A study to compare the efficacy and safety of SYD985 to four standard available treatments in patients with HER2-positive unresectable locally advanced or metastatic breast cancer.

Phase 1

• Conditions: breast tumours; MedDRA version: 20.0Level: LLTClassification code 10006317Term: Breast tumour malignantSystem Organ Class: 100000020819; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-001994-18-ES
• Lead Sponsor: Synthon Biopharmaceuticals BV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-07-31
• Study Completion: 2022-06-30
• Last Update Posted: 16 October 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 437

Inclusion Criteria

Any patient must meet the following inclusion criteria:
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;
4. HER2-positive tumour status (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) <=3.0 x ULN (or <=5.0 x 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 258
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 87

Exclusion Criteria

Any patient who meets any of the exclusion criteria below must be excluded from participation in the study:
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 metastasis must have evidence of disease stability on baseline brain imaging as compared to historical brain imaging;
9. Known infection with HIV, or known active Hepatitis B or C infection;
10. Major surgery within 4 weeks prior to randomization;
11. Pregnancy or lactation;
12. 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 clinical trial of medicinal product
• Study Design: Not specified