A Study Of SY 5609, A Selective CDK7 Inhibitor, In Advanced Solid Tumors

Study Overview

A Study of SY 5609, a Selective CDK7 Inhibitor, in Advanced Solid Tumors

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) .

N/A

Advanced Solid Tumor
Breast Cancer
Small-cell Lung Cancer
Pancreatic Cancer

DRUG: SY-5609
DRUG: Fulvestrant
DRUG: Gemcitabine
DRUG: Nab-paclitaxel

SY-5609-101

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2020-01-22	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2023-10-26
First Submitted that Met QC Criteria 2020-01-27	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2023-10-27
First Posted (ACTUAL) 2020-01-29	Results First Posted N/A	Last Verified 2023-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Group 1: Single Agent Dose Escalation Dose escalation phase to explore maximum tolerated dose of SY-5609 given as a single agent.	DRUG: SY-5609 An oral CDK7 Inhibitor
EXPERIMENTAL: Group 2: SY-5609 + Fulvestrant Participants with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) negative advanced or metastatic breast cancer (BC) that has progressed following prior treatment with a cyclin-dependent kinase (CDK)4/6 inhibitor in combina	DRUG: SY-5609 An oral CDK7 Inhibitor DRUG: Fulvestrant Estrogen receptor antagonist
EXPERIMENTAL: Group 3: SY-5609 + Gemcitabine Participants with PDAC will receive SY-5609 in combination with gemcitabine in Safety Lead-in to identify a recommended combination dose for the expansion. The expansion part will assess the safety, tolerability, and preliminary clinical activity of SY-56	DRUG: SY-5609 An oral CDK7 Inhibitor DRUG: Gemcitabine Nucleoside metabolic inhibitor
EXPERIMENTAL: Group 4: SY-5609 + Gemcitabine + Nab-paclitaxel Participants with PDAC will receive SY-5609 in combination with gemcitabine plus nab-paclitaxel in Safety Lead-in to identify a recommended combination dose for the expansion. The expansion part will assess the safety, tolerability, and preliminary clinic	DRUG: SY-5609 An oral CDK7 Inhibitor DRUG: Gemcitabine Nucleoside metabolic inhibitor DRUG: Nab-paclitaxel Taxane-type chemotherapy

Primary Outcome Measures	Measure Description	Time Frame
Groups 1 and 2: Dose-Limiting Toxicity of SY-5609		Up to 28 days after first administration
Groups 1 and 2: Number of Participants With Treatment Emergent Adverse Events		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		Up to 28 days after first administration
Groups 3 and 4 (Safety Lead-ins): Number of Participants With TEAEs		From Baseline up to 30 days after last dose of study drug (up to 1 year)
Groups 3 and 4 (Expansions): Progression Free Survival		Up to 1 year

Secondary Outcome Measures	Measure Description	Time Frame
Groups 1 and 2: Area Under The Concentration Versus Time Curve of SY-6509		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		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		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		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		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		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		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		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		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).	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).	Up to 1 year
Groups 3 and 4 (Safety Lead-ins): Disease Control Rate		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.	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.	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).	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).	Up to 1 year
Groups 3 and 4 (Expansions): Disease Control Rate		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.	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.	Up to 1 year

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Marineau JJ, Hamman KB, Hu S, Alnemy S, Mihalich J, Kabro A, Whitmore KM, Winter DK, Roy S, Ciblat S, Ke N, Savinainen A, Wilsily A, Malojcic G, Zahler R, Schmidt D, Bradley MJ, Waters NJ, Chuaqui C. Discovery of SY-5609: A Selective, Noncovalent Inhibitor of CDK7. J Med Chem. 2022 Jan 27;65(2):1458-1480. doi: 10.1021/acs.jmedchem.1c01171. Epub 2021 Nov 2.
Sava GP, Fan H, Coombes RC, Buluwela L, Ali S. CDK7 inhibitors as anticancer drugs. Cancer Metastasis Rev. 2020 Sep;39(3):805-823. doi: 10.1007/s10555-020-09885-8.

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