| General information |
| Database: | DB00681 |
| Objective: | Maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamics were assessed in thisphase 1 study of PNT2258, a BCL2targeted liposomal formulation of a 24base DNA oligonucleotide called PNT100. |
| Authors: | Molife LR, et al |
| Title: | a phase 1 study of the BCL2targeted deoxyribonucleic acid inhibitor (DNAi) PNT2258 in patients with advanced solid tumors. |
| Journal: | J Hematol Oncol. |
| Year: | 2014 |
| PMID: | 24297683 |
| Trial Design |
| Clinical Trial Id: | NCT01191775 |
| Agent: | PNT2258
|
| Target: | mRNA of BCL2
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I study |
| Key Patients Feature: | The study population included only patients with metastatic solid tumors that had exhausted standard therapeuticoptions; were age more than and equal to 18 years; and had Eastern Cooperative Oncology Group performance status less than and equal to 2 with adequatebone marrow, hepatic, and renal function. As this was apilot dose finding and toxicitycharacterizationphase 1study, preidentification of patients on the basis of theirexisting BCL2 tumor status was not a requirement forstudy participation. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm, |
| Treatment Info: | Patients with malignant solid tumors were assigned sequentially to one of ten doseescalation cohorts of PNT2258 at 1, 2, 4, 8, 16, 32, 64, 85, 113, and 150 mg/m(2) administered intravenously on days 1 through 5 of each 21day cycle. Pharmacokinetics were determined on days 1 and 5 of the first cycle. Lymphocyte and platelets concentrations were measured for evidence of BCL2targeted effect. CT scans were used to identify radiologic evidence of antitumor effect. |
| Primary End Point: | MTD, DLTs, tumor response and toxicity |
| Secondary End Point: | NA |
| Patients Number: | 22 |
| Trial Results |
| DLT_MTD: | the maximum tolerated dose for PNT2258 was not reached. Doselimiting toxicity, manifesting as a transient increase in aspartate aminotransferase, occurred at 150 mg/m(2), the highest dose tested |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common AEs were fatigue (8 events in 7 subjects; 8/79, 10.1 %; grade range 1-2) and infusion reaction manifesting as back or flank pain (6 events in 4 subjects; 6/79; 7.6 %; grade range 2-3). |
| Conclusions: | PNT2258 was safe and well tolerated at the doses tested up to 150mg/m(2). Exposure to PNT2258 resulted in clinically manageable decreases in lymphocyte and platelet concentrations. |