A two-part phase I study with the antibody-drug conjugate SYD985 in combination with niraparib to evaluate safety, pharmacokinetics and efficacy in patients with HER2-expressing locally advanced or metastatic solid tumours.
- Conditions
- Solid tumours (Study Part 1: solid tumours of any originStudy Part 2: breast cancer, ovarian cancer or endometrial carcinoma/carcinosarcomacancersolid tumours10027656
- Registration Number
- NL-OMON52764
- Lead Sponsor
- Byondis BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
The study population will consist of patients with locally advanced or
metastatic solid tumours, complying with the following in- and exclusion
criteria: 1. Male or female, age >= 18 years at the time of
signing first informed consent; 2. Patient with a histologically-confirmed,
locally advanced or metastatic tumour who has progressed on standard therapy or
for whom no standard therapy exists, with the following restriction: Part 1:
solid tumours of any origin; Part 2: breast cancer, ovarian cancer or
endometrial carcinoma/carcinosarcoma; 3. HER2 tumour status at least 1+ as
assessed by immunohistochemistry (IHC) as determined by the local laboratory;
4. Presence of a tumour lesion accessible for biopsy and patient should be
willing to undergo a fresh biopsy for central HER2 testing and genetic testing,
unless adequate (biopsy) tumour material is available obtained < 6 months prior
to signing the main informed consent; 5. At least one measurable cancer lesion
as defined by the Response Evaluation Criteria for Solid Tumours (RECIST
version 1.1); 6. Eastern Cooperative Oncology Group (ECOG) performance status <=
1; 7. Adequate organ function, evidenced by the following laboratory results:
- Absolute neutrophil count >= 1.5 x 109/L; - Platelet count >= 100 x 109/L; -
Hemoglobin >= 10.0 g/dL or 6.2 mmol/L; - 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; 8. For women of childbearing
potential and male patients with a female partner of childbearing potential,
highly effective contraception must be used during the study and up to 6 months
after last IMP 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. DUBA-containing ADCs at
any time; b. Anthracycline treatment within 8 weeks prior to start of study
treatment; c. Other anticancer therapy including chemotherapy, immunotherapy,
or investigational agents within 4 weeks prior to start of study treatment or 5
times the half-life of the therapy, whichever is shorter; d. Radiotherapy
within 4 weeks prior to start of study treatment or within 1 week for
palliative care (as long as the lungs were not exposed); e. Hormone therapy
within 1 week prior to start of study treatment. 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 containing treatment, niraparib or excipients
of study drugs (e.g. lactose or tartrazine in niraparib) which led to permanent
discontinuation of the treatment; 3. History or presence of keratitis; 4. 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 trastuzumab
containing treatment leading to permanent discontinuation of treatment; 5.
History (within 6 months prior to start of study treatment) or presence of
clinically significant cardiovascular disease such as unstable angina,
congestive heart failure, myocardial infarction, uncontrolled hypertension, or
cardiac arrhythmia requiring medication; 6. History or presence 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; 7. Severe, uncontrolled systemic
disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic
disease) at screening; 8. Symptomatic brain metastases, brain metastasis
requiring steroids to manage symptoms or treatment for brain metastases within
8 weeks prior to start of study treatment; 9. Known active Hepatitis B, C or E
infection; 10. Major surgery within 4 weeks prior to start of study treatment;
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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoints:<br /><br><br /><br>The primary endpoint for Part 1 of the study is: • Incidence of Dose Limiting<br /><br>Toxicity (DLT).<br /><br><br /><br>The primary endpoint for Part 2 of the study is: • Objective Response Rate<br /><br>(ORR).<br /><br><br /><br>ORR is defined as the percentage of patients with a best overall tumour<br /><br>response of complete response (CR) or partial response (PR) according to RECIST<br /><br>1.1. </p><br>
- Secondary Outcome Measures
Name Time Method