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

NCT ID: NCT04247126

Last Updated: 2023-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

105 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-23

Study Completion Date

2023-03-30

Brief Summary

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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) .

Detailed Description

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Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group 1: Single Agent Dose Escalation

Dose escalation phase to explore maximum tolerated dose of SY-5609 given as a single agent.

Group Type EXPERIMENTAL

SY-5609

Intervention Type DRUG

An oral CDK7 Inhibitor

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.

Group Type EXPERIMENTAL

SY-5609

Intervention Type DRUG

An oral CDK7 Inhibitor

Fulvestrant

Intervention Type DRUG

Estrogen receptor antagonist

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.

Group Type EXPERIMENTAL

SY-5609

Intervention Type DRUG

An oral CDK7 Inhibitor

Gemcitabine

Intervention Type DRUG

Nucleoside metabolic inhibitor

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.

Group Type EXPERIMENTAL

SY-5609

Intervention Type DRUG

An oral CDK7 Inhibitor

Gemcitabine

Intervention Type DRUG

Nucleoside metabolic inhibitor

Nab-paclitaxel

Intervention Type DRUG

Taxane-type chemotherapy

Interventions

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SY-5609

An oral CDK7 Inhibitor

Intervention Type DRUG

Fulvestrant

Estrogen receptor antagonist

Intervention Type DRUG

Gemcitabine

Nucleoside metabolic inhibitor

Intervention Type DRUG

Nab-paclitaxel

Taxane-type chemotherapy

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Syros Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

University of California Los Angeles

Los Angeles, California, United States

Site Status

Orlando Health Cancer Institute

Orlando, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

The University of Iowa

Iowa City, Iowa, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

START Midwest, LLC

Grand Rapids, Michigan, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute - Tennessee Oncology

Nashville, Tennessee, United States

Site Status

South Texas Accelerated Research Theraputics (START), LLC

San Antonio, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 34726887 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32385714 (View on PubMed)

Other Identifiers

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SY-5609-101

Identifier Type: -

Identifier Source: org_study_id

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