The study consists of 2 parts. Part 1 is dose escalation and will first administer SY-5609 alone to participants with select advanced solid tumors and then in combination with fulvestrant to participants with HR positive, HER2-negative breast cancer. Part 2 is a dose expansion and will first administer SY-5609 in combination with gemcitabine and then SY-5609 in combination with gemcitabine and nab-paclitaxel in participants with pancreatic ductal adenocarcinoma (PDAC) .
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
105
An oral CDK7 Inhibitor
Estrogen receptor antagonist
Nucleoside metabolic inhibitor
Taxane-type chemotherapy
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
University of California Los Angeles
Los Angeles, California, United States
Orlando Health Cancer Institute
Orlando, Florida, United States
Emory University
Atlanta, Georgia, United States
The University of Iowa
Iowa City, Iowa, United States
Johns Hopkins University
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
...and 6 more locations
Groups 1 and 2: Dose-Limiting Toxicity of SY-5609
Time frame: Up to 28 days after first administration
Groups 1 and 2: Number of Participants With Treatment Emergent Adverse Events
Time frame: From Baseline up to 30 days after last dose of study drug (up to 1 year)
Groups 3 and 4 (Safety Lead-ins): Number of Participants With Dose-Limiting Toxicity
Time frame: Up to 28 days after first administration
Groups 3 and 4 (Safety Lead-ins): Number of Participants With TEAEs
Time frame: From Baseline up to 30 days after last dose of study drug (up to 1 year)
Groups 3 and 4 (Expansions): Progression Free Survival
Time frame: Up to 1 year
Groups 1 and 2: Area Under The Concentration Versus Time Curve of SY-6509
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Groups 1 and 2: Apparent Clearance of SY-5609
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Groups 1 and 2: Apparent Volume of Distribution of SY-5609
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Groups 1 and 2: Elimination Half-Life of SY-5609
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Groups 1 and 2: Maximum Plasma Concentration (Cmax) of SY-5609
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Groups 1 and 2: Time of Maximum Plasma Concentration (Tmax) of SY-5609
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Groups 1 and 2: Minimum or Trough Plasma Concentration (Cmin) of SY-5609
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Groups 1 and 2: Time of Minimum or Trough Plasma Concentration (Tmin) of SY-5609
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Groups 3 and 4 (Safety Lead-ins): Progression Free Survival
Time frame: Up to 1 year
Groups 3 and 4 (Safety Lead-ins): Objective Response Rate (ORR)
ORR is defined as the proportion of participants who achieve complete response (CR) and partial remission (PR) (as determined by the investigator).
Time frame: Up to 1 year
Groups 3 and 4 (Safety Lead-ins): Complete Response/Remission (CR) Rate
CR rate is defined as proportion of participants who achieve CR (as determined by the investigator).
Time frame: Up to 1 year
Groups 3 and 4 (Safety Lead-ins): Disease Control Rate
Time frame: Up to 1 year
Groups 3 and 4 (Safety Lead-ins): Time to Response
Time to response is defined as the duration from the date of randomization to the date of the first documented evidence of response as determined by the investigator.
Time frame: Up to 1 year
Groups 3 and 4 (Safety Lead-ins): Duration of Response
Duration of response is defined as duration from the date of first documented evidence of response to the date of relapse of disease (as determined by the investigator), or death due to any cause, whichever occurs first.
Time frame: Up to 1 year
Groups 3 and 4 (Expansions): Objective Response Rate
ORR is defined as the proportion of participants who achieve CR and partial remission (PR) (as determined by the investigator).
Time frame: Up to 1 year
Groups 3 and 4 (Expansions): Complete Response Rate
CR rate is defined as proportion of participants who achieve CR (as determined by the investigator).
Time frame: Up to 1 year
Groups 3 and 4 (Expansions): Disease Control Rate
Time frame: Up to 1 year
Groups 3 and 4 (Expansions): Time to Response
Time to response is defined as the duration from the date of randomization to the date of the first documented evidence of response as determined by the investigator.
Time frame: Up to 1 year
Groups 3 and 4 (Expansions): Duration of Response
Duration of response is defined as duration from the date of first documented evidence of response to the date of relapse of disease (as determined by the investigator), or death due to any cause, whichever occurs first.
Time frame: Up to 1 year
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