Rapid Readouts: Interim Analysis Results From the Phase 2 PRIMO Trial in R/R Peripheral T-Cell Lymphoma

Jonathan E. Brammer, MD,discusses data from the following poster: “Duvelisib in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma From the Phase 2 PRIMO Trial: Results of an Interim Analysis” Brammer J, et al. ASH 2021, Abstract 2456).

Introduction

• Relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) is a family of aggressive lymphomas, with a median overall survival (OS) of less than 6 months. Current FDA-approved therapies for R/R PTCL have modest overall response rates (ORRs) of < 30%.
• In the phase 2, open-label, multicenter, parallel cohort PRIMO trial of duvelisib (a dual PI3K-δ,γ inhibitor) in R/R PTCL, the initial results of the dose-optimization phase (N=33) demonstrated a 54% ORR in the 75 mg twice a day (N=13) and 35% in the 25 mg twice a day (N=20) cohorts, respectively.
• The objective of this presentation was to provide the interim results as of May 21, 2021, including the first 6 months of data for the 78 patients included in the analysis obtained from the PRIMO trial expansion phase.

Methods

• PRIMO is a phase 2, open-label, multicenter, parallel cohort study of duvelisib in patients with R/R PTCL consisting of a dose optimization phase and an expansion phase (NCT03372057).
• The expansion phase of PRIMO has a targeted enrollment of 125 patients. The expansion phase eligibility criteria included histologically confirmed R/R PTCL after >1 cycle of a prior standard regimen, a CD4 lymphocyte count of ≥ 50 per mm3 and required pneumocystis jiroveci prophylaxis.
• Based on the dose optimization results, patients in the expansion phase receive duvelisib at 75 mg twice a day for 2 cycles to maximize rapid tumor control, followed by 25 mg twice a day to maintain long-term disease control and mitigate late toxicities, until progressive disease or unacceptable toxicity.
• The primary end point is ORR by independent review committee assessment. Secondary end points include ORR by investigator assessment, duration of response (DOR), progression-free survival, OS, disease control rate, and safety. All analyses consisted of patients who received at least 1 dose of duvelisib.

Results

• The interim results of the first 78 patients in the PRIMO expansion phase show an ORR of 50% and a CR rate of 32%.
• Time to response was 53 days (range, 15 to 114 days), and median duration of response was 233 days (range, 1 to 420 days).
• The most frequent grade ≥3 adverse events (AEs) were neutropenia, increased ALT/AST, rash, lymphocyte count decreased, and sepsis. Alanine aminotransferase and aspartate aminotransferase elevations were the most common AEs leading to treatment discontinuation.

Conclusion

• Response rates with duvelisib suggest that this therapy is superior to available standard-of-care therapeutic options. These data build upon prior reports demonstrating duvelisib as an active oral treatment for patients with R/R PTCL.
• Duvelisib was well tolerated in the given patient population and remained consistent with its known safety profile.