Phase I Study of SYD985 With Niraparib in Patients With Solid Tumors

• Male or female, age ≥ 18 years at the time of signing first informed consent;

• 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;
• HER2 tumor status at least 1+ as assessed by immunohistochemistry (IHC) as determined by the local laboratory;
• Presence of a tumor 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;
• At least one measurable cancer lesion as defined by the Response Evaluation Criteria for Solid Tumours (RECIST version 1.1);
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
• Adequate organ function.

Exclusion Criteria:

• Having been treated with:

  1. DUBA-containing ADCs at any time;
  2. Anthracycline treatment within 8 weeks prior to start of study treatment;
  3. 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;
  4. 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);
  5. 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);
• History or presence of keratitis;
• 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;
• 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;
• 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;
• Severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) at screening;
• Symptomatic brain metastases, brain metastasis requiring steroids to manage symptoms or treatment for brain metastases within 8 weeks prior to start of study treatment.