Early Australian research on a new BTK inhibitor is showing promise in patients with relapsed/refractory B-cell malignancies both as a single agent and in a novel triple combination with two other new drugs.
Speaking to the limbic at ASH 2019, lead investigator Associate Professor Chan Cheah said the oral BTK inhibitor TG-1701 had previously been shown to have superior selectivity for BTK compared to ibrutinib.
The other agents, not yet licensed in Australia, were a highly active anti-CD20 monoclonal antibody -ublituximab – and PI3K-delta and a casein kinase 1-epsilon inhibitor, umbrilisib.
Associate Professor Cheah said umbrilisib was similar to idelalisib, which although approved in Australia was not used much due to its side effect profile.
“Umbrilisib seems to be different – you don’t see so many of those side effects and so you don’t get liver inflammation, you don’t get bad inflammation of the gut. It’s much better tolerated.”
The phase 1 trial enrolled patients with various B-cell lymphomas including Waldenstrom’s macroglobulinemia, CLL, follicular lymphoma and DLBCL.
“… and we have seen responses across the board. So it looks encouraging,” he said.
Partial responses were observed with TG-1701 monotherapy as well as partial and early complete responses to the combination treatment.
TG-1701 showed clinical and pharmacodynamic activity from 100mg to 400mg and dose escalation studies of the triple combination and expansion cohorts in CLL, Waldenstrom’s and mantle cell lymphoma were ongoing.
Associate Professor Cheah, from Sir Charles Gairdner Hospital and the University of Western Australia, said the study commenced with four Australian sites in Melbourne, Adelaide and Perth and has since opened up to additional trial sites in Poland.
“The drug represents a new BTK inhibitor which is active and well tolerated and, more importantly, this research is exploring a novel combination strategy in patients with relapsed/refractory B cell malignancies.”