Clinical Trials

GDC-0199/ABT-199, also known as RG7601, is a novel small molecule being developed in collaboration with AbbVie and is designed to selectively block the function of Bcl-2 proteins and with the goal of enhancing cell death activity (apoptosis). Bcl-2 proteins play a central role in enhancing cell death activity and are thought to impact tumor formation, growth and resistance. They are expressed at high levels in non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and in other B-cell neoplasms.

* On May 30, 2014, Roche has presented interim results of a phase 1b study for its investigational BCL-2 inhibitor GDC-0199/ABT-199, which is being developed in collaboration with AbbVie, at the ASCO 2014 Annual Meeting. The data showed that GDC-0199/ABT-199 combined with MabThera/Rituxan (rituximab) achieved either a complete response or complete response with incomplete blood count recovery (CR/CRi) rate of 36% in patients with R/R CLL. Importantly, of the patients achieving CR, 75% were free of minimal residual disease (MRD). Additional data will be presented from the global clinical development program of GDC-0199/ABT-199. This includes updated data from the previously reported phase 1 study of GDC-0199/ABT-199 monotherapy in CLL and small lymphocytic lymphoma and new data from a phase 1 study in R/R diffuse large B-cell (DLBCL) and R/R follicular lymphoma (FL) which evaluates the use of higher dosing in these lymphoma settings.

ABT-199 (GDC-0199) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL): High complete-response rate and durable disease control. Poster Presentation, Saturday May 31 during the Leukemia, Myelodysplasia, and Transplantation session (Abstract #7015)

A phase 2 open-label study of the efficacy of ABT-199 (GDC-0199) in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) harboring 17p deletion. (Abstract #TPS7121)

* On June 3, 2013, Roche has announced promising phase 1 data from a study of GDC-0199/ABT-199, also known as RG7601, in people with relapsed /refractory chronic lymphocytic leukemia and relapsed/refractory non-Hodgkin lymphoma. Data were presented at the 49th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. 

In the R/R CLL arm of the study (55 evaluable patients), the investigators concluded that GDC-0199/ABT-199 is highly active achieving an 84% overall response rate. 18% of patients achieved a complete remission (CR) or CR with incomplete count recovery and 65% achieved a partial remission (PR). It is important to note that these results were independent of high-risk markers such as 17p deletion and fludarabine (F)-refractory disease.  In fact, 81% and 78% of patients with 17p deletion and F-refractory CLL, respectively, achieved at least a PR. The most common adverse events (AEs), which occurred in more than 15% of patients, were diarrhea (41%), neutropenia (39%), nausea (38%), fatigue (29%), upper respiratory tract infection (27%), cough (23%) and thrombocytopenia (18%). Grade 3/4 AEs occurring in more than 5 patients were neutropenia (38%), thrombocytopenia (11%) and tumor lysis syndrome (TLS) (11%).  TLS occurred in 3/3 patients in cohort 1 and 2/53 patients with the modified stepped dosing schedule.  One of the modified schedule events was fatal and occurred within 48 hours of dose-escalation to 1200 mg in a patient with laboratory evidence of TLS.

In the R/R NHL arm of the study (32 patients), the investigators concluded that GDC-0199/ABT-199 is highly active, particularly in mantle cell lymphoma (MCL) and that further investigation of GDC-0199/ABT-199 as a single-agent and in combination is warranted. For the 29 patients evaluated for efficacy, the overall response rate was 53%, with 9% experiencing CRs and 44% experiencing PRs.  In mantle cell lymphoma (MCL) the overall response rate was 100%. The most common AEs occurring in 15% of patients or more, were nausea (41%), diarrhea (28%), vomiting (19%), fatigue (19%), pyrexia (19%), cough (19%) and neutropenia, thrombocytopenia, constipation, dyspepsia, back and extremity pain, each in 16% of patients.

The FDA recently accepted Genentech and AbbVie’s amended clinical trial protocols for studies of GDC-0199/ABT-199 in patients with CLL and enrollment for GDC-0199/ABT-199 clinical trials in CLL, NHL and multiple myeloma has been re-instated. Genentech and AbbVie expect to move GDC-0199/ABT-199 into later-stage clinical trials in the near future.