A multi-centre, open-label, randomized clinical trial comparing the efficacy and safety of the antibody-drug conjugate SYD985 to physician's choice in patients with HER2-positive unresectable locally advanced or metastatic breast cancer
- Conditions
- breast cancerHER-2 positive locally advanced or metastatic breast tumor10006291
- Registration Number
- NL-OMON55876
- Lead Sponsor
- Byondis BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 25
1. Female patients, age = 18 years old at the time of signing informed consent;
2. Patients with histologically-confirmed, unresectable locally advanced or
metastatic breast cancer;
3. Patients should have had either progression during or after at least two
HER2-targeting treatment regimens for locally advanced or metastatic disease or
progression during or after (ado-)trastuzumab emtansine treatment for locally
advanced or metastatic disease;
4. HER2-positive tumour status according to the ASCO-CAP guidelines (defined as
a 3+ score on immunohistochemistry (IHC) and/or positive by in situ
hybridization (ISH)) confirmed by the central laboratory;
5. Patients must have measurable or non-measurable disease that is evaluable
per Response Evaluation Criteria for Solid Tumours (RECIST version 1.1).
Patients with bone-only sclerotic disease without a lytic component are not
eligible;
6. Eastern Cooperative Oncology Group (ECOG) performance status = 2;
7. Estimated life expectancy > 12 weeks at randomization;
8. Adequate organ function, evidenced by the following (local) laboratory
results:
- Absolute neutrophil count = 1.5 x 109 /L;
- Platelet count = 100 x 109 /L;
- Hemoglobin = 9.0 g/dL;
- Total bilirubin = 1.5 x the upper limit of normal (ULN);
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3.0x
ULN (or = 5.0x ULN in the presence of liver metastases);
- Serum creatinine = 1.5 x ULN;
9. For women of childbearing potential, two methods of effective contraception
must be used during the study and up to 6 months after last study treatment.
This is not required in case the patient or sole partner is surgically
sterilized or in case the patient truly abstains from sexual activity.
1. Having been treated with:
a. SYD985 at any time;
b. Anthracycline treatment within 12 weeks prior to randomization;
c. Other anticancer therapy including chemotherapy, immunotherapy, or
investigational agents within 4 weeks prior to randomization;
d. Radiotherapy within 2 weeks prior to randomization;
e. Hormone therapy within 1 week prior to randomization; The patient must have
sufficiently recovered from any treatment-related toxicities to NCI CTCAE Grade
=1 (except for toxicities not considered a safety risk for the patient at the
investigator*s discretion);
2. History of infusion-related reactions and/or hypersensitivity to
trastuzumab, (ado-)trastuzumab emtansine or excipients of the study drug which
led to permanent discontinuation of the treatment;
3. History of keratitis;
4. Severe, uncontrolled systemic disease (e.g. clinically significant
cardiovascular, pulmonary, or metabolic disease) at screening;
5. Left ventricular ejection fraction (LVEF) < 50% as assessed by either
echocardiography or multigated acquisition (MUGA) scan at screening, or a
history of clinically significant decrease in LVEF during previous treatment
with trastuzumab or (ado-)trastuzumab emtansine leading to permanent
discontinuation of treatment;
6. Cardiac troponin value above the ULN (local laboratory) at screening;
7. History (within 6 months prior to randomization) of clinically significant
cardiovascular disease such as unstable angina, congestive heart failure (CHF),
myocardial infarction, uncontrolled hypertension, or cardiac arrhythmia
requiring medication;
8. Untreated brain metastases, symptomatic brain metastases, brain metastases
requiring steroids to manage symptoms, or treatment for brain metastases within
8 weeks prior to randomization. Patients with prior treatment of brain
metastases must have evidence of disease stability on baseline brain imaging as
compared to historical brain imaging;
9. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g.
bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis,
or evidence of active pneumonitis on screening chest CT scan.
10. Known active Hepatitis B or C infection;
11. Major surgery within 4 weeks prior to randomization;
12. Pregnancy or lactation;
13. Other condition, which in the opinion of the investigator, would compromise
the safety of the patient or the patient's ability to complete the study
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoint is PFS based on blinded independent central<br /><br>review (ICR) of tumour assessment according to RECIST 1.1. PFS is defined as<br /><br>the time from the date of randomization to the date of first documented<br /><br>ICR-assessed disease progression according to RECIST 1.1 or death due to any<br /><br>cause (whichever occurs earlier).</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Overall Survival;<br /><br>- Objective Response Rate on the basis of the blinded independent central<br /><br>review;<br /><br>- Investigator assessed PFS;<br /><br>- Patient reported outcomes for health related quality of life;</p><br>