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Poster display session

232P - Early Results from the Phase I Study of SY-1365, a Potent and Selective CDK7 inhibitor, in Patients with Ovarian Cancer and Advanced Solid Tumors


23 Nov 2019


Poster display session


Tumour Site

Ovarian Cancer


Debra Richardson


D.L. Richardson1, G.I. Shapiro2, K.T. Do2, C.A. Leath, III3, J.C. Sachdev4, J. Melear5, E. Hamilton6, G. Fleming7, C. Mathews8, J. Hou9, C.K. Anderson10, K. Papadopoulos11, J. Chan12, D.S. Miller13, S.L. Richey14, S. Mathews15, D. Ngo15, G. Hodgson15, D. Roth15, D. Juric16

Author affiliations

  • 1 Medical Oncology, Stephenson Cancer Centre, 73104 - Oklahoma City/US
  • 2 Medical Oncology, Dana-Farber Cancer Institute, Boston/US
  • 3 Medical Oncology, University of Alabama, Tuscaloosa/US
  • 4 Breast And Gyn Cancers Early Phase Clinical Trials, Virginia G. Piper Cancer Center Clinical Trials, AZ 85258 - Scottsdale/US
  • 5 Medical Oncology, Texas Oncology, Austin/US
  • 6 Medical Oncology, Sarah Cannon Research Institute and Tennessee Oncology, Nashville/US
  • 7 Medical Oncology, University of Chicago Department of Medicine - Section of Hematology/Oncology, 60637-1470 - Chicago/US
  • 8 Medical Oncology, Women and Infants of Rhode Island, Providence/US
  • 9 Medical Oncology, Columbia University Medical Center, New York/US
  • 10 Medical Oncology, Willamette Valley Cancer Institute and Research Center, Eugene/US
  • 11 Medical Oncology, South Texas Accelerated Research Therapeutics (START), 78229 - San Antonio/US
  • 12 Medical Oncology, Sutter Health, Sacramento/US
  • 13 Medical Oncology, UT Southwestern Medical, Dallas/US
  • 14 Medical Oncology, Texas Oncology, Fort Worth/US
  • 15 Research And Development, Syros Pharmaceuticals, 02139 - Cambridge/US
  • 16 Medical Oncology, Massachusetts General Hospital, Boston/US


Abstract 232P


SY-1365 is a first-in-class, potent, selective covalent CDK7 inhibitor currently under phase I evaluation in expansion cohorts including ovarian cancer (OC) patients (pts) to assess safety, biologic and anti-tumor activity of SY-1365 alone and in combination with carboplatin (CP), and correlation of activity with RB pathway changes (RbC).


Expansion cohort pts received single agent (SA) SY-1365 BIW at doses ranging from 53-80 mg/m2 administered IV over 1 or 2 hrs for 3 of 4 wks/cycle. CP was given at AUC4 or 5 on day 1 of a 3 wk cycle with SY-1365 at 53 mg/m2 QW days 1 and 8. Clinical activity and safety were assessed by RECIST 1.1 and CTCAEv5, respectively. Apoptotic and cell proliferation markers were evaluated in tumor tissue from pts with paired biopsies. RbC in tumor and plasma samples were evaluated for correlation with SY-1365 activity.


As of 6/14/19, 80 total pts were enrolled, 33 in dose escalation, and 47 in expansion cohorts including 15 receiving SA and 3 receiving SY-1365+CP that were evaluated for response. Overall median duration (N=80) on SY-1365 treatment was 30.5 days (1-232). Adverse events (AEs) were generally low grade and reversible, occurring mostly on the day of dosing. Frequent (≥15%) AEs of any causality included headache, nausea, vomiting, fatigue, diarrhea, decreased appetite, abdominal pain, thrombocytopenia, anemia, infusion-related reaction, and dehydration. There were no treatment-related deaths. Of the expansion pts evaluated for response, 33% (5/15) receiving SA and 100% (3/3) receiving SY-1365+CP had SD as the best response, with the longest pt on SA for 114 days and on CP combination for 232 days. Available tumor biopsies demonstrate evidence of apoptosis in post-dose tumor tissue in 3 of 4 pts, with early evidence of RbC associated with SD in OC pts.


Emerging tolerability findings suggest predominantly low grade, reversible AEs, primarily on days of dosing. Early clinical activity demonstrates SD in both SA and CP combination cohorts with evidence supporting increased apoptosis in tumor tissue and associations of clinical activity with RbC. PK/PD guided dose optimization is in progress. Updated data will be presented.

Clinical trial identification

NCT03134638 - May 1, 2017

Editorial acknowledgement

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