| Autor: |
Iyer SP; The University of Texas MD Anderson Cancer Center, TX. SPIyer@mdanderson.org., Huen A; The University of Texas MD Anderson Cancer Center, TX., Ai WZ; Helen Diller Family Comprehensive Cancer Center, CA., Jagadeesh D; Taussig Cancer Institute, OH., Lechowicz MJ; Winship Cancer Institute, GA., Okada C; Oregon Health and Science University, OR., Feldman TA; John Theurer Cancer Center at Hackensack University Medical Center, NJ., Ghione P; Roswell Park Comprehensive Cancer Center, NY., Alderuccio JP; Sylvester Comprehensive Cancer Center, FL., Champion R; Norton Cancer Institute, KY., Kim SH; Rush University Medical Center, IL., Mohrbacher A; University of Southern California, CA., Routhu KV; Rhizen Pharmaceuticals AG., Basel., Barde P; Rhizen Pharmaceuticals AG., Basel., Nair AM; Rhizen Pharmaceuticals AG., Basel., Haverkos BM; University of Colorado Cancer Center, CO. |
| Jazyk: |
angličtina |
| Zdroj: |
Haematologica [Haematologica] 2024 Jan 01; Vol. 109 (1), pp. 209-219. Date of Electronic Publication: 2024 Jan 01. |
| DOI: |
10.3324/haematol.2022.281875 |
| Abstrakt: |
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 twice-daily and intravenous romidepsin administered on days 1, 8 and 15 in 28-day cycles in adults with relapsed/refractory TCL. Phase I/dose escalation determined the maximum tolerated dose (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 was identified. Hence, the recommended doses for dose expansion were tenalisib 800 mg twice daily orally, and romidepsin 14 mg/m2 intravenous. Overall treatment-emergent adverse events 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 treatment-emergent adverse events. The overall objective response rate in evaluable patients was 63.0% (peripheral TCL: 75% and cutaneous TCL: 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. Co-administration 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 (clinicaltrials gov. Identifier: NCT03770000). |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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