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
370P - Tumour mutation burden analysis in a 5660-cancer-patient cohort reveals cancer type-specific mechanisms for high mutation burden
Presenter: Yuan-Sheng Zang
Session: Poster display session
Resources:
Abstract
371P - Clinical utility of Encyclopedic tumour analysis to treat patients advanced refractory head and neck cancers
Presenter: Rajnish Nagarkar
Session: Poster display session
Resources:
Abstract
372P - Real-world fusion landscape in advanced Chinese pancreatic cancer using next generation sequecing: A multicenter study
Presenter: Yiyu Shen
Session: Poster display session
Resources:
Abstract
373P - Molecular profiling of non-small cell lung cancer (NSCLC) in Asia with targeted next-generation sequencing (NGS): Interim analysis of a co-operative group study (ATORG-001)
Presenter: Aaron Tan
Session: Poster display session
Resources:
Abstract
374P - Circulating tumour DNA (ctDNA) identifies actionable genetic alterations in Middle Eastern and Asian (MEA) patients diagnosed with carcinoma of unknown primary (CUP)
Presenter: Nir Peled
Session: Poster display session
Resources:
Abstract
375P - Whole-exome sequencing of tumour-only samples reveals the association between somatic alterations and clinical features in pancreatic cancer
Presenter: Huixin Lin
Session: Poster display session
Resources:
Abstract
376P - Adoption of molecular testing in breast cancer in a tertiary care center in a developing country
Presenter: Prasanta Dash
Session: Poster display session
Resources:
Abstract
377P - NGS in advanced NSCLC in a developing country: Ready for prime time?
Presenter: Amrith B P
Session: Poster display session
Resources:
Abstract
378P - Germline BRCA1/2 testing: Trend in Tan Tock Seng Hospital Singapore
Presenter: Chia Wei Lim
Session: Poster display session
Resources:
Abstract
379P - Study of germline mutations in high risk cancer patients from a tertiary care center in India
Presenter: Padmaj Kulkarni
Session: Poster display session
Resources:
Abstract