Trial Title:
Efficacy and Safety Study of Disitamab Vedotin + RC148 vs. Albumin-Paclitaxone ± Toripalimab in HR-/HER2-low Breast Cancer
NCT ID:
NCT06642545
Condition:
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Disitamab vedotin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Disitamab Vedotin
Description:
Disitamab Vedotin 2.0mg/kg,intravenous infusion, every 2 weeks
Arm group label:
Disitamab Vedotin +RC148
Other name:
RC48
Intervention type:
Drug
Intervention name:
RC148
Description:
20mg/kg, intravenous infusion, once every 2 weeks
Arm group label:
Disitamab Vedotin +RC148
Intervention type:
Drug
Intervention name:
Albumin-bound Paclitaxone
Description:
125 mg/m2,intravenous infusion, D1-8, every 3 weeks
Arm group label:
Albumin-bound Paclitaxone OR Albumin-bound Paclitaxone +Toripalimab
Intervention type:
Drug
Intervention name:
Toripalimab
Description:
240mg,intravenous infusion, once every 3 weeks
Arm group label:
Albumin-bound Paclitaxone OR Albumin-bound Paclitaxone +Toripalimab
Other name:
JS001
Summary:
Evaluating the Efficacy of Disitamab Vedotin in Combination with RC148 Compared to
Albumin-bound Paclitaxone Monotherapy or in Combination with Toripalimab for Subjects
with HR-negative, HER2-low Expressing Unresectable Locally Advanced or Metastatic Breast
Cancer
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Voluntarily agree to participate in the study and sign the informed consent form
- Stage III unresectable locally advanced or Stage IV metastatic breast cancer.
- Subjects must be willing and able to provide a tumor tissue block and/or unstained
pathology slides, with priority given to the most recent metastatic lesions that
have not previously been subjected to radiotherapy. If this is not feasible or
available, then a tumor tissue block (or fresh tissue sections) obtained from
locally recurrent lesions should be provided. Freshly obtained tissue is preferred
over archived tissue. The provided tissue will be used for biomarker testing and
must be suitable for analysis of HER2 expression and PD-L1 expression
- Invasive breast tumor tissue has been confirmed as HER2 low expression by the
central laboratory
- Invasive tumor tissue is negative for hormone receptors (HR), defined as
immunohistochemistry (IHC) testing showing that the proportion of cells with
positive nuclear staining for both ER and PgR in invasive cancer is less than 1%.
For patients with weakly positive ER/PgR (1% to 10% of tumor cell nuclei positive),
those who are not suitable for endocrine therapy after thorough evaluation by the
investigator, and with approval from the sponsor after communication, may be
included in this study
- For HR-negative, HER2-low expressing unresectable locally advanced or metastatic
breast cancer: locally recurrent and unresectable or previously untreated metastatic
breast cancer; or those who have completed curative treatment (excluding
radiotherapy) (e.g., the date of surgery for the primary breast tumor or the last
date of adjuvant therapy administration, whichever is later), with an interval of ≥6
months from the first documented local or distant disease recurrence. For subjects
who received taxane drugs during the (neo)adjuvant therapy phase, there must be an
interval of ≥12 months from the last taxane administration
- ECOG performance status of 0 or 1
- According to the RECIST v1.1 criteria, there must be at least one measurable lesion
(for lesions that have previously been irradiated, if the lesion can be measured
according to the RECIST v1.1 criteria and there is evidence of significant
progression after radiotherapy, the lesion can be considered a target lesion)
- Expected survival of at least 12 weeks
- Hematologic and organ function criteria to be met within 7 days prior to the first
dose of study medication (with normal values based on the clinical trial center's
standards, and no blood transfusions, hematopoietic growth factors, albumin, or
blood products within 14 days prior to the test):
Hemoglobin ≥ 90 g/L Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L Platelet count ≥ 100 ×
10^9/L Total bilirubin ≤ 1.5 × upper limit of normal (ULN) or direct bilirubin ≤ ULN (for
subjects with total bilirubin > 1.5 × ULN). Total bilirubin ≤ 3 × ULN (for subjects with
Gilbert's disease) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤
2.5 × ULN or ≤ 5 × ULN (if liver metastases are present) International normalized ratio
(INR), prothrombin time (PT), and activated partial thromboplastin time (APTT) ≤ 1.5 ×
ULN Creatinine clearance (CrCl) calculated by the Cockcroft-Gault formula ≥ 40 mL/min, or
serum creatinine ≤ 1.5 × ULN Urine routine test shows urine protein < 2+; if urine
protein ≥ 2+, the 24-hour urine protein quantification result must be < 1 g.
- Female subjects of childbearing potential who meet the following conditions:
A serum pregnancy test (with a minimum sensitivity of 25 mIU/mL or equivalent units of
β-human chorionic gonadotropin [β-hCG]) must be negative within 7 days prior to the first
dose of study intervention. Subjects with a false-positive result that is confirmed not
to be pregnant are eligible to participate in the study.
Must agree to use contraception during the study and for at least 6 months after the last
dose of study medication. No breastfeeding or egg donation within 6 months.
If sexual activity could lead to pregnancy, they must use at least one acceptable form of
contraception from the time of informed consent until at least 6 months after the last
dose of study medication.
- Male subjects of childbearing potential who meet the following conditions:
Must agree to abstain from donating sperm from the start of the study until at least 6
months after the last dose of study medication.
If having sexual intercourse with a person of childbearing potential that could lead to
pregnancy, must consistently use at least one acceptable form of contraception throughout
the study and for at least 6 months after the last dose of study medication.
If having sexual intercourse with a pregnant or breastfeeding partner, must use condoms
from the time of informed consent until at least 6 months after the last dose of study
medication.
- Capable of understanding the trial requirements and willing and able to comply with
the trial and follow-up procedures.
Exclusion Criteria:
- Having previously received anti-HER2 treatment, including ADC (Antibody-Drug
Conjugates).
- Having previously received immunotherapy, including anti PD-(L)1 or anti PD-(L)2
drugs, or drugs that directly target another stimulatory or co-inhibitory T-cell
receptor (such as CD137, CTLA-4, OX-40) during the locally advanced or metastatic
stage (except if the last administration was ≥12 months prior to recurrence or
progression, using [neo]adjuvant anti PD-(L)1).
- Excluding subjects with brain metastases or leptomeningeal metastases. Subjects with
treated brain metastases (surgery and/or radiotherapy) are eligible for inclusion if
they meet the following criteria:
Subjects who have received treatment for brain metastases may be considered for
participation in this study if they have not experienced disease progression as
determined by imaging studies within 4 weeks prior to the first dose of study treatment.
They must have discontinued the use of corticosteroids or anticonvulsant therapy at least
14 days before the first dose of study
- Use of investigational drugs or undergoing major surgery within 4 weeks prior to the
first dose of study medication
- Received or plan to receive live vaccines or attenuated live vaccines within 4 weeks
prior to the first dose of study medication or during the study period
- History of allogeneic hematopoietic stem cell transplantation or organ
transplantation
- Uncontrolled or significant cardiovascular or cerebrovascular disease, including
(but not limited to):
Within 6 months prior to the first dose of study medication, any of the following
occurred: congestive heart failure (NYHA Class III or IV), myocardial infarction, or
cerebral infarction (except for lacunar infarction), pulmonary embolism, unstable angina,
or the presence of arrhythmias requiring treatment at screening; Primary cardiomyopathy
(such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right
ventricular cardiomyopathy, restrictive cardiomyopathy, unclassified cardiomyopathy); A
history of clinically significant QTc interval prolongation, second-degree type II
atrioventricular block or third-degree atrioventricular block, or QTc interval
(Fridericia's formula) > 470 msec (females) or > 450 msec (males); Atrial fibrillation
(EHRA classification ≥ class 2b); Uncontrolled hypertension, as judged by the
investigator to be unsuitable for participation in the study
- Presence of clinically uncontrollable third space fluid accumulation, such as large
amounts of pleural effusion, pericardial effusion, or ascites that are associated
with clinical symptoms or require symptomatic treatment.
- History of interstitial lung disease that requires treatment or current severe
pulmonary disease, including but not limited to active pulmonary tuberculosis,
interstitial lung disease, etc.
- A clear history of neurological or psychiatric disorders, either past or present,
including epilepsy or dementia, etc.
- Toxicities from previous anti-cancer treatments have not yet recovered to grade 0-1
of the National Cancer Institute Common Terminology Criteria for Adverse Events
version 5.0 (NCI CTCAE v5.0), except for alopecia, hyperpigmentation, or other
conditions that the investigator deems do not increase the risk to the subject from
treatment.
- Persistent grade ≥2 sensory or motor neuropathy.
- Active infections that require systemic treatment:
Active infections requiring systemic treatment within 7 days prior to the first dose,
routine antimicrobial prophylaxis is allowed; Positive HIV test results; Patients with
active hepatitis B or C (HBsAg positive with detectable HBV DNA levels above the upper
limit of normal; HCVAb positive with detectable HCV RNA levels above the upper limit of
normal).
- Having active autoimmune diseases within the past 2 years that require systemic
treatment (such as corticosteroids or immunosuppressive drugs), except for
replacement therapies (such as thyroid hormone, insulin, or physiologic
corticosteroid replacement for adrenal or pituitary insufficiency).
- Having other malignant tumors within 5 years prior to signing the informed consent
form (except for effectively treated non-melanoma skin cancer, cervical carcinoma in
situ, localized prostate cancer, stage I endometrial cancer, or other tumors that
are considered cured).
- Known hypersensitivity or delayed-type allergic reactions to certain components of
Disitamab Vedotin, Toripalimab, RC148, or albumin-bound paclitaxone, or similar
drugs.
- According to the investigator's judgment, there are serious concomitant diseases
that could endanger the subject's safety or affect the subject's ability to complete
the clinical study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Cance Hosoltal Chinese Academy of Medical Sciences
Address:
City:
Beijing
Country:
China
Contact:
Last name:
Xin Wang
Phone:
010-87787170
Email:
WXCAMS@126.com
Start date:
November 1, 2024
Completion date:
October 1, 2027
Lead sponsor:
Agency:
RemeGen Co., Ltd.
Agency class:
Industry
Source:
RemeGen Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06642545
