IBRUTINIB LEAD-IN FOLLOWED BY VENETOCLAX IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: PHASE 2 CAPTIVATE EARLY SAFETY AND EFFICACY RESULTS
Author(s): ,
Paolo Ghia
Affiliations:
Department of OncoHematology,Università Vita-Salute San Raffaele,Milano,Italy
,
Constantine Tam
Affiliations:
Peter MacCallum Cancer Centre and St. Vincent's Hospital,Melbourne,Australia
,
Tanya Siddiqi
Affiliations:
City of Hope National Medical Center,Duarte, CA,United States
,
Ian Flinn
Affiliations:
Sarah Cannon Research Institute/Tennessee Oncology,Nashville, TN,United States
,
Xavier Badoux
Affiliations:
St George Hospital,Sydney,Australia
,
Thomas Kipps
Affiliations:
University of California San Diego, Moores Cancer Center,San Diego, CA,United States
,
John Allan
Affiliations:
Weill Cornell Medicine,New York, NY,United States
,
Alessandra Tedeschi
Affiliations:
ASST Grande Ospedale Metropolitano Niguarda,Milano,Italy
,
John Pagel
Affiliations:
Swedish Cancer Institute,Seattle, WA,United States
,
Bryone Kuss
Affiliations:
Flinders Medical Centre,Adelaide,Australia
,
Eva Gonzalez-Barca
Affiliations:
Institut Català d’Oncologia L’Hospitalet, IDIBELL,Barcelona,Spain
,
Karl Eckert
Affiliations:
Pharmacyclics LLC, an AbbVie Company,Sunnyvale, CA,United States
,
Cathy Zhou
Affiliations:
Pharmacyclics LLC, an AbbVie Company,Sunnyvale, CA,United States
,
Joi Ninomoto
Affiliations:
Pharmacyclics LLC, an AbbVie Company,Sunnyvale, CA,United States
,
James Dean
Affiliations:
Pharmacyclics LLC, an AbbVie Company,Sunnyvale, CA,United States
,
Danelle James
Affiliations:
Pharmacyclics LLC, an AbbVie Company,Sunnyvale, CA,United States
William Wierda
Affiliations:
University of Texas MD Anderson Cancer Center,Houston, CA,United States
EHA Learning Center. GHIA P. Jun 16, 2018; 214522
Dr. Paolo GHIA
Dr. Paolo GHIA

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Abstract
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Abstract: S806

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 12:00 - 12:15

Location: Victoria Hall

Background
Ibrutinib (ibr), a first-in-class, once-daily BTK inhibitor, is approved in the US for CLL/SLL and in the EU for CLL treatment, including patients with del(17p). Single-agent ibr results in improved survival; however, rates of complete remission (CR) are low, and continuous therapy is required. Ibr and venetoclax (ven), a BCL-2 inhibitor approved by FDA, have complementary therapeutic activity, and synergistic anti-tumor activity has been shown in preclinical and clinical studies with these agents. Ven improves CR rates and can lead to minimal residual disease-negative (MRD(-)) responses in CLL, but increases tumor lysis syndrome (TLS) risk. Tumor debulking by single-agent ibr lead-in followed by combination ibr + ven (I+V) may improve clinical outcomes and lower TLS risk.

Aims
PCYC-1142 (CAPTIVATE) is a phase 2, multicenter study of I+V in first-line CLL (NCT02910583). The study is conducted in 2 phases. The first phase evaluates the MRD(-) clinical response rate of I+V, followed by MRD status-guided randomized treatment discontinuation. The overall objective is to evaluate whether achievement of MRD(-) remission after I+V allows for treatment holidays.

Methods
PCYC-1142 (CAPTIVATE) is a phase 2, multicenter study of I+V in first-line CLL (NCT02910583). The study is conducted in 2 phases. The first phase evaluates the MRD(-) clinical response rate of I+V, followed by MRD status-guided randomized treatment discontinuation. The overall objective is to evaluate whether achievement of MRD(-) remission after I+V allows for treatment holidays.

Results
At time of analysis, a total of 163 patients (median age, 58 years) were enrolled. The first 14 patients had completed the safety run-in of ibr lead-in and ≥6 cycles of I+V; 97 patients (including the safety run-in patients) had completed ibr lead-in and had initiated ven treatment (I+V Exposed). No dose-limiting toxicities occurred during safety run-in. At baseline, 14% of patients had del(17p), 15% had del(11q), and 33% had bulky disease with longest lymph node diameter (LDi) ≥5 cm. Of the 14 safety run-in patients, ORR was 100% (14/14; CR confirmed in 1/5 patients with early BM results at time of analysis and 13/14 confirmed PR); 9/11 assessed patients had MRD(-) status in PB. Common AEs (occurring in ≥20% of I+V Exposed patients) were diarrhea (39%), fatigue (23%), nausea (23%), and arthralgia (21%); grade ≥3 AEs in ≥3% were neutropenia (10%), hypertension (3%), and thrombocytopenia (3%). No patients met the clinical criteria for TLS; laboratory TLS was seen in 1/163. Of 30 I+V Exposed patients with baseline LDi ≥5 cm, 19 (63%) were reduced to LDi <5 cm after ibr lead-in. TLS risk was reduced to medium/low in 17/22 of high risk patients (77%). Overall, the proportion of patients with high-risk TLS decreased from a baseline of 23% to 3% after ibr lead-in.

Conclusion
These early study results support the safety, activity, and TLS risk reduction potential of ibr lead-in. The early data show promising activity of an I+V oral regimen with MRD(-) responses in 82% in first-line CLL. Safety profiles were consistent with AE profiles of single-agent ibr or ven. The protocol-specified efficacy analysis in the first 30 patients (including ORR) will be presented.

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Chronic Lymphocytic Leukemia, Clinical Trial, Minimal residual disease (MRD), Tumor lysis

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