Date: 2014-11-06
Type of information: Interim results
phase: 3
Announcement: interim results
Company: GSK (UK) Genmab (Denmark)
Product: ofatumumab (Arzerra®)
Action
mechanism: Ofatumumab is a human monoclonal antibody which targets an epitope on the CD20 molecule encompassing parts of the small and large extracellular loops. It is being developed under a co-development and commercialization agreement between Genmab and GSK. In the USA, ofatumumab is approved for use in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate. In the EU, ofatumumab is approved for use in combination with chlorambucil or bendamustine for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy. Ofatumumab is also approved for first-line use in Russia.
Disease: patients with relapsed chronic lymphocytic leukemia (CLL) who responded to treatment at relapse
Therapeutic area: Cancer - Oncology
Country: Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, Denmark, Finland, France, Greece, Hungary, India, Israel, Italy, Korea, The Netherlands, Norway, Poland, Puerto Rico, Russian Federation, Spain, Sweden, Turkey, Ukraine, USA
Trial
details: Prolong is a phase III, open label, randomized, multicenter trial of ofatumumab maintenance treatment versus no further treatment in subjects with relapsed chronic lymphocytic leukemia who have responded to induction therapy. This pivotal Phase III study was designed to randomize up to 532 patients with relapsed CLL who have responded to treatment at relapse, to either ofatumumab maintenance treatment or no further treatment (observation). Patients in the ofatumumab arm receive an initial dose of 300 mg of ofatumumab, followed one week later by a second dose of 1,000 mg, then doses of 1,000 mg every 8 weeks for up to two years, while patients in the observation treatment arm receive no further treatment. The primary endpoint of the study is PFS. Secondary objectives will evaluate clinical benefit, safety, tolerability, the health-related quality of life of subjects treated with ofatumumab versus no further treatment, and pharmacokinetics among relapsed CLL patients receiving maintenance therapy with ofatumumab. (NCT01039376)
Latest
news: * On November 6, 2014, Genmab announced additional data from the interim analysis of the ofatumumab (Arzerra™) Phase III study, PROLONG (OMB112517). The study evaluated ofatumumab maintenance therapy versus no further treatment (observation) in patients with a complete response (CR) or partial response (PR) after 2nd or 3rd line treatment for chronic lymphocytic leukemia (CLL). The improvement in the study's primary endpoint, progression free survival (PFS), met the prespecified statistical significance level for the interim analysis. A total of 474 patients were included in the interim analysis. Patients who received ofatumumab maintenance treatment lived 13.4 months longer without their disease worsening (median PFS) than patients who received no further treatment. Median PFS was 28.6 months for the ofatumumab treatment arm and 15.2 months for the observation arm (Hazard Ratio 0.48; p<0.0001). * On July 31, 2014, GSK and Genmab announced that an Independent Data Monitoring Committee (IDMC) interim analysis of a Phase III study, PROLONG (OMB 112517), reached the predefined significance level for efficacy (p≤0.001). The interim analysis demonstrated that treatment with ofatumumab (Arzerra™) met the primary endpoint of improving progression free survival (PFS). The study evaluated ofatumumab maintenance therapy versus no further treatment (observation) in patients with relapsed chronic lymphocytic leukemia (CLL) who responded to treatment at relapse.The IDMC did not identify any new safety signals and will continue to monitor patients for safety until all study patients complete therapy. Further analysis of the safety and efficacy data is underway and will be shared with regulators and the scientific community in the coming months. GSK is now looking forward to presenting detailed data from this study at a future medical conference. The group will also share the results of this interim analysis with regulatory agencies to evaluate the potential for future regulatory filings.
The amount of time until patients started their next therapy was significantly longer in the ofatumumab treatment arm than in the observation arm (median 38.0 months vs 27.4 months, Hazard Ratio 0.63; p=0.0076).
There were no unexpected safety findings. Adverse events occurred in 87% of patients in the ofatumumab treatment arm versus 75% in the observation treatment arm. In the ofatumumab treatment arm, 25% of patients experienced grade 3-4 adverse events compared to 17% in the observation arm. Grade 3-4 infections were 18% in the ofatumumab arm and 13% in the observation arm. The two most common grade 3-4 adverse events were neutropenia (22% in ofatumumab arm vs 9% in observation arm), and pneumonia (7% in ofatumumab arm vs 4% in observation arm). The death rate was similar in both arms (14%).
These data will be presented in an oral session at the 56th Annual Meeting of the American Society of Hematology (ASH) in San Francisco, California on December 6 from 12 Noon to 1:30PM PST.
