Abstract 232P
Background
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).
Methods
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.
Results
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.
Conclusions
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
Resources from the same session
205P - Treatment pattern and outcomes of radium-223 (Ra223) in metastatic castration resistant prostate cancer (mCRPC): Retrospective cohort analysis from Hong Kong
Presenter: Darren Poon
Session: Poster display session
Resources:
Abstract
206P - Population-based validation of the risk stratification among prostate cancer patients
Presenter: Mu Xie
Session: Poster display session
Resources:
Abstract
211P - Adjuvant axitinib in Asian vs non-Asian patients with metastatic renal cell carcinoma (mRCC): ATLAS trial subgroup analysis
Presenter: Chi Fai Ng
Session: Poster display session
Resources:
Abstract
212P - Immunotherapy with nivolumab in metastatic renal cell carcinoma patients in India: Bringing a change in clinical practice
Presenter: Amit Rauthan
Session: Poster display session
Resources:
Abstract
213P - An observational retrospective real-world study of sarcomatoid renal cell carcinoma (sRCC) patients in an Asian cancer centre
Presenter: Ravindran Kanesvaran
Session: Poster display session
Resources:
Abstract
214P - Targeting epithelial-mesenchymal transition (EMT), novel strategy to delay resistance or re-sensitize renal cancer to Sunitinib
Presenter: Revati Sharma
Session: Poster display session
Resources:
Abstract
215P - Radiologic and pathologic tumour size variation in localized renal cell carcinoma and its implications
Presenter: Shanky Singh
Session: Poster display session
Resources:
Abstract
216P - Partial versus radical nephrectomy: 10- year long-term survival among patients with Wilms tumour
Presenter: Mira Mostafa
Session: Poster display session
Resources:
Abstract
217P - Neutrophil-to-lymphocyte ratio is a useful biomarker for predicting worse clinical outcome in chemo-resistant urothelial carcinoma patients treated with pembrolizumab
Presenter: Koichiro Ogihara
Session: Poster display session
Resources:
Abstract
219P - Long-term outcomes of bladder preservation in muscle-invasive bladder cancer patients
Presenter: Amanda Dania Satiti
Session: Poster display session
Resources:
Abstract