LGBT Cancer Project

Lymphocytic Leukemia, Chronic

January 18, 2016

Genentech reported results of a phase II study of venetoclax for chronic lymphocytic leukemia (CLL). The study met its primary endpoint, with an overall response rate (ORR) of 79.4% with venetoclax, as assessed by an independent review committee (IRC). In addition, 7.5% of people achieved a complete response with or without complete recovery (complete response without normal blood counts) in the bone marrow. Forty-five people had an assessment for minimal residual disease (MRD) in the blood. Notably 18 people (17% of the total, 21% of responders) achieved MRD-negativity, meaning no cancer could be detected using a specific test. Ten of these 18 people also had bone marrow assessments and six were MRD-negative. At one year, 84.7% of all responses and 94.4% of MRD-negative responses were maintained. The one-year progression-free survival (PFS) and overall survival (OS) rates were 72% and 86.7%, respectively. No unexpected safety signals were reported. AbbVie has submitted an NDA for venetoclax to the FDA. Venetoclax received Breakthrough Therapy designation from the FDA earlier this year for the treatment of people with relapsed or refractory CLL harboring the 17p deletion. AbbVie also has submitted a marketing authorization application (MAA) to the EMA. Submissions to other regulatory authorities around the world are planned in 2016.

December 14, 2015

Janssen-Cilag International issued results of a randomized, multicenter, open-label, phase III trial of ibrutinib (IMBRUVICA) for treatment-naïve chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in patients aged 65 or older. Patients were randomized to receive either ibrutinib 420mg orally, once daily until progression or toxicity or chlorambucil 0.5 to 0.8mg/kg on days one and 15 of each 28-day cycle for up to 12 cycles. The primary endpoint of the study was PFS as assessed by an IRC according to the International Workshop on Chronic Lymphocytic Leukaemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis. The Independent Review Committee (IRC) found ibrutinib significantly prolonged PFS compared with chlorambucil. The hazard ratio (HR) was 0.16 (95% CI, 0.09-0.28; P<0.001), which represents a reduction in the risk of progression or death by 84% v. chlorambucil (median not reached v. 18.9 months); the PFS rate at 18 months was 90% for ibrutinib v. 52% for chlorambucil. Ibrutinib also significantly prolonged OS (HR=0.16: 95% CI, 0.05, 0.56; P=0.001) with a 24-month survival rate of 98%, compared to 85% for patients in the chlorambucil arm. Additionally, ibrutinib was associated with a significantly higher ORR (86% v. 35%; P<0.001) as assessed by the IRC and significantly increased the rate of sustained improvements in both haemoglobin and platelets. The RESONATE-2 results are the basis for a Type II variation application to the EMA seeking to broaden the existing marketing authorization for IMBRUVICA to include previously untreated patients with CLL. Janssen affiliates market IMBRUVICA in EMEA (Europe, Middle East and Africa) as well as the rest of the world, except for the U.S., where Janssen Biotech, Inc. and Pharmacyclics co-market it.

June 16, 2014

AbbVie issued results of phase Ib trials of ABT-199/GDC-0199 in combination with rituximab for relapsed/refractory chronic lymphocytic leukemia (CLL) and various subtypes of non-Hodgkin’s lymphoma (NHL). The phase I, open-label, multicenter, international trial of ABT-199/GDC-0199 in patients with relapsed/refractory CLL and NHL enrolled 78 patients in the CLL arm and 62 patients in the NHL arm of the trial. In the CLL arm, due to concerns of TLS, the initial dose was reduced from 50mg to 20mg and daily dosing was modified to a weekly rampup period to the final dose of 400mg. A ramp-up period with weekly dose increases occurred from 20mg, 50mg, 100mg, 200mg to the final recommended phase II dose (RPTD) of 400mg. The overall response rate (ORR) was 77%, with 23% achieving complete response (CR). Of the 18 CR/CRi patients (complete response with incomplete blood count recovery), 11 were evaluated for minimal residual disease (MRD) and six were found to be MRD negative. The ORR for patients with 17p deletion and F-refractory CLL was 79% and 76%, respectively. ABT- 199/GDC-0199 as a monotherapy in patients with relapsed/refractory CLL harboring the 17p deletion is under investigation in an ongoing phase II clinical trial.

November 12, 2012

MorphoSys and Xencor released results from a phase I/IIa trial of MOR208 (MOR00208/XmAb5574) for the treatment of tumor activity. This dose-ranging study enrolled patients with high-risk, heavily pretreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Subjects received doses ranging from MOR208 0.3mg/kg to 12mg/kg as an intravenous infusion on days 1, 4, 8, 15 and 22 in cycle one, and on days 1, 8, 15 and 22 in cycle two. Overall response rate by International Working Group on CLL (IWCLL) 2008 criteria was 11%, which utilizes more rigorous CT scan reduction of internal lymph nodes not previously required in older historic studies. Using IWCLL 1996 response criteria resulted in a response rate of 42%. MORE208 was well tolerated and found safe. The most frequent adverse events were mild to moderate infusion reactions usually with the first dose. Based on these results, MorphoSys plans to commence phase II studies of MOR208 in B-cell malignancies in the near future.

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