Overview

This is a dose escalation study and will be the first to administer SY-5609 alone to humans with select advanced solid tumors and in combination with Fulvestrant to patients with HR positive, HER2-negative breast cancer.

Eligibility

Inclusion Criteria:

1. Age 18 years
2. Advanced Solid Tumors for which standard curative or palliative measures do not exist or are no longer effective (Group 1 only).
3. Postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. Patients must have failed prior treatment with a CDK 4/6 inhibitor in combination with hormonal therapy in a previous line of therapy (Group 2 only).
4. Patients must have at least one (1) measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
5. All toxicities (except alopecia) from prior cancer treatments must have resolved to Grade 1 before enrollment.
6. For women of childbearing potential (WCBP): negative serum human chorionic gonadotropin pregnancy test within 1 week before the first dose of SY 5609
7. Adequate organ and marrow function
8. Patients must be willing and able to comply with all aspects of the protocol
9. Patients must provide written informed consent before any study-specific screening procedures

Exclusion Criteria:

1. Chemotherapy or limited field radiotherapy within two (2) weeks, wide field radiotherapy within four (4) weeks, or nitrosoureas or mitomycin C within six (6) weeks before entering the study
2. Major surgery within two (2) weeks before starting the study treatment, or not recovered to baseline status from the effects of surgery received > two (2) weeks prior
3. Received any other investigational agents within 4 weeks before enrollment, or < five (5) half-lives since completion of previous investigational therapy, whichever is shorter
4. Received previous noncytotoxic, US Food and Drug Administration-approved anticancer agent within previous two (2) weeks, or < five (5) half-lives since completion of previous therapy, whichever is shorter
5. Known brain metastases or carcinomatous meningitis
6. Immunocompromised patients with increased risk of opportunistic infections
7. Patients with known active or chronic hepatitis B or active hepatitis C infection. Patients with a history of hepatitis C virus (HCV) infection who have completed curative therapy for HCV at least 12 weeks before Screening and have a documented undetectable viral load at Screening are eligible for enrollment.
8. Baseline QT interval corrected (QTc) with Fridericia's method > 480 ms
   • NOTE: criterion does not apply to patients with a right or left bundle branch block (QTc interval)
9. Female patients who are pregnant or breastfeeding
10. History of clinically significant cardiac disease or clinically relevant uncontrolled cardiac risk factors
11. Uncontrolled intercurrent illness