Anticancer agent – obinutuzumab
A new antibody that may have potential in diseases such as non-Hodgkin’s lymphoma (NHL), obinutuzumab, is being developed by Roche
Rituximab has become a key therapy option for non-Hodgkin’s lymphoma (NHL) and other B-cell malignancies. It is a mouse/human chimeric IgG1 antibody directed against the CD-20 protein on the surface of the B-cells, and while it is successful in many patients with B-cell malignancies, many fail to achieve remission, or relapse once they have.
A new antibody that may have potential in diseases such as NHL, obinutuzumab, is being developed by Roche.1 This humanised murine antibody has modified glycosylation pattern in the antibody’s Fc portion, which increases its binding to immune effector cells.
Several clinical trials have been carried out. In a Phase I/II study, 16 patients with relapsed or refractory indolent NHL were given 50 to 2000mg of the drug as monotherapy on days 1 and 8 of the first cycle, and then day 1 of 21-day cycles 2–8 of the non-randomised dose escalating Phase I part of the trial.2 A complete response was seen in five of the patients, and a partial response in a further four, with no obvious dose-response relationship.
In the Phase II part, 40 patients were given 1600mg in the first cycle followed by 800mg in subsequent cycles, or 400mg for each.3 Of the 18 patients on the lower doses, there was one unconfirmed complete response and four partial responses; in the higher dose group, there were three complete responses plus another that was unconfirmed, and eight partial responses. A higher response was seen at the higher dose.
A Phase II trial has also been carried out to compare the antibody’s activity with that of rituximab.4 A total of 175 patients with relapsed indolent B-cell NHL who had previously responded to rituximab were given four weekly infusions of 1000mg obinutuzumab or 375mg/m2 rituximab. Patients without evidence of progression following this induction therapy were given further doses every two months for up to two years, at the same dose.
At the end of the induction phase, objective responses were seen in 32 of the 74 patients on the new antibody, and in 29 of 75 on rituximab. At the time of this initial analysis, 15 of the obinutuzumab group had progressed, and 13 of those on rituximab. Adverse event profiles were not significantly different between the two groups.
Phase III trials are underway of the antibody in combination with chemotherapy.
references
1. E. Mossner et al. Blood 2010, 115, 4393
2. G.A. Salles et al. 53rd Amer. Soc. Hematol Annu. Meeting 2011 (Dec 10–13, San Diego), Abst 268
3. F. Morschhauser et al. 53rd Amer. Soc. Hematol Annu. Meeting 2011 (Dec 10–13, San Diego), Abst 3655
4. L.H. Sehn et al. 53rd Amer. Soc. Hematol Annu. Meeting 2011 (Dec 10–13, San Diego), Abst 269