ProNAi Therapeutics, Inc, a clinical stage oncology company that develops therapeutic drugs based on its proprietary DNA interference (DNAi) technology platform, is currently enrolling patients in Wolverine, a clinical trial evaluating PNT2258’s efficacy and safety in treating people with relapsed or refractory (r/r) diffuse large B-cell lymphoma.
The clinical trial (NCT02226965) is a Phase 2 investigation of PNT2258’s anti-tumor activity and safety. The multicenter, open label and nonrandomized study has overall response rate as its primary outcome measure. Secondary outcome measures include the disease control rate, time to response, progression-free survival, and safety. A dose of 120 mg/m2 of the drug will be administered on days one through five on a 21-day cycle, for a total of eight treatment cycles. At the end of the eight cycles, certain participants can continue receiving PNT2258 therapy at a dose of 100 mg/m2 on days one through four of a 28-day cycle. Treatment continuation at any phase is dependent on the non-occurrence of disease progression, toxicity, and demonstrated benefit, among other factors.
PNT2258, the company’s lead product candidate, is a formulation of single-stranded 24-base DNAi oligonucleotide, known as PNT100, in the SMARTICLES LNP capsules. The oligonucleotide targets and interferes with the expression of the oncogene BCL2, known to be dysregulated in many types of cancer and to provide cancer cells with the ability to resist apoptosis, the natural death of aged and damaged cells. BCL2 expression is also associated with poor prognosis and chemotherapy resistance. Based on previous preliminary evidence of efficacy and tolerability, from a Phase 1 safety trial in patients with relapsed or refractory solid tumors and a Phase 2 trial in patients with relapsed or refractory NHL, the company is now clinically developing PNT2258 as a multi-faceted drug to act across many oncology indications.
Eligibility criteria includes confirmed diffuse large B-cell lymphoma that is refractory to prior therapy or relapsed after prior therapy, with previous therapy having included CD20-targeted therapy (for example, rituximab), alkylating agent (such as cyclophosphomide) and steroids (except for steroid intolerant patients). Researchers expect to enroll 61 people and estimate the study will be completed in October 2018.
More information on the trial, taking place at 28 centers across the United States and in Puerto Rico, is available through this link.