Prof Chan Cheah

Covering new research into the BTK inhibitor TG-1701 in CLL, Professor Chan Cheah haematologist and lymphoma lead at Sir Charles Gairdner Hospital  in WA presented updated results at ASCO 2021 of the agent as monotherapy and in combination with ublituximab and umbralisib (U2) in patients with B-cell malignancies.

Addressing delegates in the virtual session, Professor Cheah said the combination is highly active in treatment-naive and relapsed/refractory CLL with each demonstrating superiority over standard chemoimmunotherapy.

While the phase I study initially evaluated dose escalation of oral TG-1701 once a day continuously administered in 28-day cycles (100, 200, 300, and 400 mg) in patients with R/R CLL and lymphoma, select dose levels of TG-1701 monotherapy were expanded in CLL, MCL and Waldenström’s once the safety profile of the therapy was identified, Professor Cheah explains.

Reporting on findings from 123 patients up to February this year Professor Cheah said TG-1701 exhibits an ‘encouraging safety and efficacy profile.’ Meanwhile the combination of 1701+U2 has been well tolerated and dose escalation continues with the combination showing enhanced depth of response over TG-1701 monotherapy.

The maximum tolerated dose for monotherapy was not reached at 400 mg and demonstrating near 100% saturation of the BTK at all dose levels studied, he said.

Treatment emergent adverse events (TEAE) of clinical interest included atrial fibrillation (AF 4.0% of pts, G ≥3 in 1 case), G ≥3 hypertension (2.4%), and bleeding events (18.7%, all G1-2). No cases of ventricular tachyarrhythmia were reported.

Adverse events leading to TG-1701 dose reduction occurred in 6.5% of patients, while adverse events leading to treatment discontinuation occurred in 1.6% of patients, of which AF and COVID-19 were cited.

Read more.