A Phase I Study of SY 5609, an Oral, Selective CDK7 Inhibitor, in Adult Patients With Select Advanced Solid Tumors
Considering participating in a START clinical trial?
Study Summary
To evaluate SY-5609 in patients with select solid tumors, including breast, lung and ovarian cancers and cancers of any histology defined by a specific molecular signature.
To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics, establish MTD of SY-5609 in patients with breast, colorectal, lung and ovarian cancers, as well as in patients with solid tumors of any histology harboring Rb pathway alterations.
To evaluate the activity of SY 5609 administration in humans with select advanced solid tumors.
To evaluate the safety, tolerability, and maximum tolerated dose (MTD) of SY-5609.
To characterize the pharmacokinetic (PK), pharmacodynamic (PD), and preliminary antitumor activity of SY-5609.
To explore candidate biomarkers predictive of response to SY-5609.
Part 1: To evaluate single agent SY-5609 in patients with select advanced solid tumors and in combination with fulvestrant in HR+ breast cancer.
Part 2: To evaluate the doublet regimen of SY-5609 and gemcitabine and the triplet regimen of SY-5609, gemcitabine and nab-paclitaxel in patients with PDAC in their second or third line of treatment.
To present data from the ongoing SA dose escalation and SY-5609 + gem +/- nab-paclitaxel (np) safety lead-ins (SLIs).
Evaluations included safety, clinical activity (RECIST v1.1), PK, and induction of peripheral blood PD marker POLR2A (Papadopoulos 2020).
- Age > or = 18 years
- Advanced Solid Tumors for which standard curative or palliative measures do not exist or are no longer effective. Group 1 only).
- Postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. Participants must have failed prior treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor in combination with hormonal therapy in a previous line of therapy (Group 2 only).
- Participants with histologically or cytologically confirmed PDAC with measurable metastatic lesion(s) (Groups 3 and 4 only).
- Participants must have at least 1 measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- All toxicities (except alopecia) from prior cancer treatments must have resolved to = Grade 1 before enrollment.
- For women of childbearing potential (WCBP): negative serum ß human chorionic gonadotropin pregnancy test within 1 week before the first dose of SY 5609
- Adequate organ and marrow function
- Participants must be willing and able to comply with all aspects of the protocol
- Participants must provide written informed consent before any study-specific screening procedures.
- Albumin > or = 3.0 grams/deciliters (g/dL) (Groups 3 and 4 only).
- SY-5609/Gem group: 2nd or 3rd line patients who have progressed following Folfirinox or modified Folfirinox
- SY-5609/Gem /Nab pac group: 2nd line patients who have progressed following Folfirinox or modified Folfirinox
- Atleast 1 measurable lesion bu Recist v1.1
- ECOG performance status 0/1
- Chemotherapy or limited field radiotherapy within 2 weeks, wide field radiotherapy within 4 weeks, or nitrosoureas or mitomycin C within 6 weeks before entering the study
- Major surgery within 2 weeks before starting the study treatment, or not recovered to baseline status from the effects of surgery received > 2 weeks prior
- Received any other investigational agents within 4 weeks before enrollment, or < five (5) half-lives since completion of previous investigational therapy, whichever is shorter
- Received previous noncytotoxic, US Food and Drug Administration-approved anticancer agent within previous 2 weeks, or < 5 half-lives since completion of previous therapy, whichever is shorter
- Known brain metastases or carcinomatous meningitis
- Immunocompromised participants with increased risk of opportunistic infections
- Participants with known active or chronic hepatitis B or active hepatitis C infection. Participants 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.
- Baseline QT interval corrected (QTc) with Fridericia's method > 480 milliseconds
- NOTE: criterion does not apply to participants with a right or left bundle branch block (QTc interval)
- Female patients who are pregnant or breastfeeding
- History of clinically significant cardiac disease or clinically relevant uncontrolled cardiac risk factors
- Uncontrolled intercurrent illness.
- Poorly controlled ascites requiring paracentesis within 1 month prior to entering the study. (Groups 3 and 4 only)
- Prior Transcriptional kinase family CDK inhibitors (CDK7, CDK9, and Pan CKD Inhibitors)
Clinical Study Information for Healthcare Providers
By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.