10 Dec PRIMO Trial: Dose Optimization of Duvelisib in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma
MedicalResearch.com Interview with:
Steven M. Horwitz, MD
Memorial Sloan Kettering Cancer Center
New York, NY
MedicalResearch.com: What is the background for this study?
Response: Relapsed or refractory Peripheral T-Cell Lymphoma (R/R PTCL) remains a disease of significant unmet medical need.
Duvelisib is an oral dual inhibitor of PI3K-δ and PI3K-γ approved for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies, relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies, and is being developed for the treatment of additional hematologic malignancies including R/R PTCL.
In early studies, we saw a suggestion of quite good activity of duvelisib as a single agent in a range of subtypes of T-cell lymphoma.
The PRIMO study is an ongoing, multi-center, open-label, registration-directed Phase 2 study evaluating duvelisib in patients with R/R PTCL that is expected to enroll approximately 120 patients. The study includes both a dose optimization phase and an expansion phase.
The Primo study will be sufficiently powered to give a much more precise estimate of the activity in peripheral t cell lymphomas. However, prior to initiating the main cohort we needed to first try to identify an optimal dose. That “dose optimization cohort” is the subject of our presentation here.
MedicalResearch.com: What are the main findings?
Response: In the dose optimization portion of the study, patients were randomized to receive duvelisib 25mg twice daily (cohort 1) or duvelisib 75mg twice daily continuously (cohort 2) until disease progression or unacceptable toxicity. The primary endpoint of the study was investigator-assessed overall response rate (ORR), and secondary endpoints included duration of response (DOR) and safety.
The investigator-assessed ORR in the ITT population was 35% in cohort 1 (n=20) and 54% in cohort 2 (n=13), with a complete response rate (CR) of 25% and 31% in cohort 1 and cohort 2, respectively. The ORR assessed by a blinded independent review, also in the ITT population, was 40% and 62% for cohort 1 and cohort 2, respectively. Nearly all of the responses were identified on first assessment. The most common (≥4 patients) Grade ≥3 adverse events (AEs) in all patients receiving duvelisib were neutropenia, thrombocytopenia, diarrhea, rash/maculopapular, lymphocytopenia, pneumonia and sepsis. Serious AEs occurring in >2 patients were colitis, diarrhea, abdominal pain, pyrexia, sepsis, pneumonia, hyponatremia, rash/maculopapular, dyspnea, and respiratory failure. Overall, 12% of patients receiving duvelisib discontinued due to an AE.
MedicalResearch.com: What should readers take away from your report?
Response: It appears that while there were responses, including complete responses at both the 25mg twice daily and duvelisib 75mg twice daily cohorts, more patients had early progression in the 25mg twice daily cohort. The analysis of drug levels (pk) in cycle 1 suggest that higher levels of drug in the blood seen in the 75mg twice daily may correlate with better early disease control. Due to this finding, patients in the rest of the study will start with 75 mg twice daily dosing but then have their dose reduced to hopefully minimize any long-term side effects.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: This was the first phase of the larger primo study. The main expansion phase of this registration-directed study is currently underway in the United States and is opening in Germany, UK, Italy, and Japan.
Steven Horwitz: Trillium: Research Funding; Seattle Genetics: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Forty-Seven: Research Funding; Portola: Consultancy; Innate Pharma: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Kyowa Hakko Kirin: Consultancy; Celgene: Consultancy, Research Funding; Kura: Consultancy; Astex: Consultancy; Aileron: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Miragen: Consultancy; Affimed: Consultancy; ADCT Therapeutics: Research Funding; Mundipharma: Consultancy.
Off Label Disclosure: Duvelisib (DUV), a dual PI3K-delta,gamma inhibitor, is US FDA approved at 25 mg twice daily (BID) for the treatment of R/R chronic lymphocytic leukemia or small lymphocytic lymphoma after at least 2 lines of prior therapy and R/R follicular lymphoma after at least two prior systemic therapies.
1567 Dose Optimization of Duvelisib in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma from the Phase 2 Primo Trial: Selection of Regimen for the Dose-Expansion Phase
Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Poster I
Hematology Disease Topics & Pathways:
Diseases, Adult, Non-Biological, Therapies, Biological Processes, immune cells, Cell Lineage, Study Population, Clinically relevant, Lymphoid Malignancies, immune mechanism
ASH December 7, 2019
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