Abstract 2921
Background
CXD101 is a histone–deacetylase inhibitor which reactivates the patient’s immune system by increasing tumour expression of MHC I & II, tumoural infiltration by CD8 lymphocytes and decreasing T Reg cells. CXD101 has been shown in a Phase I study conducted in the UK to have anti-tumour activity as monotherapy, and to be generally well tolerated.The anti-tumour efficacy of CXD101 has been investigated as monotherapy or in combination with the immune checkpoint inhibitors, anti-mouse PD-1 and anti-mouse CTLA4, respectively, in the syngeneic MSS Colon 26 model. The tumour Colon26 celles were implanted subcutaneously in immunocompetent BALB/c mice. The syngeneic tumour was seen to respond poorly to anti-PD1 and anti-CTLA4 immune therapeutics alone. As a single agent, CXD101 caused modest inhibition of tumour growth. In contrast, when administered in combination with anti-PD1 or anti-CTLA4, synergistic anti-tumour activity was observed at well tolerated doses.The CAROSELL clinical trial is testing the effect of CXD101 with nivolumab in MSS colorectal cancer, with the hypothesis that this combination will re-engage recognition of tumours by the immune system.
Trial design
The selected study population were patients with advanced or metastatic MSS CRC, previously threated with at least two lines of therapy; and ECOG PS 0, 1, or 2. A total of 5 UK investigators are contributing subjects to the study, the first of which was treated in July 2018. The design began with a Phase Ib variable dose safety run-in (n = 9). No dose-limiting toxicities were observed, and CXD101 20mg bid in combination with nivolumab 240mg was selected as the Phase II treatment.The primary objective of the Phase II element is to assess immune Disease Control Rate, as determined by CT scan tumour measurements (iRECIST), following a Simon 2-Stage statistical approach. Secondary objectives are to determine 20-week immune-related progression-free survival; overall survival; immune Objective Response Rate, and safety. The CAROSELL Study will recruit a total of 55 subjects.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Celleron Therapeutics Ltd.
Funding
Celleron Therapeutics Ltd.
Disclosure
S. Cook: Shareholder / Stockholder / Stock options, Full / Part-time employment: Celleron therapeutics. N. la Thangue: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Celleron therapeutics. D.J. Kerr: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Celleron therapeutics. All other authors have declared no conflicts of interest.
Resources from the same session
4842 - The analysis of genomic signatures of head and body/tail of pancreatic cancer in Chinese patients
Presenter: Qi Ling
Session: Poster Display session 2
Resources:
Abstract
4988 - MGMT methylation in metastatic pancreatic cancer (mPAC): a single center experience
Presenter: Monica Niger
Session: Poster Display session 2
Resources:
Abstract
5035 - Advantage of three-dimensional image analysis of pancreatic cancer using computed tomography
Presenter: Seung Bae Yoon
Session: Poster Display session 2
Resources:
Abstract
1465 - Phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) with S-1 in patients with stage IV pancreatic cancer.
Presenter: Susumu Hijioka
Session: Poster Display session 2
Resources:
Abstract
1982 - Impact of anatomic site of biliary tract tumour origin and conditional probability of survival (CS): results from 15 prospective advanced first-line clinical trial
Presenter: Mairead McNamara
Session: Poster Display session 2
Resources:
Abstract
2244 - FOLFOXIRI versus FOLFIRINOX in first-line chemotherapy in patients with advanced pancreatic cancer: a propensity score analysis
Presenter: Angélique Vienot
Session: Poster Display session 2
Resources:
Abstract
4557 - Cellfree tumor-DNA (cfDNA) as a very early predictor of therapeutic outcome in pancreatic ductal adenocarcinoma (PDAC)
Presenter: Sabine Payr
Session: Poster Display session 2
Resources:
Abstract
4406 - Comprehensive genomic profiling (CGP) of gall bladder adenocarcinoma (GBAC) in patients from distinct ancestral populations
Presenter: Milind Javle
Session: Poster Display session 2
Resources:
Abstract
4283 - Phase II Monotherapy Efficacy of Cancer Metabolism Targeting SM-88 in Heavily Pre-Treated PDAC Patients.
Presenter: Allyson Ocean
Session: Poster Display session 2
Resources:
Abstract
2078 - Comprehensive genomic profiling and clinical outcomes in patients (pts) with fibroblast growth factor receptor rearrangement-positive (FGFR2+) cholangiocarcinoma (CCA) treated with pemigatinib in the fight-202 trial
Presenter: Antoine Hollebecque
Session: Poster Display session 2
Resources:
Abstract