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Oncology Advances October 2015

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2 | Oncology Advances Immunotherapy trials at Dana-Farber/Brigham and Women's Cancer Center using PD-1 inhibitors have expanded to include studies for several gastrointestinal cancers and combination studies spanning a wide range of cancers. The Center for Immuno-Oncology at Dana-Farber/Brigham and Women's Cancer Center, led by Director F. Stephen Hodi, Jr., MD, and Clinical Director Patrick A. Ott, MD, PhD, offers more than 20 early phase immunotherapy trials using a variety of approaches. Dr. Hodi and Dr. Ott also collaborate with dis- ease center leaders at Dana-Farber/Brigham and Women's Cancer Center to initiate immunotherapy trials in cancers where immunotherapy has not traditionally been used. A New Approach for Gastrointestinal Cancers The Gastrointestinal Cancer Center at Dana-Farber/Brigham and Women's Cancer Center is currently enrolling patients in a phase II trial of the PD-1 inhibitor pembrolizumab for patients with metastatic gastric or gastroesophageal junction adenocarcinoma who have progressed on at least two prior chemotherapy regimens, including trastuzumab. Charles Fuchs, MD, MPH, Director of the Gastrointestinal Cancer Center, is the site Principal Investigator of this study, which is based on previous demonstration of efficacy in earlier studies of PD-1 inhibition in gastric cancer. For more information re- garding this trial, please contact Christopher Graham, RN, at (617) 632-5960. The Center is expected to open numerous additional trials using pembrolizumab in the fall of 2015, including first line and second line therapy for patients with gastrointestinal cancers. Another study will combine pembrolizumab with ramu- cirumab, a monoclonal antibody VEGFR-2 antagonist that was approved after demonstrating a survival benefit in advanced gastric cancer in a separate study led by Dr. Fuchs (Lancet. 2014 Jan 4;383(9911):31-9.). "Immunotherapy represents an entirely new way to treat gas- trointestinal cancers, but our approach to this treatment is based on scientific evidence of target mutations in these can- cers," said Dr. Fuchs. Genomic Analysis of Gastric Cancer Through The Cancer Genome Atlas (TCGA) program, medical oncologist Adam Bass, MD, co-chaired the largest ever project to map the genomic changes in gastric and esophageal can- cers. A comprehensive genomic analysis of nearly 300 gastric cancers, performed by TCGA researchers, was published in Nature last year (Nature. 2014 Sep 11;513(7517):202-9.). The study showed the amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2) in a subtype PD-1 Inhibitor Trials Target Gastrointestinal Cancers, Span Many Cancer Types in Combination Studies of gastric cancers. An earlier phase study of PD-1 inhibition across a range of cancers also showed specific benefit in pa- tients with gastric cancer. Combination Therapies with PD-1 Inhibitors In the Center for Immuno-Oncology, Dr. Hodi and Dr. Ott are leading several trials that are combining pembrolizumab (and other agents directed at PD-1 or PD-L1) with other therapies for the treatment of a range of cancers in order to assess safety and increase efficacy of treatment for these cancers. The Cen- ter features an immune assessment core for evaluation of pa- tients on current immunotherapies and a pathology core for identification of biomarkers and analysis of immune therapies. Examples of current combination therapy studies in the Center for Immuno-Oncology are: • Phase 1 Trial of MK-3475 Plus Ziv-Aflibercept in Patients With Advanced Solid Tumors – This study, led by interna- tional Principal Investigator F. Stephen Hodi, MD, will ex- amine the side effects and best dose of ziv-aflibercept when given together with pembrolizumab in treating patients with advanced solid tumors, including metastatic melanoma, metastatic renal cell carcinoma, recurrent colorectal cancer, recurrent ovarian cancer, recurrent renal cell carcinoma, stage IV ovarian cancer, stage IVA colorectal cancer, and stage IVB colorectal cancer. For more information regarding this trial, please contact Principal Investigator F. Stephen Hodi, MD, at (617) 632-5053 or; Key features of gastric cancer subtypes. (Nature. 2014 Sep 11; 513(7517):202-9.)

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