On December 7, 2019 The Janssen Pharmaceutical Companies of Johnson & Johnson reported combination data from two studies and a long-term integrated analysis evaluating the use of Imbruvica (ibrutinib) for the treatment of previously untreated patients with CLL (Press release, Janssen Pharmaceuticals, DEC 7, 2019, View Source [SID1234552057]). Results from a 48-month follow-up analysis of the Phase 3 E1912 clinical study reported a statistically significant difference in PFS and OS for ibrutinib plus rituximab compared to a standard chemoimmunotherapy regimen of FCR.1 Further, the latest integrated analysis from the Phase 3 RESONATETM (PCYC-1112) and RESONATETM-2 (PCYC-1115/1116) studies investigating the use of single-agent ibrutinib in CLL, reported at up to six years of follow-up, PFS, OS and response rates improved when ibrutinib was used in earlier lines of therapy.2 During this extended follow-up, ibrutinib was tolerated across all lines of therapy with 19 percent of patients discontinuing due to adverse events.2

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The data presented at ASH (Free ASH Whitepaper) adds to the robust body of evidence supporting the safety and efficacy of ibrutinib in the first-line, as a monotherapy or in combination with other treatments"

Tweet this
In addition, results presented from the Phase 2 CAPTIVATE study suggested that patients who received ibrutinib plus venetoclax as a time-limited treatment achieved high rates of uMRD in peripheral blood (75 percent of patients) and bone marrow (72 percent of patients).3

These new findings from the E1912, RESONATE/RESONATETM-2 and CAPTIVATE studies were presented at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

"We’re pleased to see follow-up results from the Phase 3 E1912 trial, where the investigational use of ibrutinib plus rituximab is shown to extend OS for previously untreated patients with CLL. In addition, with the integrated analysis of the Phase 3 RESONATE and RESONATE-2 studies, ibrutinib demonstrated an OS benefit in untreated and relapsed patients, with improved outcomes in early lines of therapy," said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. "We are also excited to see the first MRD data from the fixed-duration regimen of ibrutinib plus venetoclax in the Phase 2 CAPTIVATE trial, reporting a high rate of undetectable MRD at 15 months both in the peripheral blood and bone marrow."

"The data presented at ASH (Free ASH Whitepaper) adds to the robust body of evidence supporting the safety and efficacy of ibrutinib in the first-line, as a monotherapy or in combination with other treatments," said Dr Patrick Laroche, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag. "As chemotherapy is not suitable for all patients there remains a need for non-chemotherapy treatment options and we are committed to exploring various ibrutinib-based combination regimens."

E1912 extended follow-up of investigational use of ibrutinib plus rituximab compared to FCR in patients with CLL ages 70 or younger (Abstract #33)1

Longer-term outcomes data from the Phase 3 E1912 clinical trial – designed and conducted by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health – were also presented. As previously reported in earlier data readouts, the study evaluated 354 previously untreated patients with CLL ages 70 years or younger who were randomly assigned to receive ibrutinib and rituximab or six courses of intravenous FCR every 28 days.1

At a median follow-up of 48 months, 73 percent of patients in the ibrutinib plus rituximab treatment arm remained on ibrutinib with median time on treatment of 43 months.1 PFS benefits were observed for the ibrutinib plus rituximab arm as compared to the FCR treatment arm (hazard ratio [HR]=0.39; 95 percent confidence interval [CI], 0.26-0.57; p<0.0001).1 OS benefit also continued to favour the ibrutinib plus rituximab arm (HR=0.34; 95 percent CI, 0.15-0.79; p=0.009).1

Grade 3 and above treatment-related adverse events (AEs) were observed in 70 percent of patients in the ibrutinib plus rituximab arm versus 80 percent in the FCR arm (odds ratio [OR]=0.56; 95 percent CI, 0.34-0.90; p=0.013).1

MRD cohort of the Phase 2 CAPTIVATE study on ibrutinib plus venetoclax combination in patients with previously untreated CLL (Abstract #35)3

The Phase 2 CAPTIVATE (PCYC-1142) clinical trial evaluated 164 patients younger than 70 years (median age of 58 years) with previously untreated CLL.3 Patients received ibrutinib monotherapy as lead-in treatment for three cycles, followed by 12 cycles of ibrutinib plus venetoclax combination therapy.3 MRD status was evaluated in peripheral blood (PB) after six, nine, and 12 cycles and in bone marrow (BM) after 12 cycles of ibrutinib plus venetoclax.3

"The new results from the CAPTIVATE study demonstrated the all-oral regimen of ibrutinib monotherapy followed by combined ibrutinib and venetoclax achieved promising rates of undetectable minimal residual disease, an important indicator of deep response, in previously untreated patients with CLL," said Constantine Tam, M.D., Haematologist and Disease Group Lead, Low Grade Lymphoma and CLL, Peter MacCallum Cancer Centre, Victoria, Australia, and principal study investigator. "We look forward to continuing to explore the efficacy and safety profile of this regimen and its potential to provide a limited-duration option in first-line treatment of CLL."

Results showed uMRD – defined as less than one CLL cell per 10,000 leukocytes (MRD<0.01 percent) by flow cytometry – was achieved at any time after baseline in PB for 75 percent of patients (122 of 163 patients) and in BM for 72 percent (111 of 155 patients).3 The high rates of uMRD in BM were consistent across high-risk subgroups, including in patients with del(17p); del(17p) or TP53 mutation; del(11q); complex karyotype; and unmutated IGHV status. In patients with uMRD in PB with matched BM samples, 93 percent of patients had uMRD in both PB and BM. With median follow-up of 14.7 months, three patients (2 percent) experienced disease progression.3,4

The most common AEs of any grade (in 20 percent of patients or greater) were diarrhoea (31 percent) and arthralgia (22 percent) during treatment with ibrutinib alone; and diarrhoea (60 percent), neutropenia (40 percent), nausea (34 percent), upper respiratory tract infection (24 percent), and fatigue (20 percent) during treatment with ibrutinib plus venetoclax. AEs leading to dose reductions occurred in 20 percent of patients overall. AEs leading to discontinuation were infrequent, occurring in 7 percent of patients overall (ibrutinib: 5 percent; venetoclax: 4 percent).3,4

Results from the MRD-guided, randomised treatment discontinuation cohort and fixed-duration cohort of the CAPTIVATE clinical trial are being further evaluated and will be presented at a future medical meeting.

Ibrutinib, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialised by Janssen Biotech, Inc., and Pharmacyclics LLC, an AbbVie company.

#ENDS#

About ibrutinib

Ibrutinib is a once-daily, first-in-class Bruton’s tyrosine kinase (BTK) inhibitor that is administered orally.5 Ibrutinib blocks the BTK protein; the BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signaling is needed by specific cancer cells to multiply and spread.6 By blocking BTK, ibrutinib may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.7

Ibrutinib is currently approved in Europe for:5

Chronic lymphocytic leukaemia (CLL): As a single agent or in combination with 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 95 countries for at least one indication, and to date, has been used to treat more than 170,000 patients worldwide across its approved indications.8

The most common adverse reactions seen with ibrutinib include diarrhoea, neutropenia, haemorrhage (e.g., bruising), musculoskeletal pain, nausea, rash, and pyrexia.5

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.9 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.10 CLL is predominantly a disease of the elderly, with a median age of 72 years at diagnosis.11

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.