The BCL2 Targeted Deoxyribonucleic Acid Inhibitor (DNAi) PNT2258 Is Active in Patients with Relapsed or Refractory Non-Hodgkin’s Lymphoma

Background: PNT2258 is a 24-base, single-stranded liposome-encapsulated DNA oligonucleotide that hybridizes to regions of the BCL2 gene, modulating its function. As previously reported, PNT2258 demonstrates antitumor activity in patients with advanced-stage NHL. The updated clinical data that are provided in this abstract (as of 07/25/14) now include anti-tumor activity in patients with DLBCL and Richter’s syndrome.

Methods: All patients had CT-measureable, FDG-PET positive disease with progression prior to study entry, and had previously received rituximab and combination cytotoxic chemotherapy. Refractory tumor status or concomitant medical issues precluded the use of additional cytotoxic therapy in all patients included in the study. PNT2258 induction cycles were administered as a 3-hour IV infusion at 120 mg/m² days 1-5 of each 21-day cycle for up to 8 cycles. Response evaluation occurred at the end of cycles 2, 6 and 8. Following induction, patients could receive maintenance dosing at 100 mg/m²days 1-2 of each 28-day cycle until PD.

Results: Thirteen patients (median age 65; 8 males, 5 females; ECOG PS 0/1/2: 3/9/1) received all scheduled doses of PNT2258. Regardless of attribution, there were no cycle 1, grade 3/4 AEs. The most common grade 1/2 AEs in cycle 1 included chills, low-grade fever, transient nausea, and tumor or back pain (n=5 for each). There was no evidence of tumor lysis syndrome, febrile neutropenia or significant GI toxicity. Of 4 patients with DLBCL, including 1 with Richter’s syndrome and 1 with Burkitt-like histology, PFS was 9.2 months, range 5.5-12.3 months as of 7/25/14. Best response data (CR/PR/SD/PD) for the DLBCL group was 2/1/1/0. Additionally, in 5 FL patients, best response was 1/1/3/0. Five patients, including 3 DLBCL and 2 FL remain on study as of 7/25/14 receiving maintenance treatment with PNT2258.

Conclusions: PNT2258 is well tolerated and can be administered over prolonged periods of time. Durable single agent activity was previously reported in patients with FL, and has now been observed in patients with aggressive DLBCL. Studies in DLBCL and Richter’s syndrome are being implemented and updated information will be provided at the time of the meeting. Clinical trial information: NCT01733238.