A Phase II Study of MK 2206 in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma
Diffuse Large B-cell Lymphoma (DLBCL) is the most frequent subtype of Non-Hodgkin lymphoma
(NHL) around the world, in all age groups.
DLBCL is a curable disease and combination of monoclonal antibody against CD20 (rituximab)
with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) regimen have
improved the prognosis of patients with a 20% increase of the cure rate. For the remaining
patients who are not in complete response and/or who relapse after first line therapy, the
possibility of cure is dramatically reduced.
As PI3K/AKT/mTOR pathway regulates the expression of cyclin D1, c-Myc and Stat3 proteins,
which are involved in the pathogenesis of DLBCL HL), this signalling axis is an emerging
therapeutic target for treatment of DLBCL.
One study has shown that the level of p-Akt is an adverse prognostic feature in DLBCL and is
found in 52% of tumors samples from DLBCL patients.
Given the fact that AKT is overactivated in about to 52% of DLBCL and is considered as a
poor prognosis factor, we postulate that targeting AKT in DLBCL may be an interesting
MK-2206 is an orally selective allosteric inhibitor of AKT developed by MERCK currently
highlighted as a promising therapeutic option for cancer patients and under clinical
development in several Phase 1 trials.
Therefore, we propose to conduct a Phase II study using a two-stage Simon's design with
objective response rate (ORR) as the primary endpoint.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
evaluation of the antitumor activity of MK-2206 in terms of objective response rate (ORR).
the objective response rate (ORR) is measured as per 2007 Cheson international response criteria.
4 months after the first day of treatment.
Hervé Ghesquières, MD
Centre Leon Berard, Lyon, France
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)