ODM-207 – First-in-human Phase 1 study of BET inhibitor for solid tumour patients

RUCHITA KARMAKAR, AMITY UNIVERSITY KOLKATA

BET (Bromodomain and extra terminal domain) proteins are described to be epigenetic and anti-cancer drug targets. This was the first-in-human study that judged the pharmacokinetics and prior activity of ODM-20, the inhibitor of BET in patients having solid tumours. 

The main objective was to determine the tolerability, dose-limiting toxicities (DLT), and also the maximum tolerated dose (MTD) of the patients subjected to solid tumours. The second objective is to exemplify the pharmacokinetics of the inhibitor, mainly to assess the effects of food bioavailability and also to cause the preliminary verification of the anti-tumour activity. 

The study design consisted of two parts:

 1) The escalation of dose to the patients having advanced solid tumours 

2)  Rating of the effect of food on the bioavailability 

For the patients having an advanced solid tumour, a single dose was given with the accelerated titration procedure, in the very first division, which involved the comparison of the pharmacokinetic parameters in the first division of the patients to check whether it reached the targeted range or otherwise. If not, the dose was given in a 3+3 schedule. The food effect involved the single accelerated dose after the washout period ODM-207 after breakfast. 

About thirty-five patients were treated with ODM-207, some common AE’s were observed, nevertheless, ODM-207 shows great increasing exposure in the dose, and was safe at the doses to 2mg/kg but had a tapered therapeutic window. 

The registration number for the clinical trial being NCT03035591.

Also read: Blocking autophagy to prevent old age organ decline? Find out

Citation : Malaka Ameratunga , Irene Brana , Petri Bono , Ruth Plummer , John Aspegren , Timo Korjamo , Amir Snapir  , Sophie Postel-Vinay and JohannS de Bono . 

Site: https://www.nature.com/articles/s41416-020-01077-z

For more updates: https://bioxone.in