On December 4, 2020 Johnson & Johnson reported that New data from the Phase 2 CAPTIVATE study (PCYC-1142) were presented today during an oral session at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Abstract #123) (Press release, Johnson & Johnson, DEC 4, 2020, View Source;Based-Regimen-as-Fixed-Duration-First-Line-Treatment-for-Patients-with-Chronic-Lymphocytic-Leukaemia [SID1234572247]).1 The study evaluated the efficacy and safety of IMBRUVICA (ibrutinib) plus venetoclax in the treatment of adult patients with chronic lymphocytic leukaemia (CLL) and showed that, after achieving undetectable minimal residual disease (uMRD) in both the blood and bone marrow with the ibrutinib combination regimen, the one-year disease-free survival (DFS) of patients randomised to discontinue active treatment was comparable to that of patients randomised to continue ibrutinib monotherapy (95.3 percent vs. 100 percent, respectively [p=0.1475]).1
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"These data demonstrate the potential of this oral, once-daily, chemotherapy-free combination regimen in first-line treatment of CLL," said William Wierda,* M.D., Professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center and principal study investigator. "Once-daily treatment with ibrutinib remains the established standard of care in CLL; the latest results from the CAPTIVATE study underscore that the mechanistic synergy of ibrutinib and venetoclax delivers deep MRD remissions in the blood and bone marrow and enables treatment-free periods for patients."
The CAPTIVATE trial is evaluating adult patients younger than 70 years, including patients with high-risk disease, in two cohorts: an MRD Guided Cohort where treatment duration is guided by the patient’s MRD status after 12 cycles of combination ibrutinib plus venetoclax therapy; and a Fixed Duration Cohort where all patients stop therapy after 12 cycles of the combination, regardless of MRD status. Patients in the MRD Guided Cohort (n=164; median age, 58 years) who achieved uMRD, defined as having uMRD (<10–4 by 8-color flow cytometry) serially over at least three cycles and undetectable MRD in both peripheral blood (PB) and bone marrow (BM) with combination therapy, were randomised in a double-blinded fashion to continue treatment with ibrutinib monotherapy or placebo until disease progression.1
Patients in the MRD Guided Cohort who did not achieve uMRD following 12 cycles of combination ibrutinib plus venetoclax therapy were randomised to continue ibrutinib monotherapy or the combination.1 With a median total treatment duration of 28.6 months (range, 0.5-39.8) with ibrutinib and 12.0 months (range, 0.8-34.1) with venetoclax, increases in uMRD rates were greater with continued combination therapy versus continued ibrutinib monotherapy.1,2 Across all four randomised arms, 30-month progression-free survival rates were 95 percent or greater.1,2
The safety profile of the ibrutinib plus venetoclax regimen was consistent with known safety profiles of the individual therapies.1 Across all treated patients, the most common grade 3/4 adverse events (AEs) were neutropenia (36 percent), hypertension (10 percent), thrombocytopenia (5 percent), and diarrhoea (5 percent).1
"Ibrutinib is the only Bruton’s tyrosine kinase inhibitor that has shown significant overall survival and progression-free survival benefits in randomised Phase 3 studies in first-line CLL, and it continues to demonstrate efficacy and safety across regimens and patient subgroups, including those with historically poor outcomes," said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. "Results from the randomised phase of the MRD Guided Cohort of the CAPTIVATE study show that treatment-free remissions are possible with ibrutinib-based fixed duration therapy, providing yet another treatment option for patients starting first-line CLL treatment."
"Ibrutinib has impacted more than 200,000 patients worldwide and the CAPTIVATE study provides more evidence in support of the lasting effect that can be achieved in people living with CLL over time," adds Dr Catherine Taylor, Vice President, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd., Middle East. "The manageable safety profile of the ibrutinib combination with a low rate of discontinuation underscores this regimen as a potential viable option and we are excited to explore how it can benefit patients in a front-line setting."
The registrational Phase 3 GLOW study, assessing ibrutinib plus venetoclax in comparison to chlorambucil plus obinutuzumab for first-line treatment of elderly or younger unfit patients with CLL (NCT03462719) is ongoing as part of the comprehensive development programme exploring the potential of ibrutinib-based fixed duration therapy.3
*William Wierda is the lead investigator of the CAPTIVATE study. He was not compensated for any media work.
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About Ibrutinib
Ibrutinib is a once-daily, first-in-class Bruton’s tyrosine kinase (BTK) inhibitor that is administered orally, and is jointly developed and commercialised by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.4 Ibrutinib blocks the BTK protein; the BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signalling is needed by specific cancer cells to multiply and spread.5 By blocking BTK, ibrutinib may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.6
Indications for which ibrutinib is approved in Europe include:3
Chronic lymphocytic leukaemia (CLL): As a single agent or in combination with rituximab or obinutuzumab for the treatment of adult patients with previously untreated CLL, and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy
Mantle cell lymphoma (MCL): As a single agent for the treatment of adult patients with relapsed or refractory MCL
Waldenström’s macroglobulinemia (WM): As a single agent for the treatment of adult patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemo-immunotherapy, and in combination with rituximab for the treatment of adult patients
Ibrutinib is approved in more than 100 countries for at least one indication, and to date, has been used to treat more than 200,000 patients worldwide.7
For a full list of side effects and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics for further information.
About Chronic Lymphocytic Leukaemia
Chronic lymphocytic leukaemia (CLL) is typically a slow-growing blood cancer of the white blood cells.8 The overall incidence of CLL in Europe is approximately 4.92 cases per 100,000 persons per year and is about 1.5 times more common in men than in women.9 CLL is predominantly a disease of the elderly, with a median age of 72 years at diagnosis.10
The disease eventually progresses in the majority of patients, and they are faced with fewer treatment options with each relapse. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.