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Advanced Solid TumorPhase 1NCT04247126

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

A Phase 1 study testing SY-5609, Fulvestrant and Gemcitabine in people with Advanced Solid Tumor and Breast Cancer, run by Syros Pharmaceuticals at 16 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
SY-5609, Fulvestrant and Gemcitabine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
105 participants
Where
16 sitesUnited States
Study dates
23 Jan 2020to 30 Mar 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 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.
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  • For women of childbearing potential (WCBP): negative serum β 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 ≥ 3.0 grams/deciliters (g/dL) (Groups 3 and 4 only).

Who cannot join

  • 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 < 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
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  • 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 participants 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)

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

United States16 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University

    Atlanta, Georgia, 30322

  • Johns Hopkins University

    Baltimore, Maryland, 21205

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Duke University

    Durham, North Carolina, 27705

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • START Midwest, LLC

    Grand Rapids, Michigan, 49546

  • The University of Iowa

    Iowa City, Iowa, 52242

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • University of California Los Angeles

    Los Angeles, California, 90095

  • Sarah Cannon Research Institute - Tennessee Oncology

    Nashville, Tennessee, 37203

  • Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • Orlando Health Cancer Institute

    Orlando, Florida, 32806

  • Sidney Kimmel Cancer Center

    Philadelphia, Pennsylvania, 19107

  • South Texas Accelerated Research Theraputics (START), LLC

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: 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) .

Being tested
SY-5609, Fulvestrant, Gemcitabine, Nab-paclitaxel
Medical subject headings
Breast Neoplasms, Small Cell Lung Carcinoma, Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04247126
Study groupRoleWhat they receive
Group 1: Single Agent Dose EscalationExperimentalDose escalation phase to explore maximum tolerated dose of SY-5609 given as a single agent.
Receives: Drug: SY-5609
Group 2: SY-5609 + FulvestrantExperimentalParticipants 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.
Receives: Drug: SY-5609; Drug: Fulvestrant
Group 3: SY-5609 + GemcitabineExperimentalParticipants 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.
Receives: Drug: SY-5609; Drug: Gemcitabine
Group 4: SY-5609 + Gemcitabine + Nab-paclitaxelExperimentalParticipants 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.
Receives: Drug: SY-5609; Drug: Gemcitabine; Drug: Nab-paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Groups 1 and 2: Dose-Limiting Toxicity of SY-5609

    Measured: Up to 28 days after first administration

  2. Groups 1 and 2: Number of Participants With Treatment Emergent Adverse Events

    Measured: From Baseline up to 30 days after last dose of study drug (up to 1 year)

  3. Groups 3 and 4 (Safety Lead-ins): Number of Participants With Dose-Limiting Toxicity

    Measured: Up to 28 days after first administration

  4. Groups 3 and 4 (Safety Lead-ins): Number of Participants With TEAEs

    Measured: From Baseline up to 30 days after last dose of study drug (up to 1 year)

  5. Groups 3 and 4 (Expansions): Progression Free Survival

    Measured: Up to 1 year

Secondary outcomes (19)

  1. Groups 1 and 2: Area Under The Concentration Versus Time Curve of SY-6509

    Measured: 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)

  2. Groups 1 and 2: Apparent Clearance of SY-5609

    Measured: 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)

  3. Groups 1 and 2: Apparent Volume of Distribution of SY-5609

    Measured: 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)

  4. Groups 1 and 2: Elimination Half-Life of SY-5609

    Measured: 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)

  5. Groups 1 and 2: Maximum Plasma Concentration (Cmax) of SY-5609

    Measured: 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)

  6. Groups 1 and 2: Time of Maximum Plasma Concentration (Tmax) of SY-5609

    Measured: 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)

  7. Groups 1 and 2: Minimum or Trough Plasma Concentration (Cmin) of SY-5609

    Measured: 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)

  8. Groups 1 and 2: Time of Minimum or Trough Plasma Concentration (Tmin) of SY-5609

    Measured: 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)

  9. Groups 3 and 4 (Safety Lead-ins): Progression Free Survival

    Measured: Up to 1 year

  10. 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).

    Measured: Up to 1 year

  11. 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).

    Measured: Up to 1 year

  12. Groups 3 and 4 (Safety Lead-ins): Disease Control Rate

    Measured: Up to 1 year

  13. 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.

    Measured: Up to 1 year

  14. 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.

    Measured: Up to 1 year

  15. 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).

    Measured: Up to 1 year

  16. Groups 3 and 4 (Expansions): Complete Response Rate

    CR rate is defined as proportion of participants who achieve CR (as determined by the investigator).

    Measured: Up to 1 year

  17. Groups 3 and 4 (Expansions): Disease Control Rate

    Measured: Up to 1 year

  18. 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.

    Measured: Up to 1 year

  19. 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.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jan 2020
  2. Study start23 Jan 2020
  3. Primary completion31 Jan 2023
  4. Study completion30 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
105 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04247126
Sponsor's protocol ID
SY-5609-101
Status last verified
Oct 2023
First submitted
22 Jan 2020
Last updated
27 Oct 2023
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 34726887

  • 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.

    PubMed 32385714

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SY-5609, Fulvestrant and Gemcitabine in people with Advanced Solid Tumor and Breast Cancer, run by Syros Pharmaceuticals at 16 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Groups 1 and 2: Dose-Limiting Toxicity of SY-5609 (time frame: Up to 28 days after first administration). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04247126, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2023.

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