Janssen-Cilag International Announces Three-Year Follow-Up Data from the Phase III RAY Study in Patients with Relapsed or Refractory Mantle Cell Lymphoma
Jun 19 17
Janssen-Cilag International NV has announced three-year follow-up data from the phase III RAY study in patients with relapsed or refractory mantle cell lymphoma (MCL). These results demonstrated that the subset of patients treated with IMBRUVICA (ibrutinib) at first relapse after one prior line of therapy achieved a median progression-free survival (PFS) of more than two years (25.4 months). This was four-fold longer than treatment with temsirolimus (6.2 months [HR, 0.40; 95% CI, 0.25-0.64]).1 Data showed median overall survival (OS) with ibrutinib after one prior line of therapy of 3.5 years (42.1 months vs 27.0 months with temsirolimus [HR, 0.74; 95% CI, 0.43-1.30]). Results from the Phase III, international, randomized, open-label RAY study were presented on June 17, 2017 during an oral session at the 14th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland. Ibrutinib, a first-in-class Bruton's tyrosine kinase (BTK) inhibitor, is jointly developed and commercialized by Janssen Biotech Inc. and Pharmacyclics LLC, an AbbVie company. In the overall study patient population, which included patients who had received more than one prior line of therapy (median two prior therapies), median PFS was also significantly increased in patients treated with ibrutinib vs temsirolimus (15.6 months vs 6.2 months [HR, 0.45; 95% CI, 0.35-0.60; p< 0.0001]).1 In addition, ibrutinib tended to increase OS, with a median OS with ibrutinib of 30.3 vs 23.5 months with temsirolimus (HR, 0.74; 95% CI, 0.54-1.02; p=0.0621). Complete response (CR) was achieved in nearly a quarter (23.0%) of all patients who received ibrutinib.1 The CR rate in patients who had received one line of therapy prior to ibrutinib (33.3%) was more than double that achieved in patients who had received more than one line of therapy prior to ibrutinib (15.9%).1 The duration of response in all patients who achieved a CR with ibrutinib was almost three years (35.6 months). The safety profile was consistent with primary analysis and known safety data on ibrutinib. No new safety signals for ibrutinib were observed in the trial. Overall frequencies of adverse events (AEs) were similar or lower in the ibrutinib arm, even with longer treatment exposure. Nearly twice as many patients discontinued temsirolimus due to AEs vs ibrutinib (31.7% vs 17.3%).1 In addition, exposure adjusted rates of atrial fibrillation were similar between the two groups (0.392 vs 0.331 with ibrutinib and temsirolimus, respectively) and exposure adjusted bleeding rates were lower with ibrutinib vs temsirolimus (2.880 vs 6.683).1 In the ibrutinib arm, Grade >/3 AEs included thrombocytopenia, anaemia and neutropenia in 9.4%, 8.6% and 12.9% of patients respectively. MCL is an incurable, aggressive B-cell malignancy with a median OS of three to four years. Most patients relapse after first-line therapy and have a poor prognosis. Despite recent advances and with the exception of a small patient population eligible for allogeneic stem cell transplant, there is no globally recognized standard of care in relapsed MCL. The Phase III, randomized, open-label RAY study compared ibrutinib with temsirolimus in patients with relapsed or refractory mantle cell lymphoma and >/1 prior rituximab-containing therapy.7 Two hundred and eighty patients were randomized 1:1 to oral ibrutinib (560 mg once-daily; n = 139) or intravenous temsirolimus (175 mg: days 1, 8, 15 of cycle 1; 75 mg: days 1, 8, 15 of subsequent cycles; n = 141) until disease progression/unacceptable toxicity. Long-term efficacy was investigator-assessed. Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor, which works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B-cells. By blocking this BTK protein, ibrutinib helps kill and reduce the number of cancer cells, thereby delaying progression of the cancer. Ibrutinib is currently approved in Europe for the following uses: As a single agent for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL), adult patients with relapsed or refractory mantle cell lymphoma (MCL), or adult patients with Waldenstrom's Macroglobulinaemia (WM) who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemo-immunotherapy. 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.
Janssen-Cilag International NV Announces Long-Term Results from SIRROUND-T
Jun 14 17
Janssen-Cilag International NV announced long-term results from SIRROUND-T, a pivotal Phase 3 study that showed sirukumab improved the signs and symptoms of moderately to severely active rheumatoid arthritis (RA) through 52 weeks of treatment in adult patients with an inadequate response and/or intolerance to anti-tumour necrosis factor (TNF)-alpha treatments. This is a typically difficult-to-treat population, representative of clinical practice where up to 40% of RA patients do not respond to biologics. This study and other data from the SIRROUND clinical programme will be presented in 11 abstracts accepted for presentation at the Annual European Congress of Rheumatology (EULAR) 2017 in Madrid, Spain. Data from the SIRROUND-T study showed that more than half of patients receiving either sirukumab 50 mg or 100 mg achieved at least a 20% improvement in the signs and symptoms of disease (ACR20) at week 52 (54.3% sirukumab 50 mg; 59.3% sirukumab 100 mg). Patients receiving sirukumab also demonstrated clinically meaningful improvements from baseline through week 52 in quality of life measures, as demonstrated by the health assessment questionnaire disability index (HAQ-DI) and the short form-36 (SF-36) health survey, for patient-reported outcomes in both physical and emotional well-being. The incidences of adverse events (AEs) and serious AEs were comparable between sirukumab 50 mg (79.6% and 14.2%, respectively) and sirukumab 100 mg (81.3% and 13.2%, respectively). Two additional poster presentations evaluated improvements in Health-Related Quality of Life (HRQoL) compared with an age/gender matched normal population in patients with RA and an inadequate response to conventional disease-modifying anti-rheumatic drugs (DMARDS) and anti-TNFs (SIRROUND-D and SIRROUND-T Phase 3 studies, respectively). The post-hoc analyses found that treatment with sirukumab resulted in greater and clinically meaningful improvements in HRQoL at week 24 compared with patients receiving placebo (P<0.001), with similar results observed across sirukumab doses (50 mg every 4 weeks and 100 mg every 2 weeks). An oral presentation of a post-hoc analysis (SIRROUND-D) highlighted the effect of sirukumab plus methotrexate on circulating biomarkers and demonstrated that in addition to inhibiting radiographic progression (bone destruction measured on x-ray images), treatment with sirukumab strongly inhibited biomarkers of bone and tissue destruction, and enhanced markers of bone formation.
Janssen-Cilag International Nv Announces Additional Follow-Up Data from the Phase 3 RESONATE Trial
Jun 5 17
Janssen-Cilag International NV announced longer follow-up of up to four years from the pivotal Phase 3 RESONATE™ trial (PCYC-1112) of Imbruvica® - (ibrutinib) vs. ofatumumab in patients with relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL). At a median follow-up of 44 months, the results demonstrated three year progression-free survival (PFS) rate of 59% vs. 3% with ibrutinib vs. ofatumumab respectively. A consistent PFS benefit with ibrutinib was observed across all baseline disease and patient characteristics, particularly among patients with genetic mutation deletion 11q (del11q), which is a prognostic feature usually conferring an increased risk for poor outcomes. With longer follow-up the overall response rate (ORR) has now reached 91%, with a complete response or complete response with incomplete bone marrow recovery (CR/CRi) rate of 9%. These results will be presented June 5, 2017 at the 53rd Annual American Society of Clinical Oncology (ASCO) Meeting in Chicago (poster session: 8:00 a.m. – 11:30 a.m. CDT; poster discussion: 1:15 p.m. – 2:30 p.m. CDT). Ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialised by Janssen Biotech Inc. and Pharmacyclics LLC, an AbbVie company. CLL is typically a slow-growing blood cancer of the white blood cells.2 The incidence of CLL in Europe among men and women is approximately 5.87 and 4.01 cases per 100,000 persons per year, respectively.3 CLL is predominantly a disease of the elderly, with a median age of 72 years at diagnosis.