquired bleeding and thrombotic tendencies (such as hemophilia
patients, coagulation disorders, etc.);
15. Major vascular disease (for example, aortic aneurysm requiring surgical repair or
recent peripheral arterial thrombosis) within 6 months before the start of study
treatment;
16. Urine routine shows urine protein ≥ ++ and confirmed 24-hour urine protein amount
>1.0 g;
17. Suffering from active infection, unexplained fever ≥38.5℃ within 7 days before
taking the drug, or baseline white blood cell count >15×109/L;
18. Those with congenital or acquired immune deficiency (such as HIV infection); those
who are hepatitis B surface antigen (HBsAg) positive and hepatitis B virus
deoxyribonucleic acid (HBV DNA) ≥ 2000 IU/ml, or hepatitis C virus antibody
positive;
19. Have received live vaccines less than 4 weeks before study medication or may be
vaccinated during the study period;
20. In the judgment of the researcher, the patient has other factors that may affect the
study results or cause the study to be terminated midway, such as alcoholism, drug
abuse, other serious diseases (including mental illness) that require combined
treatment, and serious laboratory tests. Abnormalities, accompanied by family or
social factors, may affect the patient's safety.
Gender:
Female
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Start date:
May 6, 2024
Completion date:
November 6, 2030
Lead sponsor:
Agency:
Fudan University
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06404463
