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
3716 - Prognostic factors for predicting early recurrence within the first year of surgery in pancreatic ductal adenocarcinoma
Presenter: Naru Kim
Session: Poster Display session 2
Resources:
Abstract
3947 - Integrated population pharmacokinetic modelling of liposomal irinotecan in patients with various tumour types, including untreated metastatic pancreatic cancer (mPC)
Presenter: Teresa Macarulla
Session: Poster Display session 2
Resources:
Abstract
2880 - Expression of long noncoding RNA and clinical outcomes of pancreatic cancer patients who received adjuvant chemotherapy by S-1 or GEM after curative resection.
Presenter: Mariko Kamiya
Session: Poster Display session 2
Resources:
Abstract
5029 - POLO: Time to treatment discontinuation and subsequent therapies following maintenance olaparib for patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC)
Presenter: Eric Van Cutsem
Session: Poster Display session 2
Resources:
Abstract
4730 - Diagnostic Value of Digital Multiplexed Detection of Single Nucleotide Variants in Pancreatic Cancer Specimens Collected by Endoscopic Ultrasound Fine-Needle Aspiration
Presenter: Irina Cazacu
Session: Poster Display session 2
Resources:
Abstract
3303 - Phase I/II study of LDE225 in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer
Presenter: Esther Pijnappel
Session: Poster Display session 2
Resources:
Abstract
2009 - Efficacy of platinum-containing chemotherapy and prognosis of pancreatic cancer patients with homologous recombination deficiency: meta-analysis of published clinical studies
Presenter: Elizeveta Polyanskaya
Session: Poster Display session 2
Resources:
Abstract
2164 - Plasmatic CXCL8 is a marker for TGFß-activated kinase 1 (TAK1) activation which may predict resistance to nanoliposomal irinotecan (nal-IRI) in gemcitabine-refractory pancreatic cancer (PC) patients
Presenter: Valeria Merz
Session: Poster Display session 2
Resources:
Abstract
2529 - A protein level signature of four selected genes associated with survival outcomes of patients with pancreatic ductal adenocarcinoma
Presenter: Jie Hua
Session: Poster Display session 2
Resources:
Abstract
4947 - Pre-treatment serum 25-hydroxyvitamin D levels and survival in a Danish cohort of patients with pancreatic cancer
Presenter: Louise Rasmussen
Session: Poster Display session 2
Resources:
Abstract