Abstract 2012
Background
5-fluorouracil (5-FU) in combination with the folate Leucovorin (LV) has been the cornerstone in the treatment of colorectal cancer (CRC) for decades. All folates currently approved for use in the clinical setting need to be metabolically activated to [6R] 5,10-methylenetetrahydrofolic acid ([6R]-MTHF), which is the active thymidylate synthase co-substrate that potentiates the effect of 5-FU. Arfolitixorin does not need multi step metabolic activation like currently available folates. It is therefore hypothesized that the administration of arfolitixorin will result in higher, and less individual variability, intracellular concentrations of the active thymidylate synthase co-substrate [6R]-MTHF in all patients compared to LV administration.
Trial design
Primary endpoint ORR by Blinded Independent Central Review (BICR) Key secondary endpoints Progression Free Survival (PFS) Duration of Response (DoR) Secondary endpoints Overall Survival (OS) Quality of Life (QoL) Safety and Tolerability Patients undergoing curative metastasis resection Study Design This is a randomized, multicenter, parallel-group, Phase III study to compare the efficacy of arfolitixorin versus LV in patients with mCRC treated with 5-FU, oxaliplatin, and bevacizumab. Patients will be randomized in a 1:1 ratio to either the investigational arm or the comparator arm. The study target is to randomize 440 patients in 18 months. An adaptive study design includes the possibility to increase the sample size to 660 patients as determined by the DSMB during the interim analysis to be conducted after 330 patients have conducted their 16 weeks scan. Key inclusion criteria: Adults > 18 years of age Colorectal adenocarcinoma verified by biopsy Non-resectable mCRC No prior treatment for first line mCRC ECOG performance status 0 or 1 Key exclusion criteria: Malignant tumors other than colorectal adenocarcinomas Less than 6 months since last anti-cancer treatment DPD deficiency Clinically significant cardiovascular disease Central nervous system metastases Study Countries Australia, Austria, Canada, France, Germany, Greece, Spain, Sweden and USA FPI: December 18, 2018.
Clinical trial identification
NCT03750786; 2017-004154-41.
Editorial acknowledgement
Legal entity responsible for the study
Isofol Medical AB.
Funding
Isofol Medical AB.
Disclosure
J. Tabernero: Advisory / Consultancy: Array Biopharma; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BeiGene; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Chugai; Advisory / Consultancy: Genetech Inc; Advisory / Consultancy: Genemab A/S; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Imugene Limited; Advisory / Consultancy: Inflection Biosciences Limited; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Kura Oncology; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Menarini; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Merrimack; Advisory / Consultancy: Merus; Advisory / Consultancy: Molecular Partners; Advisory / Consultancy: Novartis. G. Prager: Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Lilly; Advisory / Consultancy: Servier; Advisory / Consultancy: Taiho; Advisory / Consultancy: Bayer; Advisory / Consultancy: Halozyme; Advisory / Consultancy: BMS; Advisory / Consultancy: Cellgene; Advisory / Consultancy: Shire. S. Stintzing: Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Roche; Advisory / Consultancy: Merck; Advisory / Consultancy: Lilly; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Taiho; Advisory / Consultancy: Takeda; Advisory / Consultancy: Servier. H.J. Lenz: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Boehringer Ingelheim. H.P. Nygren: Shareholder / Stockholder / Stock options: Oncopeptides; Research grant / Funding (institution), Licensing / Royalties: Respos Pharma. C. Papadimitriou: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Research grant / Funding (self): BMS; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Genesis; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Merck.
Resources from the same session
3266 - Morphology of tumor-associated macrophages dictates the prognosis of patients with colorectal liver metastases.
Presenter: Matteo Donadon
Session: Poster Display session 2
Resources:
Abstract
1694 - Pembrolizumab (pembro) Plus mFOLFOX or FOLFIRI in Patients With Metastatic Colorectal Cancer (mCRC): KEYNOTE-651 Cohorts B and D
Presenter: Richard Kim
Session: Poster Display session 2
Resources:
Abstract
908 - Romidepsin (FK228) Regulates the Expression of the Immune Checkpoint Ligand PD-L1 and Exerts Synergistic Anti-Tumor Activity with an Anti-PD-1 Antibody in Colon Cancer
Presenter: Hui Li
Session: Poster Display session 2
Resources:
Abstract
3127 - Prognostic significance of circulating regulatory T lymphocytes (Tregs) in patients with metastatic colorectal cancer (mCRC) under treatment with first line chemotherapy.
Presenter: Zafeiris Zafeiriou
Session: Poster Display session 2
Resources:
Abstract
5416 - The SAFFO study: Sex-related prognostic role And cut-oFf deFinition of monocyte-to-lymphocyte ratio (MLR) in metastatic colOrectal cancer
Presenter: Camilla Lisanti
Session: Poster Display session 2
Resources:
Abstract
2518 - SPICE, a phase I study of enadenotucirev in combination with nivolumab in tumors of epithelial origin: analysis of the metastatic colorectal cancer patients in the dose escalation phase
Presenter: Marwan Fakih
Session: Poster Display session 2
Resources:
Abstract
4000 - Phase 1/2 study with CXCL12 inhibitor NOX-A12 and pembrolizumab in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer
Presenter: Niels Halama
Session: Poster Display session 2
Resources:
Abstract
2223 - Microsatellite Instability Status in Metastatic Colorectal Cancer and Effect of Immune Checkpoint Inhibitors on Survival in MSI-High Metastatic Colorectal Cancer
Presenter: Wataru Okamoto
Session: Poster Display session 2
Resources:
Abstract
2569 - Phase II trial of Trametinib (T) and Panitumumab (Pmab) in RAS/RAF wild type (wt) metastatic colorectal cancer (mCRC)
Presenter: Kanan Alshammari
Session: Poster Display session 2
Resources:
Abstract
5402 - Microsatellite instability and immunogenicity in colorectal cancer – do resident memory Tcells (Trm) play a role in colorectal cancer
Presenter: Wei Toh
Session: Poster Display session 2
Resources:
Abstract