A Phase 2 Study of PNT2258 for Treatment of Relapsed or Refractory B-Cell Malignancies.

Autor: Harb W; Horizon Oncology Center, Lafayette, IA., Lakhani NJ; Mercy Health St. Mary's, Grand Rapids, MI., Messmann R; ProNAi Therapeutics, Inc., Vancouver, BC, Canada., Klencke B; Sierra Oncology, Inc. (formerly ProNAi Therapeutics, Inc.), Vancouver, BC, Canada. Electronic address: bklencke@sierraoncology.com., Al-Katib AM; Wayne State University, Detroit, MI.
Jazyk: angličtina
Zdroj: Clinical lymphoma, myeloma & leukemia [Clin Lymphoma Myeloma Leuk] 2021 Dec; Vol. 21 (12), pp. 823-830. Date of Electronic Publication: 2021 Jul 23.
DOI: 10.1016/j.clml.2021.07.016
Abstrakt: Background: PNT2258 consists of a native, chemically unmodified, 24-base DNA oligonucleotide designed to target the regulatory region upstream of the BCL2 gene, delivered in a protective liposome. Derangement of BCL2-regulated control mechanisms is a defining characteristic of certain malignancies, and it was hypothesized that the oligonucleotide would promote anticancer activity via suppression of BCL2 transcription.
Methods: PNT2258 was evaluated in this, multicenter, nonrandomized, open-label Phase 2 study in 13 participants with relapsed/refractory B-cell malignancies to investigate potential antitumor activity and safety. Participants with follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, or chronic lymphocytic leukemia received intravenous PNT2258 120 mg/m 2 on Days 1 to 5 of a 21-day cycle for up to 8 cycles, followed by 100 mg/m 2 on Days 1 to 2 of a 28-day cycle until study withdrawal.
Results: All 13 participants were treated with PNT2258 monotherapy and evaluable for response and safety and tolerability. The overall response rate was 53.8% (7/13; 95% confidence interval [CI], 25.1%-80.8%). Median duration of response was 23.4 months (range, 3, 31.5). The disease control rate of participants with stable disease or better was 84.6% (95% CI, 54.6%-98.1%). The most frequently (≥50%) observed adverse events (AEs) were nausea, chills, diarrhea, fatigue, headache, vomiting, and back pain. Hypertension (30.8%) and diarrhea (23.1%) were the most frequent grade ≥3 AEs. No deaths were observed.
Conclusion: Clinically meaningful and durable activity with an acceptable safety profile was observed in participants with relapsed/refractory B-cell malignancies who received single-agent PNT2258.
Trial Registration: NCT01733238, first posted 26-Nov-2012. https://clinicaltrials.gov/ct2/show/NCT01733238.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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