Table_1_PARC: a phase I/II study evaluating the safety and activity of pegylated recombinant human arginase BCT-100 in relapsed/refractory cancers of .docx (64.03 kB)

Table_1_PARC: a phase I/II study evaluating the safety and activity of pegylated recombinant human arginase BCT-100 in relapsed/refractory cancers of children and young adults.docx

dataset

posted on 2024-01-31, 04:32 authored by Nicola Fenwick, Rebekah Weston, Keith Wheatley, Jodie Hodgson, Lynley Marshall, Martin Elliott, Guy Makin, Antony Ng, Bernadette Brennan, Stephen Lowis, Jenny Adamski, John Paul Kilday, Rachel Cox, Mike Gattens, Andrew Moore, Toby Trahair, Milind Ronghe, Martin Campbell, Helen Campbell, Molly W. Williams, Maria Kirby, Natasha Van Eijkelenburg, Jennifer Keely, Ugo Scarpa, Victoria Stavrou, Livingstone Fultang, Sarah Booth, Paul Cheng, Carmela De Santo, Francis Mussai

Background

The survival for many children with relapsed/refractory cancers remains poor despite advances in therapies. Arginine metabolism plays a key role in the pathophysiology of a number of pediatric cancers. We report the first in child study of a recombinant human arginase, BCT-100, in children with relapsed/refractory hematological, solid or CNS cancers.

Procedure

PARC was a single arm, Phase I/II, international, open label study. BCT-100 was given intravenously over one hour at weekly intervals. The Phase I section utilized a modified 3 + 3 design where escalation/de-escalation was based on both the safety profile and the complete depletion of arginine (defined as adequate arginine depletion; AAD <8μM arginine in the blood after 4 doses of BCT-100). The Phase II section was designed to further evaluate the clinical activity of BCT-100 at the pediatric RP2D determined in the Phase I section, by recruitment of patients with pediatric cancers into 4 individual groups. A primary evaluation of response was conducted at eight weeks with patients continuing to receive treatment until disease progression or unacceptable toxicity.

Results

49 children were recruited globally. The Phase I cohort of the trial established the Recommended Phase II Dose of 1600U/kg iv weekly in children, matching that of adults. BCT-100 was very well tolerated. No responses defined as a CR, CRi or PR were seen in any cohort within the defined 8 week primary evaluation period. However a number of these relapsed/refractory patients experienced prolonged radiological SD.

Conclusion

Arginine depletion is a clinically safe and achievable strategy in children with cancer. The RP2D of BCT-100 in children with relapsed/refractory cancers is established at 1600U/kg intravenously weekly and can lead to sustained disease stability in this hard to treat population.

Clinical trial registration

EudraCT, 2017-002762-44; ISRCTN, 21727048; and ClinicalTrials.gov, NCT03455140.