Phase I Study of Duvelisib and Venetoclax in Relapsed or Refractory CLL / SLL

MedicalResearch.com Interview with:



Dr. Matthew S. Davids MD MSC

Associate Director of the Dana-Farber CLL Center

Attending physician

Lymphoma Program, Division of Hematologic Malignancies

Dana-Farber

Dr. Jennifer Crombie MD

Instructor in Medicine

Harvard Medical School





MedicalResearch.com: What is the background for this study?

Response: New data from our investigator-sponsored Phase 1 study exploring duvelisib in combination with venetoclax will be presented at ASH on December 7. In relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), duvelisib plus venetoclax demonstrated promising clinical activity, a manageable tolerability profile, and identified a recommended Phase 2 dosing (RP2D) regimen.

MedicalResearch.com: What are the main findings?

Response: In the study, 12 patients were enrolled and received oral duvelisib and oral venetoclax.

The primary endpoints of the study were dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and identification of the RP2D. Secondary endpoints included pharmacokinetics and preliminary efficacy.

Among the 12 evaluable patients, 11 achieved a response (ORR=92%), including four (33%) complete responses and seven (58%) partial responses. Four patients had undetectable minimum residual disease (uMRD) in the peripheral blood and bone marrow, including two patients with a complete response. The most common Grade 1 and 2 adverse reactions (AEs) were fatigue (92%), hyperglycemia (83%), anemia (67%), and thrombocytopenia (67%). The most common Grade ≥3 AEs were neutropenia (84%), hypocalcemia (50%), and hypophosphatemia (25%). No tumor lysis syndrome (TLS) occurred. No DLTs were observed, and the RP2D was identified as duvelisib 25mg twice daily and venetoclax 400mg once daily.

MedicalResearch.com: What should readers take away from your report?

Response: The study indicates early signals of robust activity combined with a manageable tolerability profile when exploring this oral combination of duvelisib and venetoclax. Importantly, the study also identified the recommended Phase 2 dosing regimen for this combination for patients.

It is also important to note that the patients in this study were heavily pre-treated, including 10 out of 12 (83%) who had previously received a BTK inhibitor.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Exploring the combination of duvelisib plus venetoclax in this patient population is a promising pathway for future study. A phase 2 portion of this study is now actively accruing and includes a separate cohort of patients with Richter’s syndrome, an aggressive disease with high unmet need.

Title: The Dual PI3K-δ/γ Inhibitor Duvelisib in Combination with the Bcl-2 Inhibitor Venetoclax Shows Promising Responses in Richter Syndrome-PDX Models

Lead author: Andrea Iannello, University of Turin

Poster #: 2862

Session: 625. Lymphoma: Pre-Clinical—Chemotherapy and Biologic Agents: Poster II

Sunday, December 8, 2019

MedicalResearch.com: Is there anything else you would like to add?

Response: The early efficacy of this oral combination is promising, as evidenced by those patients who achieved CRs and uMRD after a short amount of time on venetoclax. We look forward to the continuation of this trial for these patients with relapsed or refractory CLL or SLL who are in need of additional options.

We presented the data from the Phase 1 Study at ASH on Saturday, December 7 from 5:30-7:30pm. More details below:

Title: A Phase I Study of Duvelisib and Venetoclax in Patients with Relapsed or Refractory CLL / SLL

Lead authors: Matthew Davids and Jennifer Crombie, Dana-Farber Cancer Institute

Poster #: 1763

Session: 642. CLL: Therapy, excluding Transplantation: Poster I

Date and Time: Saturday, December 7, 2019; 5:30-7:30 PM ET

Location: Orange County Convention Center, Hall B

Disclosures:

Jennifer Crombie: Nothing to disclose

Matthew S. Davids: Research to Practice: Honoraria; AbbVie, Acerta Pharma, Adaptive, Biotechnologies, Astra-Zeneca, Genentech, Gilead Sciences, Janssen, Pharmacyclics, TG therapeutics: Membership on an entity’s Board of Directors or advisory committees; AbbVie, Astra-Zeneca, Genentech, Janssen, MEI, Pharmacyclics, Syros Pharmaceuticals, Verastem: Consultancy; Acerta Pharma, Ascentage Pharma, Genentech, MEI pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, Verastem: Research Funding.

Off Label Disclosure

Citation:

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

https://ash.confex.com/ash/2019/webprogram/Paper121401.html

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