Evolving chemotherapeutics

Independent Data Safety Monitor Recommends Deflexifol™ Dose Escalation after Review of Promising Clinical Results

FivepHusion today announces important progress in its ongoing FP101A phase 1b/2a dose-escalation clinical study of Deflexifol™ in patients with advanced solid tumours:

  • Deflexifol™ is an optimised all-in-one formulation of the chemotherapeutic agents 5-fluorouracil (5-FU) and leucovorin (LV) for the treatment of solid tumours
  • The ongoing FP101A phase 1b/2a clinical study is designed to confirm the pharmacokinetics (PK), safety, tolerability and maximum tolerated dose (MTD) of Deflexifol™
  • Fourteen end stage solid tumour patients have been treated in FP101A to date, with a very favourable safety and tolerability profile reported. Patients that were eligible to continue treatment after the designated study treatment phase elected to do so, which is indicative of the enhanced safety and tolerability of Deflexifol™ at all doses investigated to date
  • Current PK data confirms the bioequivalence of 5-FU and LV co-formulated in Deflexifol™ to standard of care (SOC) individual formulations of the drugs; positioning Deflexifol™ for expedited regulatory routes in major markets.
  • A review of efficacy data, a secondary trial endpoint, has demonstrated that Deflexifol™ treatment led to stable disease in the majority of evaluable patients
  • The trial Independent Data Safety Monitor has reviewed the current clinical data set, and recommended Deflexifol™ dose escalation to Dose Level 4, the highest dose (525mg/m2 bolus + 3800mg/m2 infusion, administering 54% more 5-FU than SOC)
  • The FP101A data reaffirms the superior safety and tolerability of Deflexifol™ over SOC 5-FU formulations in end stage solid tumour patients, as observed in the previously completed forty patient phase 1b/2a clinical study, FP101.

FivepHusion is developing Deflexifol™, an optimised all-in-one formulation of the chemotherapeutic agent 5-FU and its biomodulator LV for the treatment of solid tumours. Deflexifol™ is specifically formulated to facilitate for the first time, the simultaneous administration of both agents at a physiological pH. This novel co-formulation offers significantly reduced toxicity, enhanced safety, and improved tolerability of greater 5-FU doses compared to SOC formulations. In FP101, an original forty patient phase 1b/2a clinical study in end stage solid tumour patients[1], Deflexifol™ demonstrated superior safety and tolerability at much higher doses of 5-FU than are typically given in the standard of care. Higher doses of 5-FU correlate with improved response and better survival of metastatic colorectal cancer patients[2], whilst the biomodulator LV potentiates 5-FU cytotoxicity to kill cancer cells[3]. Current formulations of 5-FU and LV suffer from limitations in their safety, tolerability, effectiveness and pharmacological compatibility. These shortcomings contribute to limited treatment response rates, unpleasant side effects and toxicities, and the reduced quality of life experienced by cancer patients. Deflexifol™ has been designed to address these limitations.

Deflexifol™ is currently being investigated in FP101A (ACTRN12619001533189, link), an ongoing phase 1b/2a dose ranging clinical study designed to confirm the pharmacokinetics, safety, tolerability and maximum tolerated dose of Deflexifol™. The drug is administered in a traditional 3+3 trial design to end stage solid tumour patients as a bolus followed by a 46-hour infusion once every two week cycle, for a total of four cycles of treatment. The study is being performed at Southern Medical Day Care Centre link, and is led by Principal Investigator, Associate Professor Daniel Brungs. End stage patients recruited into this study have a range of solid tumours, including metastatic colorectal cancer, breast, gastric and pancreatic cancers, and are typically heavily pre-treated, many patients having previously failed SOC 5-FU therapy as part of multiple treatment regimens.

To date, a total of fourteen patients have been recruited into FP101A, investigating Deflexifol™ at increasing dose levels. Deflexifol™ has demonstrated favourable safety and tolerability at all doses, including at Dose Level 3 (525mg/m2 bolus + 3400mg/m2 infusional dose), delivering ~40% more 5-FU than is typically given in SOC clinical practice[4]. The Independent Data Safety Monitor has now reviewed the accumulated patient data and recommended that new patients be recruited into the study at Dose Level 4, the highest dose in this study, delivering a 525mg/m2 bolus followed by a 3800mg/m2 infusional dose of Deflexifol™, or the equivalent of ~54% more 5-FU than SOC therapy.

Pharmacokinetic analyses of 5-FU and LV delivered by Deflexifol™ have confirmed their pharmacology is typical of these agents delivered independently by SOC formulations. This data supports the bioequivalence of 5-FU and LV formulated in Deflexifol™, allowing for potentially accelerated and de-risked regulatory routes via the US FDA, European Medicines Agency and other global regulatory agencies.

A review of tumour responses at each dose has confirmed that the majority of evaluable patients receiving Deflexifol™ have recorded stable disease during the designated study treatment phase. Patients that were eligible to continue treatment after receiving the minimum of four cycles required by the study protocol elected to do so, with one patient having received up to thirteen cycles of treatment. The continued participation of these patients in the trial further supports the increased safety and tolerability of Deflexifol™ treatment, highlighting its potential to provide an improved quality of life for cancer patients than is typically experienced with current chemotherapy formulations.

Associate Professor Daniel Brungs, Southern Day Care Clinic, Principal Investigator for FP101A commented “The FP101A clinical trial continues to confirm the safety and tolerability of Deflexifol at high doses of 5-FU in end stage solid tumour patients. Pleasingly, we have also observed objective responses to this therapy. We are now planning to investigate the safety and tolerability of Deflexifol at Dose Level 4, the highest and final dose level in this trial.”

Dr Christian Toouli, CEO and Managing Director of FivepHusion said “We are delighted with the progress of this important clinical study. FP101A builds on the existing clinical experience with Deflexifol in our original FP101 phase 1b/2a study, with a cumulative total of 54 patients now treated. Deflexifol continues to demonstrate its potential as a promising new chemotherapy for the treatment of metastatic colorectal cancer and other solid tumours.” FivepHusion is aiming to complete recruitment of the FP101A clinical study in the coming months, with the goal of confirming the understanding of the pharmacokinetics, safety and MTD of Deflexifol™. In consultation with its recently announced independent, expert Clinical Advisory Board, the company is currently refining the design of a global phase III registration trial in 1st line unresectable metastatic colorectal cancer to ensure regulatory approval in major markets and support subsequent clinical uptake as a replacement for sub-optimal SOC 5-FU/LV formulations. FivepHusion intends to finalise the phase III trial design during H1 2022, followed by consultations with global regulatory agencies, including the FDA and EMA, to facilitate initiation of the global registration study.

[1] Clingan et al., 2019, Asia-Pac J Clin Oncol.,1-7;

[2] Saif et al.,2009, J Natl Cancer Inst., 101:1543-1552;

[3] Longley et al. 2003, Nature Reviews Cancer 3(5):330-338.

[4] www.eviq.org.au