Study Stopped
Business Decision
A Study of SY-1365 in Adult Patients With Advanced Solid Tumors
A Phase 1 Study of SY-1365, a Selective CDK7 Inhibitor, in Adult Patients With Advanced Solid Tumors
1 other identifier
interventional
107
3 countries
20
Brief Summary
This study consists of two parts. Part 1 is a dose-escalation/safety evaluation to provisionally identify a dose and regimen of SY-1365 for further evaluation in Part 2. Following the identification of a recommended dose and regimen from Part 1, the study entered Part 2 to further evaluate safety and the antitumor activity of SY-1365 in patients with select solid tumors, and to confirm target engagement and downstream pathway impact in patients with any solid tumor histology.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2017
Typical duration for phase_1
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 19, 2017
CompletedFirst Posted
Study publicly available on registry
May 1, 2017
CompletedStudy Start
First participant enrolled
May 12, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 15, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
June 24, 2020
CompletedMarch 9, 2021
November 1, 2019
3 years
April 19, 2017
March 5, 2021
Conditions
Outcome Measures
Primary Outcomes (3)
(Part 1) First-cycle dose-limiting toxicities (DLTs)
Within 1 year
(Part 1) ECG QTc Interval
Within 1 year
(Part 1 and 2) Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Within 1 year
Secondary Outcomes (8)
Peak Plasma Concentration (Cmax) of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin (Part 2 only)
Within 1 year
Area under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-last) of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin (Part 2 only)
Within 1 year
Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-INF) of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin (Part 2 only)
Within 1 year
(Part 1 and 2) Terminal elimination half life (t1/2)
Within 1 year
(Part 1 and 2) Evaluate the PD effects of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin or fulvestrant (Part 2 only)
Within 1 year
- +3 more secondary outcomes
Study Arms (6)
Dose Escalation
EXPERIMENTALDose escalation phase to explore maximum tolerated dose across two dosing schedules. SY-1365 will be administered intravenously weekly and twice-weekly for 3 weeks of each 4-week cycle
Advanced Ovarian Cancer
EXPERIMENTALPatients with ovarian cancer previously treated with ≥ 3 prior lines of therapy (SY-1365 single agent)
Relapsed Ovarian Cancer
EXPERIMENTALPatients with ovarian cancer previously treated with ≥ 1 prior line of therapy including a platinum-based regimen (SY-1365 + carboplatin)
Clear Cell Ovarian Cancer
EXPERIMENTALPatients with clear cell ovarian cancer previously treated with ≥ 1 prior line of therapy (SY-1365 single agent)
Advanced Solid Tumors
EXPERIMENTALBiopsy cohort of approximately 20-30 patients with advanced solid tumors from whom pre- and post-treatment biopsies will be obtained (SY-1365 single agent)
HR+ breast cancer
EXPERIMENTALPatients 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 (SY-1365 + fulvestrant)
Interventions
Two dosing schedules will be evaluated in dose escalation and a dose(s)/schedule(s) will be determined for Part 2: * Twice weekly: SY-1365 will be administered by intravenous infusion over 1 or 2 hours twice a week for 3 weeks of each 4 week (28 day) cycle. * Weekly: SY-1365 will be administered by intravenous infusion over 1 or 2 hours once a week for 3 weeks of each 4 week (28 day) cycle.
Carboplatin will be administered on Day 1 of each 3 week (21-day) cycle (Part 2 only)
Fulvestrant will be administered as an intramuscular (IM) dose of 500 mg every 2 weeks for the first 3 doses on Day 1 and Day 15 of the first 28-day cycle (Cycle 1), and on Day 1 of the second 28 day cycle (Cycle 2), and monthly thereafter starting on Day 1 of Cycle 3 (Part 2 only)
In combination with carboplatin, SY-1365 will be administered by intravenous infusion over 1 or 2 hours for 2 weeks of each 3 week (21-day) cycle (Part 2 only)
In combination with fulvestrant, SY-1365 will be administered by intravenous infusion over 1 or 2 hours once a week for 3 weeks of each 4 week (28-day) cycle (Part 2 only)
SY-1365 will be administered by intravenous infusion over 1 or 2 hours twice a week for 3 weeks of each 4 week (28 day) cycle
Eligibility Criteria
You may qualify if:
- years of age or older
- Disease status
- Part 1: any histologically-confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
- Part 2, Cohorts 1 and 2, all patients must have a histologically-confirmed diagnosis of high grade serous ovarian cancer (including fallopian tube cancer and/or primary peritoneal cancer)
- Part 2, Cohort 1, patients must have received ≥ 3 prior treatment regimens for ovarian cancer including a platinum-based regimen. Patients whose ovarian cancer harbors a mutation in breast cancer gene (BRCA), either germline or somatic, must have been previously treated with a poly(ADP ribose) polymerase (PARP) inhibitor, or be considered unwilling or ineligible for treatment with a PARP inhibitor
- Part 2, Cohort 2, patients must have received ≥ 1 prior treatment regimen for ovarian cancer, at least 1 of which is a platinum-based regimen
- Part 2,Cohort 3, all patients must have a histologically-confirmed diagnosis of clear cell ovarian cancer and must have received ≥ 1 prior treatment regimen for clear cell ovarian cancer, at least 1 of which is a platinum-based regimen.
- Part 2, Cohort 4, any histologically-confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective. Must have accessible tumor tissue and be willing to undergo tumor tissue sampling (biopsies/aspirates) pre-, during, and post-treatment
- At least 1 measurable lesion by RECIST 1.1
- All toxicities (except alopecia) from prior cancer treatments must have resolved to ≤ Grade 1 or returned to baseline levels prior to enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Life expectancy \> 3 months
- Absolute neutrophil count: ≥ 1.5 x 10\^9/L
- Platelets: ≥ 100 x 10\^9/L
- Hemoglobin: ≥ 9 g/dL
- +4 more criteria
You may not qualify if:
- Chemotherapy or limited field radiotherapy within 2 weeks, wide field radiotherapy within 4 weeks, or nitrosoureas or mitomycin C within 6 weeks prior to entering the study
- Major surgery within 2 weeks of 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 prior to enrollment, or \< 5 half-lives since completion of previous investigational therapy, whichever is shorter
- Received previous non-cytotoxic, FDA-approved anticancer agent within previous 2 weeks, or \< 5 half-lives since completion of previous therapy, whichever is shorter
- Prior exposure to transcriptional kinase family CDK inhibitors, such as the CDK7 and CDK9 inhibitors alvocidib (Flavopiridol), dinaciclib, and seliciclib. Exception: previous exposure to cell cycle CDK inhibitors such as CDK4 and CDK6 (eg, palbociclib) is allowed
- Known brain metastases or carcinomatous meningitis. Exception: previously treated brain metastatic disease that remains stable on MRI ≥ 4 weeks prior to enrollment without steroids or anti-epileptic medications
- History of allergic reactions attributed to compounds of similar chemical composition to SY-1365
- Immunocompromised patients with increased risk of opportunistic infections, including known HIV-positive patients
- Patients with known active Hepatitis B or Hepatitis C infection
- Prior treatment (\< 2 weeks before start of SY-1365) with moderate or strong CYP3A4 inducers or strong CYP3A4 inhibitors
- Baseline QT interval corrected with Fridericia's method (QTcF) \> 480 ms. NOTE: criterion does not apply to patients with a right or left bundle branch block (QTc interval)
- Significant cardiac risk, including: History of clinically significant cardiac disease or clinically relevant uncontrolled cardiac risk factors
- Uncontrolled intercurrent illness
- Part 2 Only:
- Cohorts 1 and 2: Patients with low-grade ovarian cancer (eg, low grade serous, mucinous carcinoma) are not eligible
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (20)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Honor Health Research Institute
Scottsdale, Arizona, 85258, United States
Palo Alto Medical Foundation Group
San Francisco, California, 94118, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Columbia University Medical Center
New York, New York, 10032, United States
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104, United States
Willamette Valley Cancer Institute and Research Center
Eugene, Oregon, 97401, United States
Women and Infants Hospital of Rhode Island
Providence, Rhode Island, 02905, United States
Tennessee Oncology
Nashville, Tennessee, 37203, United States
Texas Oncology
Austin, Texas, 78705, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Texas Oncology
Fort Worth, Texas, 76104, United States
South Texas Accelerated Research Therapeutics
San Antonio, Texas, 78229, United States
Hamilton Health Sciences
Hamilton, Ontario, L8V 1C3, Canada
McGill University Health Center
Montreal, Quebec, H4A 3J1, Canada
Centre Léon Bérard
Lyon, 69373 Lyon Cedex, France
Institut de Cancérologie de l'Ouest
Saint-Herblain, 44805 Saint Herblain Cedex, France
Institut Gustave Roussy
Villejuif, 94805 Villejuif Cedex, France
Related Publications (1)
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.
PMID: 32385714DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Kate Madigan, MD
Syros Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 19, 2017
First Posted
May 1, 2017
Study Start
May 12, 2017
Primary Completion
May 15, 2020
Study Completion
June 24, 2020
Last Updated
March 9, 2021
Record last verified: 2019-11