Duvelisib Induces Encouraging ORR in Relapsed/Refractory Peripheral T-Cell Lymphoma

Duvelisib (Copiktra) monotherapy demonstrated encouraging efficacy for patients with relapsed/refractory peripheral T-cell lymphoma (PTCL), according to updated dose-expansion results of the phase 2 PRIMO trial (NCT03372057) that were presented at the 2021 Pan Pacific Lymphoma Conference.¹

At a median follow-up of 4 months, data showed that an independent review committee (IRC) recorded 20 (52.6%) responses, including 13 (34.2%) complete responses (CRs) in the 38-patient cohort. The median time to response was 55 days (29-114) and the median duration of response (DOR) was 233 days (range, 1+ to 334+).

Jasmin M. Zain, MD, director of the T-Cell Lymphoma Program and an associate clinical professor at City of Hope, presented the data from PRIMO, adding that duvelisib could be used as a bridge to transplant in this patient population.

“Monotherapy with duvelisib is a promising therapy for patients with relapsed/refractory PTCL, with ORR noted to be 50% with a complete response rate of 34% in the dose-expansion phase,” said Zain in presenting the findings.

She added that there is a clear medical need for new treatment options for the relapsed/refractory PTCL population.

“Patients with relapsed/refractory PTCL have a terrible prognosis with a median overall survival of less than 6 months,” she said. “Most approved therapies are associated with an overall response rate [ORR] of less than 30% and a median progression-free survival [PFS] of less than 4 months.

Duvelisib is an oral, dual inhibitor of phosphatidylinositol 3-kinase δ and γ (PI3K-δ,γ) that is currently approved relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma after at least 2 prior therapies, as well as relapsed/refractory follicular lymphoma after at least 2 prior systemic therapies.

In PRIMO, investigators are evaluating the efficacy of single-agent duvelisib at 75 mg twice daily in approximately 120 patients with relapsed/refractory PTCL in the trial’s dose-expansion phase. Patients must have the following: PTCL with PTCL-not otherwise specified (55.3%), AITCL (26.3%), ALCL (18.4%), or NKTL (0%); measurable disease per International Working Group for PTCL; no transformation to aggressive lymphoma; no prior history of allogeneic stem cell transplant or treatment with PI3K inhibitor; and an ECOG performance status of 0 to 2.

In the PRIMO dose-optimization cohort, 33 patients were treated with 25 mg (n = 20) or 75 mg (n = 13) twice daily. The investigator-assessed objective response rate (ORR) at the 75-mg dose was 54%, the CR rate was 31%, and the median DOR was 12.2 months.² The ICR-based ORR was 62% and the CR rate was not available. Based on these initial results, the researchers next treated patients in the dose-expansion phase with 75 mg of twice-daily duvelisib for 2 cycles to achieve tumor control, then with 25 mg of twice-daily duvelisib to maintain long-term disease control.

The primary end point is IRC-assessed ORR; secondary end points are safety, DOR, progression-free survival, disease control rate, and overall survival. Pharmacokinetic and pharmacodynamic markers are exploratory end points.

This dose-expansion phase included 38 patients. Women made up half the cohort and 73.7% of patients were White. The median time from initial diagnosis was 20 months (range, 6-196), and the median time from most recent relapsed/refractory diagnosis was 1.3 months (range, 0-143).

Investigators said the AE profile was consistent with previous PRIMO results. Overall, 32 patients (84%) discontinued treatment, half of which were due to disease progression (50%). Seven (18%) discontinued because of adverse events (AEs). Six (16%) patients remain on treatment.

Increased alanine aminotransferase (26%) and increased aspartate aminotransferase (24%) were the most common grade 3 or higher AEs. The only grade 3 or higher AE to appear in more than 5% of patients were decreased lymphocyte count (11%), rash (11%), and decreased neutrophil count (8%).

In June 2021, the European Medicines Agency granted marketing authorization for duvelisib monotherapy in patients with relapsed/refractory CLL who have previously received at least 2 therapies or those with follicular lymphoma whose disease is refractory to at least 2 previous systemic treatments.³

The decision was based on findings from the phase 3 DUO trial (NCT02004522), in which duvelisib reduced the risk of disease progression or death by 48% vs ofatumumab (Arzerra) in patients with relapsed/refractory CLL or SLL per IRC assessment.⁴ The median PFS in the investigative arm was 13.3 months (95% CI, 12.1-16.8) per IRC assessment vs 9.9 months (95% CI, 9.2-11.3) in the control arm (HR, 0.52; P <.0001).

References

1. Zain J, Zinzani PL, Brammer JE, et al. Duvelisib in patients with relapsed/refractory peripheral T-cell lymphoma from the phase 2 PRIMO trial: updated expansion phase results. Presented at: 2021 Pan Pacific Lymphoma Conference; August 9-13, 2021; Big Island, HI.
2. Pro B, Brammer JE, Casulo C, et al. Duvelisib in patients with relapsed/refractory peripheral T-cell lymphoma from the phase 2 PRIMO trial: Dose optimization efficacy update and expansion phase initial results. Blood. 2020;136(suppl 1):38-39. doi:10.1182/blood-2020-140412
3. COPIKTRA (duvelisib) receives European Union marketing authorization for the treatment of relapsed or refractory CLL and refractory FL. News release. Secura Bio, Inc. June 9, 2021. Accessed August 12, 2021. https://prn.to/3zfFVLV
4. Finn IW, Hillmen P, Montillo M, et al. The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. Blood. 2018;132(23):2446-2455. doi:10.1182/blood-2018-05-850461