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A Phase 2 Study of PNT2258 for Treatment of Relapsed or Refractory B-Cell Malignancies
Wael Harb1, Nehal J Lakhani2, Richard Messmann3
1Horizon Oncology Center, Lafayette, IA.
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/m2 on Days 1 to 5 of a 21-day cycle for up to 8 cycles, followed by 100 mg/m2 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.
Insights
PNT2258 demonstrated significant antitumor activity in patients with relapsed/refractory B-cell malignancies. This DNA oligonucleotide therapy showed a 53.8% overall response rate with a favorable safety profile.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- PNT2258 is a DNA oligonucleotide targeting the BCL2 gene's regulatory region.
- BCL2 gene dysregulation is common in certain cancers.
- PNT2258 aims to suppress BCL2 transcription for anticancer effects.
Purpose of the Study:
- Evaluate the antitumor activity and safety of PNT2258.
- Investigate PNT2258 as monotherapy in relapsed/refractory B-cell malignancies.
- Assess response rates, duration of response, and adverse events.
Main Methods:
- Phase 2, multicenter, nonrandomized, open-label study.
- 13 participants with follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, or chronic lymphocytic leukemia.
- Intravenous PNT2258 administration at specified doses and cycles.
Main Results:
- Overall response rate of 53.8% (7/13).
- Median duration of response of 23.4 months.
- Disease control rate of 84.6% with acceptable safety profile; no deaths observed.
Conclusions:
- PNT2258 monotherapy shows clinically meaningful and durable activity.
- The safety profile of PNT2258 is acceptable in this patient population.
- PNT2258 represents a potential treatment option for relapsed/refractory B-cell malignancies.
