| Autor: |
Amer M. Zeidan, Rachel J. Cook, Rodolfo Bordoni, James R. Berenson, William J. Edenfield, Sanjay Mohan, Gongfu Zhou, Ekaterine Asatiani, Nithya Srinivas, Michael R. Savona |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Clinical lymphoma, myelomaleukemia. 22(7) |
| ISSN: |
2152-2669 |
| Popis: |
The Janus kinase (JAK)/signal transducers and activators of transcription pathway has been implicated in the pathogenesis and progression of various hematologic malignancies. JAK1-regulated cytokines stimulate proliferation and growth of malignant cells and resistance to certain therapies.This phase 1/2 study evaluated 2 oral, novel JAK1 inhibitors (INCB052793 and itacitinib) in advanced hematologic malignancies. Phase 1a assessed dose escalation and expansion of INCB052793 monotherapy. Phase 1b evaluated INCB052793 plus standard therapy in relapsed/refractory multiple myeloma, acute myeloid leukemia (AML), or myelodysplastic syndrome (MDS). Phase 2 evaluated INCB052793 or itacitinib plus azacitidine in DNA methyltransferase inhibitor (DNMTi)-refractory AML or MDS. Primary endpoints included safety and tolerability for phase 1, and objective response rate for phase 2.Fifty-eight patients were enrolled, all received study treatment and discontinued either treatment or participation in the study. The most common reasons for treatment discontinuation were progressive disease (35.4% and 50.0%) and adverse events (22.9% and 20.0%) for INCB052793 and itacitinib plus azacitidine, respectively. In phase 1, 12 of 39 patients (31%) achieved an objective response; 35 mg once daily was selected as the phase 2 dose. Two patients with DNMTi-refractory disease had an objective response in phase 2. The study was terminated for lack of efficacy.Inhibition of JAK1 with INCB052793 (monotherapy or combination therapy) or itacitinib plus azacitidine did not demonstrate clinically meaningful responses in these patients with hematopoietic malignancies. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect