A Study of SY 5609, a Selective CDK7 Inhibitor, in Advanced Solid Tumors
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04247126 |
Recruitment Status :
Recruiting
First Posted : January 29, 2020
Last Update Posted : March 18, 2022
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Condition or disease | Intervention/treatment | Phase |
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Advanced Solid Tumor Breast Cancer Small-cell Lung Cancer Pancreatic Cancer | Drug: SY-5609 Drug: Fulvestrant Drug: Gemcitabine Drug: Nab-paclitaxel | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 160 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1 Study of SY 5609, an Oral, Selective CDK7 Inhibitor, in Adult Patients With Select Advanced Solid Tumors |
Actual Study Start Date : | January 23, 2020 |
Estimated Primary Completion Date : | July 2023 |
Estimated Study Completion Date : | July 2024 |

Arm | Intervention/treatment |
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Experimental: Group 1: Single Agent Dose Escalation
Dose escalation phase to explore maximum tolerated dose of SY-5609 given as a single agent.
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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.
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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.
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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.
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Drug: SY-5609
An oral CDK7 Inhibitor Drug: Gemcitabine Nucleoside metabolic inhibitor Drug: Nab-paclitaxel Taxane-type chemotherapy |
- 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) [ 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).
- 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).
- 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 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.
- 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.
- 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).
- 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).
- Groups 3 and 4 (Expansions): Disease Control Rate [ Time Frame: 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.
- 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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
- 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).
Exclusion Criteria:
- 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
- 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.
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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)

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04247126
Contact: Senior Clinical Trial Manager | 857-321-8698 | gcraig@syros.com | |
Contact: Vice President Clinical Operations |
United States, California | |
Cedars-Sinai Medical Center | Recruiting |
Los Angeles, California, United States, 90048 | |
Contact: Anna Rosen anna.rosen@cshs.org | |
Principal Investigator: Monica Mita, MD | |
United States, Florida | |
Orlando Health Cancer Institute | Recruiting |
Orlando, Florida, United States, 32806 | |
Contact: Kiera Grofsik kiera.grofsik@orlandohealth.com | |
Principal Investigator: Sajeve Thomas, MD | |
United States, Georgia | |
Emory University | Recruiting |
Atlanta, Georgia, United States, 30322 | |
Contact: Emma Judson ejudson@emory.edu | |
Principal Investigator: Mehmet Akce, MD | |
United States, Maryland | |
Johns Hopkins University | Recruiting |
Baltimore, Maryland, United States, 21205 | |
Contact: Clarissa Frimpong cfrimpo2@jhmi.edu | |
Principal Investigator: Jessica Tao, MD | |
United States, Massachusetts | |
Massachusetts General Hospital | Recruiting |
Boston, Massachusetts, United States, 02114 | |
Contact: Brittney Peterkin BPETERKIN@mgh.harvard.edu | |
Principal Investigator: Dejan Juric, MD | |
Dana Farber Cancer Institute | Recruiting |
Boston, Massachusetts, United States, 02215 | |
Contact: Illya Dixon Illya_Dixon@dfci.harvard.edu | |
Principal Investigator: Geoffrey Shapiro, MD | |
United States, Michigan | |
University of Michigan | Recruiting |
Ann Arbor, Michigan, United States, 48109 | |
Contact: Cliff Abat abatcn@med.umich.edu | |
Principal Investigator: Vaibhav Sahai, MD | |
START Midwest, LLC | Recruiting |
Grand Rapids, Michigan, United States, 49546 | |
Contact: Shannon Skibinski-Preston 616-954-5552 shannon.skibinski@startmidwest.com | |
Principal Investigator: Manish Sharma, MD | |
United States, North Carolina | |
Duke University | Recruiting |
Durham, North Carolina, United States, 27705 | |
Contact: Jeremy Jenkins jeremy.jenkins@duke.edu | |
Principal Investigator: Niharika Mettu, MD | |
United States, Oklahoma | |
Stephenson Cancer Center | Recruiting |
Oklahoma City, Oklahoma, United States, 73104 | |
Contact: Dana Low Dana-Low@ouhsc.edu | |
Principal Investigator: Debra Richardson, MD | |
United States, Pennsylvania | |
Sidney Kimmel Cancer Center | Recruiting |
Philadelphia, Pennsylvania, United States, 19107 | |
Contact: Allison Scott Allison.Scott@jefferson.edu | |
Principal Investigator: Babar Bashir, MD | |
United States, Tennessee | |
Sarah Cannon Research Institute - Tennessee Oncology | Recruiting |
Nashville, Tennessee, United States, 37203 | |
Contact: Jacquelyn Spence 615-340-2830 jacquelyn.spence@sarahcannon.com | |
Principal Investigator: Erika Hamilton, MD | |
United States, Texas | |
Mary Crowley Cancer Research | Recruiting |
Dallas, Texas, United States, 75230 | |
Principal Investigator: Douglas Orr, MD | |
South Texas Accelerated Research Theraputics (START), LLC | Recruiting |
San Antonio, Texas, United States, 78229 | |
Contact: Isabel Jimenez, RN, MSN 210-593-5265 isabel.jimenez@startsa.com | |
Principal Investigator: Kyriakos Papadopoulos, MD |
Responsible Party: | Syros Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT04247126 |
Other Study ID Numbers: |
SY-5609-101 |
First Posted: | January 29, 2020 Key Record Dates |
Last Update Posted: | March 18, 2022 |
Last Verified: | February 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Small Cell Lung Carcinoma Neoplasms Neoplasms by Site Carcinoma, Bronchogenic Bronchial Neoplasms Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Lung Diseases Respiratory Tract Diseases Gemcitabine Paclitaxel Fulvestrant Antineoplastic Agents, Phytogenic Antineoplastic Agents |
Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Hormonal Estrogen Receptor Antagonists Estrogen Antagonists |