This clinical study is an open-label, non-randomized, multicenter, Phase II safety and efficacy study of the monoclonal antibody CT-011 administered to patients with diffuse large B cell lymphoma (DLBCL), transformed follicular lymphoma, diffuse mixed cell lymphoma or primary mediastinal large cell lymphoma, following autologous peripheral stem cell transplantation (PBSCT). Eligibility criteria require that the lymphoma was determined to be chemosensitive and has not progressed up to 65 days following autologous PBSCT. The study will enroll 80 patients in selected medical centers across the US, Israel and potentially additional countries.

Efficacy endpoints include the effect of CT-011 on progression free survival, the event-free survival and overall survival. Biological and cellular markers will also be assessed.

All final eligible patients will receive an IV infusion of 1.5 mg/kg of CT-011 on Day 1 (60 to 90 days post autologous PBSCT). Treatment will be repeated every 42 days for a total of three courses with treatment visits on Days 1, 43, and 85. CT-011 treatment will be conducted in the outpatient clinic.

The reconstitution of immunologically competent effector cells following autologous PBSCT occurs gradually with the recovery of natural killer (NK) cell numbers and activity culminating within weeks from transplantation. The recovery in the number and function of T cells starts approximately 3 months after transplantation and improves gradually in the months thereafter. Studies conducted in experimental animals and humans suggest that the majority of circulating T cells during the 5 months post transplantation are CD45RO+ cells, the target T-cell population for CT-011.

Administration of CT-011 in this clinical study will be between 2 to 5 months following autologous PBSCT, which corresponds to the time where NK cells have reached optimal activity and reconstitution of T cells has been initiated. Accordingly, it is anticipated that administration of CT-011 during this period will induce immunological response by circulating NK and T cells and lead to further maturation of progenitors of these cells. This activity is hoped to lead to an enhancement of tumor-specific immune response in the study patient population.

For further details on the study and participating centers please go to http://clinicaltrials.gov/ct2/show/NCT00532259

Phase II Study in Patients with Metastatic Colorectal Cancer
The interrelationship between the tumor and the function of immune cells (lymphocytes) at the tumor site in patients with colorectal carcinoma (CRC) is important for generating efficacious and long-lasting anti-tumor immune response. The presence of a certain subset of lymphocytes termed, effector cells, inside the tumor in colorectal cancer has been found to play a central role in the control of tumor recurrence and progression. CT-011 links with PD-1 on effector lymphocytes to extend their survival. Combination of treatments like chemotherapy, that control tumor growth and reduce tumor burden with reagents that overcome escape of immune-system by tumors (like CT-011) is proposed as a promising approach for cancer therapy.

This clinical trial is a multi-center, randomized, open label, active control study in previously untreated patients with metastatic colorectal cancer. The study will evaluate the safety, tolerability and efficacy of the monoclonal antibody, CT-011, administered at 3.0 mg/kg when given in combination with FOLFOX (a combination of folinic acid, 5-fluorouracil and oxaliplatin), the standard chemotherapy regimen for this disease and compare it to treatment by FOLFOX alone. Approximately 168 patients, previously untreated for metastatic colorectal carcinoma are planned to be enrolled in this study. Patients are randomized to one of 2 arms consisting of either CT-011 plus FOLFOX or FOLFOX only.

CT-011 is administered once every 4 weeks for up to a total of 4 administrations. Thereafter, CT-011 is administered approximately every 12 weeks as a maintenance therapy until disease progression or maximum tolerance. Chemotherapy is repeated every 14 days for up to 24 cycles or until disease progression or study discontinuation for any other reason. At the end of FOLFOX therapy, patients who have not progressed are eligible for maintenance chemotherapy by 5FU/leucovorin given at a bi-weekly schedule. For further details on the study and participating centers please go to http://clinicaltrials.gov/ct2/show/NCT00890305.