J1281, A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of MPDL3280A Administered Intravenously as a Single Agent to Patients with Locally Advanced or Metastatic Solid Tumors or Hematologic Malignancies
This research is being done to test the safety of the investigational drugMPDL3280A, in people with locally advanced/metastatic solid tumor, malignant lymphoma or multiple myeloma (MM). We also want to find out the best dose of MPDL3280A and what effects, good and/or bad, it has on you and your tumors. The main purposes of this dose expansion phase of the study are to: learn more about the side effects of MPDL3280A, learn whether MPDL3280A can shrink tumors or delay tumor growth, learn whether patients whose tumors express the PD-L1 protein on their surface have a better chance of responding to MPDL3280A with tumor shrinkage or delayed tumor growth, and identify changes in the blood or in tumors that are associated with tumor shrinkage or delayed tumor growth.
Histologically or cytologically documented, incurable or metastatic solid tumor or hematologic malignancy and has completed prescreening tumor characterization that is positive for PD-L1 over-expression. Must have confirmed availability of representative tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report. (If archival tissue is either insufficient or unavailable, the patient may still be eligible, upon discussion with the Medical Monitor, if the patient can provide at least 5 unstained, serial slides or is willing to consent to and undergo a pre-treatment core or excisional biopsy of the tumor).Must have measurable disease with at least 1 unidimensional measurable lesion per RECIST v.1.1.No anti-cancer therapy within 3 weeks prior to starting the study treatment.No prior treatment with anti-CTLA4, antiâ??PD-1, or antiâ??PD-L1 therapeutic antibody or pathway targeting agents.No treatment with systemic immunostimulatory agents (including but not limited to IFN-Î±, interleukin-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1.No treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antiâ??tumor necrosis factor [TNF] agents) within 4 weeks prior to Cycle 1, Day 1.No active autoimmune disease, no active infection.No known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease.
If you qualify to participate in the study following the screening visit, you will be given MPDL3280A once, on Day 1 of Cycle 1. After that cycle, the study doctor will ask you to return to the clinic for at least 15 more visits (Cycles 2 to 16). On Day 1 of each cycle, you may be given MPDL3280A. If your tumor does not grow and you are tolerating MPDL3280A and the other study procedures, you will continue to be given MPDL3280A for up to 12 months.During this study, you will receive a single dose of MPDL3280A by intravenous (IV) infusion every 3 weeks (21 days). You will be given MPDL3280A by IV infusion directly into the blood by inserting a needle into a vein in your arm or a venous access device (a port, for example), and letting MPDL3280A slowly enter your body over about 90 minutes (it can be faster in the next doses). The amount of MPDL3280A given to you will depend on your body weight. You will be watched during the infusion, and if you have any severe side effects (allergic reaction or bronchospasm), your doctor may stop the infusion and treat you as needed. You may also be taken off of the study if the side effects are severe.If your tumor grows larger, you develop new tumors, you choose to leave this research study, or your participation is ended by Johns Hopkins or Genentech for any reason, you will be asked to come to the clinic for a final visit about 30 days after receiving your last dose of MPDL3280A or after the decision was made to stop MPDL3280A.
05/24/2013 04:02 AM