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
5063 - Does Nutritional Status Affect Treatment Tolarability, Response and Survival in Metastatic Gastric Cancer Patients? Results of Prospective Multicenter Study
Presenter: Senem Karabulut
Session: Poster Display session 2
Resources:
Abstract
2717 - Ramucirumab use in patients with Advanced Gastric Cancer (AGC) or gastro-oesophageal junction (GEJ) adenocarcinoma in Spain: RAMIS observational study
Presenter: Federico Longo Munoz
Session: Poster Display session 2
Resources:
Abstract
3187 - Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor: Exploratory analysis in the patients who were enrolled in JCOG0705/KGCA01 phase III trial (REGATTA) and could continue chemotherapy
Presenter: Takaki Yoshikawa
Session: Poster Display session 2
Resources:
Abstract
4765 - A prospective observational study on the optimal maintenance strategy in HER2-positive advanced gastric cancer treated with trastuzumab based therapy
Presenter: Qian Li
Session: Poster Display session 2
Resources:
Abstract
3500 - Randomised phase 2 trial of first-line docetaxel, carboplatin, capecitabine (CTX) and epirubicin, oxaliplatin, capecitabine (EOX) in advanced esophagogastric adenocarcinoma (SEED)
Presenter: Peter Petersen
Session: Poster Display session 2
Resources:
Abstract
5197 - Ramucirumab in the treatment of refractory metastatic gastric cancer: results from the RamSelGa trial.
Presenter: Alexey Tryakin
Session: Poster Display session 2
Resources:
Abstract
2011 - Regorafenib in combination with Paclitaxel for beyond first-line treatment of advanced esophagogastric cancer (REPEAT): a phase Ib trial with expansion cohort
Presenter: Mohammed Khurshed
Session: Poster Display session 2
Resources:
Abstract
2117 - The relationship between the survival and fixed dosing of S-1 in advanced gastric cancer patients by pooled analysis using individual data from four Japanese randomized phase III trials
Presenter: Wataru Ichikawa
Session: Poster Display session 2
Resources:
Abstract
2669 - A Phase 1b Study of Oraxol in Combination with Ramucirumab in Patients with Gastric or Esophageal Cancers who failed previous chemotherapy
Presenter: Ming Huang Chen
Session: Poster Display session 2
Resources:
Abstract
3240 - Efficacy and safety of trifluridine/tipiracil (FTD/TPI) in European patients with heavily pretreated metastatic gastric cancer (mGC): an analysis of the TAGS study
Presenter: Maria Alsina
Session: Poster Display session 2
Resources:
Abstract