Safety and efficacy of tenalisib in combination with romidepsin in patients with relapsed/refractory T-cell lymphoma: results from a phase I/II open-label multicenter study

Abstract

Tenalisib, a selective phosphoinositide-3-kinase δ/γ, and salt-inducible-kinase-3 inhibitor has shown efficacy and was well-tolerated in patients with T-cell lymphoma (TCL). In vitro studies suggest a synergistic anti-tumor potential for the combination of tenalisib with the histone-deacetylase inhibitor, romidepsin. This multicenter, open-label, phase I/II study was designed to characterize the safety, efficacy and pharmacokinetics of oral tenalisib twicedaily (BID) and intravenous (IV) romidepsin administered on Days 1, 8 and 15 in 28-day cycles in adults with relapsed/refractory TCL. Phase I/dose-escalation determined the MTD/optimal doses of tenalisib and romidepsin. The phase II/dose-expansion assessed the safety and anti-tumor activity of the combination at MTD/optimal dose. Overall, 33 patients were enrolled. In dose-escalation, no dose-limiting toxicity (DLT) was identified. Hence, the recommended doses for dose-expansion were tenalisib 800 mg BID orally, and romidepsin 14 mg/m2 IV. Overall treatment-emergent adverse events (TEAE) of any grade reported in >15% of patients were nausea, thrombocytopenia, increased aspartate aminotransferase, increased alanine aminotransferase, decreased appetite, neutropenia, vomiting, fatigue, anemia, dysgeusia, weight loss, diarrhea, and hypokalemia. Twenty-three patients (69.7%) had related ≥Grade 3 TEAE. The overall objective response rate in evaluable patients was 63.0% (PTCL: 75% and CTCL: 53.3%), with a complete response and partial response of 25.9% and 37.0% respectively. The median duration of response was 5.03 months. Coadministration of tenalisib and romidepsin did not significantly alter the pharmacokinetics of romidepsin. Overall, tenalisib and romidepsin combination demonstrated a favorable safety and efficacy profile supporting its further development for relapsed/refractory TCL.