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
3191 - The efficacy and safety of lenvatinib in patients who did not meet the inclusion criteria of the phase 3 trial (REFLECT trial) and those with BCLC Stage B hepatocellular carcinoma - A nationwide multicenter study in Japan-
Presenter: Azusa Sakamoto
Session: Poster Display session 2
Resources:
Abstract
1529 - Prognostic and predictive value of baseline alpha-fetoprotein (AFP) in patients with advanced hepatocellular carcinoma (HCC) treated with ramucirumab from two phase 3 studies (REACH, REACH-2)
Presenter: Andrew Zhu
Session: Poster Display session 2
Resources:
Abstract
2767 - Effect of second-line cabozantinib on health states for patients with advanced hepatocellular carcinoma (aHCC) after sorafenib: QTWiST analysis from the CELESTIAL study
Presenter: Nicholas Freemantle
Session: Poster Display session 2
Resources:
Abstract
2150 - Alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (HCC) in the phase 3 RESORCE trial
Presenter: Jordi Bruix
Session: Poster Display session 2
Resources:
Abstract
3437 - Phase I/II trial of NBTXR3 activated by SBRT in patients with hepatocellular carcinoma or liver metastasis
Presenter: Marc Pracht
Session: Poster Display session 2
Resources:
Abstract
1758 - Efficacy and safety of ramucirumab (RAM) for advanced hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) following first-line sorafenib across age subgroups in two global phase 3 trials (REACH and REACH-2)
Presenter: Masatoshi Kudo
Session: Poster Display session 2
Resources:
Abstract
1192 - Ramucirumab in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha fetoprotein (AFP): An exposure–response analysis
Presenter: Josep Llovet
Session: Poster Display session 2
Resources:
Abstract
1600 - Outcomes of Hepatocellular Carcinoma (HCC) Patients Treated with Nivolumab: The Mount Sinai Hospital Experience.
Presenter: Sirish Dharmapuri
Session: Poster Display session 2
Resources:
Abstract
2364 - Pembrolizumab vs Chemotherapy in Patients With Advanced/Metastatic Adenocarcinoma (AC) or Squamous Cell Carcinoma (SCC) of the Esophagus as Second-Line Therapy: Analysis of the Chinese Subgroup in KEYNOTE-181
Presenter: Jia Chen
Session: Poster Display session 2
Resources:
Abstract
1933 - A national comparative effectiveness study to assess definitive chemoradiation regimens in proximal oesophageal squamous cell cancer
Presenter: Judith de Vos-Geelen
Session: Poster Display session 2
Resources:
Abstract