Duvelisib Shows Significant Activity in R/R Peripheral T-Cell Lymphoma

Duvelisib (Copiktra) exhibited tolerability and significant activity among patients with relapsed/refractory peripheral T-cell lymphoma (PTCL), according to final results from the phase 2 PRIMO-EP trial (NCT03372057) published in the Journal of Clinical Oncology.¹Additionally, prior results were presented at the 2024 American Society of Hematology (ASH) Annual Meeting and Exposition.²

What were the key efficacy data of the PRIMO-EP trial?

Specifically, among 123 patients treated with the investigational monotherapy, the objective response rate (ORR) was 48.0% and the median time to response was 1.8 months. Moreover, the complete response (CR) rate was 33.3%. Of 41 patients who experienced a CR, 27 (66%) experienced a response within 8 weeks of treatment. Furthermore, the greatest response benefit was observed in the angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified subgroups, with respective ORRs of 62.2% and 51.4%, CR rates of 51.4% and 30.2%, and durations of response (DORs) of 11.7 months vs 7.4 months.

The median overall survival (OS) for all comers was 12.4 months (95% CI, 8.4-22.7), with a median value of 18.1 months (95% CI, 9.6-not calculable [NC]) and 11.0 months (95% CI, 5.1-30.4) in the AITL and PTCL not otherwise specified subgroups. Among all comers, the median DOR was 7.9 months (95% CI, 6.4-21.0) and the median progression-free survival (PFS) by independent review committee (IRC) was 3.4 months (95% CI, 1.8-3.9).

“Considering the poor prognosis and limited treatment options for patients with [relapsed/refractory] PTCL, the PRIMO-EP results demonstrated that duvelisib 75 mg [twice daily] for 2 cycles followed by 25 mg [twice daily] is an effective and tolerable therapy for [this population],” Neha Mehta-Shah, MD, MSCI, associate professor in the Division of Oncology of the John T. Milliken Department of Medicine of Washington University, wrote in the publication with study coinvestigators.¹ “In comparison to currently available single agents for PTCL, duvelisib has a favorable ORR of 48% [and CR rate of 33%] with short time to response. Unexpected toxicities were not seen on this study; [adverse effects (AEs)] were found to be reversible and manageable without treatment discontinuation in most cases.”

Phase 2 PRIMO-EP Trial Design

Patients who were 18 years and older with histologically confirmed PTCL per WHO 2016 classification and who received at least 2 cycles of standard regimen therapy for newly diagnosed advanced PTCL were assigned to receive escalating doses of duvelisib. Cohort 1 received the agent orally twice daily at 25 mg, with the potential to escalate to 50 mg or 75 mg twice daily based on response with and tolerance to therapy. Cohort 2 began with 75 mg of twice daily duvelisib. Both cohorts were treated in continuous, 28-day cycles.

The primary end point of the trial was investigator-assessed ORR in the dose optimalization phase and ORR by IRC per Lugano 2014 criteria in the PRIMO-EP portion of the trial. Secondary end points included DOR, PFS, disease control rate, OS, and treatment-emergent AEs (TEAEs).

Safety Findings

TEAEs of any cause occurred among 97.6% of patients, 74.0% of whom experienced grade 3 events. A total of 44.7% and 9.8% of patients experienced dose interruptions or reductions of therapy, with a further 33.3% experiencing discontinuation attributable to therapy. The most common TEAEs resulting in dose discontinuation included aspartate aminotransferase increases (7.3%), alanine aminotransferase increases (6.5%), and diarrhea (5.7%).

Fatal TEAEs not related to disease progression occurred in 10 patients, 4 of which were related to treatment. Of the 4 treatment-related fatal TEAEs, 3 were related to immunosuppression and 1 was immune-mediated.

References

1. Mehta-Shah N, Zinzani PL, Jacobsen ED, et al. Duvelisib induces deep responses in PTCL: final results of the phase 2 PRIMO trial of duvelisib in relapsed/refractory peripheral T-cell lymphoma. J Clin Oncol. Published April 22, 2026. doi:10.1200/JCO-25-03120
2. Mehta-Shah N, Zinzani PL, Jacobsen ED, et al. Duvelisib in patients with relapsed/refractory peripheral T-cell lymphoma: final results from the phase 2 PRIMO trial. Blood. 2024;144(suppl 1):3061. doi: 10.1182/blood-2024-203577