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

October 26, 2023 updated by: Syros Pharmaceuticals

A Phase 1 Study of SY 5609, an Oral, Selective CDK7 Inhibitor, in Adult Patients With Select 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) .

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
105

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Senior Clinical Trial Manager
  • Phone Number: 857-321-8698
  • Email: gcraig@syros.com

Study Contact Backup

  • Name: Vice President Clinical Operations

Study Locations

  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner MD Anderson Cancer Center
    • California
      • Los Angeles, California, United States, 90095
        • University of California Los Angeles
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
    • Florida
      • Orlando, Florida, United States, 32806
        • Orlando Health Cancer Institute
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • The University of Iowa
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins University
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
      • Grand Rapids, Michigan, United States, 49546
        • START Midwest, LLC
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Duke University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Stephenson Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Sidney Kimmel Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute - Tennessee Oncology
    • Texas
      • San Antonio, Texas, United States, 78229
        • South Texas Accelerated Research Theraputics (START), LLC

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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. 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).
  4. Participants with histologically or cytologically confirmed PDAC with measurable metastatic lesion(s) (Groups 3 and 4 only).
  5. Participants must have at least 1 measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
  6. All toxicities (except alopecia) from prior cancer treatments must have resolved to ≤ Grade 1 before enrollment.
  7. For women of childbearing potential (WCBP): negative serum β human chorionic gonadotropin pregnancy test within 1 week before the first dose of SY 5609
  8. Adequate organ and marrow function
  9. Participants must be willing and able to comply with all aspects of the protocol
  10. Participants must provide written informed consent before any study-specific screening procedures.
  11. Albumin ≥ 3.0 grams/deciliters (g/dL) (Groups 3 and 4 only).

Exclusion Criteria:

  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
  2. 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
  3. Received any other investigational agents within 4 weeks before enrollment, or < 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 2 weeks, or < 5 half-lives since completion of previous therapy, whichever is shorter
  5. Known brain metastases or carcinomatous meningitis
  6. Immunocompromised participants with increased risk of opportunistic infections
  7. 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.

  8. 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)

  9. Female participants who are pregnant or breastfeeding
  10. History of clinically significant cardiac disease or clinically relevant uncontrolled cardiac risk factors
  11. Uncontrolled intercurrent illness.
  12. Poorly controlled ascites requiring paracentesis within 1 month prior to entering the study. (Groups 3 and 4 only)

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 combination with hormonal therapy will receive SY-5609 in combination with fulvestrant.
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-5609 in combination with gemcitabine at the recommended combination dose.
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 clinical activity of SY-5609 in combination with gemcitabine plus nab-paclitaxel at the recommended combination dose.
Drug: SY-5609
An oral CDK7 Inhibitor
Drug: Gemcitabine
Nucleoside metabolic inhibitor
Drug: Nab-paclitaxel
Taxane-type chemotherapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Groups 1 and 2: Dose-Limiting Toxicity of SY-5609
Time Frame: Up to 28 days after first administration
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)
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
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)
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
Up to 1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
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)
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)
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)
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)
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)
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)
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)
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
Up to 1 year
Groups 3 and 4 (Safety Lead-ins): Objective Response Rate (ORR)
Time Frame: Up to 1 year
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
Time Frame: Up to 1 year
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
Time Frame: Up to 1 year
Up to 1 year
Groups 3 and 4 (Safety Lead-ins): Time to Response
Time Frame: Up to 1 year
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
Time Frame: Up to 1 year
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
Time Frame: Up to 1 year
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
Time Frame: Up to 1 year
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
Time Frame: Up to 1 year
Up to 1 year
Groups 3 and 4 (Expansions): Time to Response
Time Frame: Up to 1 year
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
Time Frame: Up to 1 year
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

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Syros Pharmaceuticals

Publications and helpful links

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

General Publications

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 Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 23, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 31, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 30, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 22, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 27, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 29, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 27, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 26, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SY-5609-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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