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Personalized Cancer Vaccines 75 CANCER VACCINES: ONGOING PHASE 3 STUDIES Favld 1 (Favrille; San Diego, CA, U.S.) Favld is an autologous active cancer immunotherapy in which recombinant patient-specific idiotype protein isolated from tumor biopsy is conjugated to keyhole limpet hemocyanin (KLH) and administered in combination with the immunostimulatory factor GM-CSF. Favld is currently undergoing a phase 3 clinical study to determine its ability to extend time to progression (TTP) in patients with follicular B-cell non-Hodgkin’s lymphoma following treatment with Rituxan 1 .The primary end point is disease-free survival at three years. At the time of the prospectively planned interim analysis conducted on 233 out of 349 randomized patients who had been followed for 12 months or more (25), there was no significant difference between FavId-treated and control groups in a secondary end point of response improvement; final data are expected at the end of 2007 (26). MyVax 1 (GTOP; Genitope Corporation, Fremont, CA, U.S.) MyVax personalized immunotherapy is an autologous active cancer immunotherapy consisting of recombinant patient-specific idiotype that is conjugated to KLH, an immunogenic carrier protein, and administered along with GM-CSF adjuvant. Results from a phase 2 study showed that 9 of the 21 patients in the study remained progression-free in their last clinical follow-up at 56 to 78 months following chemotherapy. A pivotal phase 3 study to measure PFS in patients with follicular non-Hodgkin’s lymphoma is underway and scheduled to be completed by December 2007 (27). Stimuvax 1 (Biomira; Edmonton, AB, Canada/Merck KGaA, Darmstadt, Germany) Stimuvax, a non-patient-specific vaccine, consists of a synthetic peptide derived from the tumor-associated antigen MUC-1 encapsulated in a liposome (a phospholipid shell intended to facilitate and improve treatment delivery). It is designed to neutralize the immunosuppressive effect of MUC-1 to better enable the immune system to target the cancer. A phase 2, randomized, open-label trial evaluated Stimuvax in patients with stage IIIB or IV non-small cell lung cancer (NSCLC) whose disease was stable or had responded to treatment following completion of first-line standard chemotherapy, with or without radiation treatment. Final analysis of the trial, which involved 171 patients, showed a survival advantage associated with vaccination for patients with stage IIIB disease (earlier-stage disease and therefore associated with better prognosis; n ¼ 65) but not for patients with stage IV disease (advanced-stage disease, worse prognosis; n ¼ 106) (28,29). In the study, median survival was 30.6 months for stage IIIB patients who received vaccine compared with 13.3 months for stage IIIB patients in the control arm
76 Teofilovici and Wentworth (best supportive care based on current standard clinical practice, which includes palliative radiation therapy and/or second-line chemotherapy). A 1300-patient phase 3 trial has recently launched in patients with stage IIIA or IIIB locoregional NSCLC (30). GSK 1572932A (GlaxoSmithKline; <strong>Ph</strong>iladelphia, PA, U.S.) This cancer immunotherapeutic non-patient-specific vaccine consists of a purified recombinant MAGE-A3 protein combined with GSK’s proprietary adjuvant system. The agent is designed to trigger an immune response against tumor cells expressing MAGE-A3, a tumor-specific antigen expressed on a variety of cancers including NSCLC and melanoma. GlaxoSmithKline has initiated a phase 3, randomized, double-blind placebo-controlled trial of GSK 1572932A as an adjuvant therapy in patients with stage IB, II, or IIIA resectable NSCLC whose tumors express the MAGE-A# antigen. The study will enroll approximately 2270 patients and the primary end point is disease-free survival. GSK 1572932A is used in combination with VaxImmune and QS-21 Stimulon adjuvants (30). THE CONVENTIONAL DRUG DEVELOPMENT MODEL AND DIFFICULTIES APPLYING REGULATORY PROCESS TO CANCER VACCINE DEVELOPMENT The conventional development model for new treatments consists of preclinical and clinical research phases. Preclinical research entails laboratory studies to investigate the basic properties of a drug as well as studies in animals to evaluate the safety and efficacy of a treatment in animal “models” of human diseases. Clinical research is the investigation of an experimental treatment in humans. Clinical trials are designed to answer specific questions about new therapies or new ways of using known treatments. They are used to determine whether a new drug or treatment is both safe and effective, and are only conducted if the preclinical studies have yielded promising results. Before a treatment is approved for marketing, clinical research is typically divided into three phases: phase 1, phase 2, and phase 3. l In phase 1 clinical trials, researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. l In phase 2 clinical trials, the study drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety. l In phase 3 studies, the study drug or treatment is given to large groups of people to further determine its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
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Translational Medicine Series 6 Can
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TRANSLATIONAL MEDICINE SERIES 1. Pr
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Informa Healthcare USA, Inc. 52 Van
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Preface Throughout the last 20 year
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Preface vii Table 1 A Diverse Techn
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Preface . . . . v Contributors . .
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Contributors Pedro Alves Ludwig Ins
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1 Factoring in Antigen Processing i
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Factoring in Antigen Processing in
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7 Multimodality Immunization Approa
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Multimodality Immunization Approach
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8 Bidirectional Bedside Lab Bench P
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Development of Novel Immunotherapeu
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206 Index Antigenic peptides degrad
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208 Index Chromogens, enzymatic act
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210 Index Freund’s adjuvants. See
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212 Index Langerhans cells, 133, 13
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214 Index [Peptide vaccines] invest
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216 Index TCRL. See TCR-like immuno
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Oncology and Immunology about the b
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