PMID- 34417162
OWN - NLM
STAT- MEDLINE
DCOM- 20220407
LR  - 20220407
IS  - 2152-2669 (Electronic)
IS  - 2152-2669 (Linking)
VI  - 21
IP  - 12
DP  - 2021 Dec
TI  - A Phase 2 Study of PNT2258 for Treatment of Relapsed or Refractory B-Cell 
      Malignancies.
PG  - 823-830
LID - S2152-2650(21)00298-6 [pii]
LID - 10.1016/j.clml.2021.07.016 [doi]
AB  - 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.
CI  - Copyright (c) 2021. Published by Elsevier Inc.
FAU - Harb, Wael
AU  - Harb W
AD  - Horizon Oncology Center, Lafayette, IA.
FAU - Lakhani, Nehal J
AU  - Lakhani NJ
AD  - Mercy Health St. Mary's, Grand Rapids, MI.
FAU - Messmann, Richard
AU  - Messmann R
AD  - ProNAi Therapeutics, Inc., Vancouver, BC, Canada.
FAU - Klencke, Barbara
AU  - Klencke B
AD  - Sierra Oncology, Inc. (formerly ProNAi Therapeutics, Inc.), Vancouver, BC, 
      Canada. Electronic address: bklencke@sierraoncology.com.
FAU - Al-Katib, Ayad M
AU  - Al-Katib AM
AD  - Wayne State University, Detroit, MI.
LA  - eng
SI  - ClinicalTrials.gov/NCT01733238
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210723
PL  - United States
TA  - Clin Lymphoma Myeloma Leuk
JT  - Clinical lymphoma, myeloma & leukemia
JID - 101525386
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (PNT100)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Leukemia, Lymphocytic, Chronic, B-Cell/pathology
MH  - *Lymphoma, Follicular
MH  - *Lymphoma, Large B-Cell, Diffuse/pathology
MH  - Oligodeoxyribonucleotides
MH  - Treatment Outcome
OTO - NOTNLM
OT  - B-cell lymphoma
OT  - BCL2
OT  - DLBCL
OT  - Oligonucleotide therapy
EDAT- 2021/08/22 06:00
MHDA- 2022/04/08 06:00
CRDT- 2021/08/21 05:32
PHST- 2021/04/12 00:00 [received]
PHST- 2021/07/06 00:00 [revised]
PHST- 2021/07/16 00:00 [accepted]
PHST- 2021/08/22 06:00 [pubmed]
PHST- 2022/04/08 06:00 [medline]
PHST- 2021/08/21 05:32 [entrez]
AID - S2152-2650(21)00298-6 [pii]
AID - 10.1016/j.clml.2021.07.016 [doi]
PST - ppublish
SO  - Clin Lymphoma Myeloma Leuk. 2021 Dec;21(12):823-830. doi: 
      10.1016/j.clml.2021.07.016. Epub 2021 Jul 23.