FDA-AACR Workshop: Immuno-Oncology Drug Development

Transcription

1 Day 1 October 13, 2016 FDA-AACR Workshop: Immuno-Oncology Drug Development Time Session Topics Setting Confirmed Speakers/Panelists 8:00 AM Day 1 Welcome and Introduction Overall goals of the workshop and anticipated deliverables 1 organizer Marc Theoret (FDA) 8:15 AM Basic cancer immunobiology 45 min Suzanne Topalian (Johns Hopkins) 9:00 AM- 11:00 AM (with a break from 9:45 to 10:00 AM following the first 3 speakers) Session I: Considerations in the preclinical evaluation of IO products Overview of pre-clinical evaluation in drug development Regulatory Framework for Nonclinical Evaluation to Support First-in-human Trials Preclinical models challenges for exploring & defining activity of IO products Safety Pharmacological and Toxicological considerations to support first-in-human trials of IO products (animal models, human tissues), for identifying initial starting dose including successful examples. Pre-clinical considerations for combination therapy 6 presentations (15 min each; 1.5 hours) Moderator: Whitney Helms (FDA) 1. Kristina Howard (FDA) 2. Pharma 1: Timothy MacLachlan (Novartis) 3. Pharma 2: David Clarke (Pfizer) 4. Pharma 3: Rod Prell (Genentech) 5. Pharma 4: Alan Korman (BMS) 1. Allen Wensky (FDA) 2. Academia: Janis Taube (Johns Hopkins) 3. Pharma: Danuta Herzyk (Merck) 9:45 AM Break, 15 minutes 11:00 AM Session I Panel Discussion and Q&A Panel discussion with Q/A (30 min) Page 1 of 6

2 11:30 AM Lunch, 60 mins PM Session II: dose-finding and evaluation of immune-mediated adverse events Overview of pre-marketing, clinical safety evaluation in drug development 1 lecturer 15 minutes 12: 45 PM Session II cont d: dose-finding and evaluation of immune-mediated adverse events Unique Dose-finding Considerations: DLT definitions Determining dose-response in the identification of a recommended phase 2 dose Exposure-response considerations (FDA) Optimal biological dosing for IO products IO combination therapies 4 presentations (15-20 minutes each; total 1hr 15min) Moderator: Geoff Kim (FDA) 1. Hong Zhao (FDA) 2. Academia: Mark Ratain (U Chicago) 3. Pharma: Eric Rubin (Merck) 4. Pharma: David Feltquate (BMS) 1. Academia (Vaccines): Samir Khleif (Georgia) 2:00 PM Session II (dose-finding) Panel Discussion and Q&A Panel discussion with Q/A (30 min) 2:30 PM Break, 15 min Page 2 of 6

3 2:45 PM Session II cont d: dose-finding and evaluation of immune-mediated adverse events Identification and Management of Unique Toxicities of IO Products: Unique aspects/considerations for management of unique toxicities of IO products, including immune-mediated adverse events (imaes) Challenges in the reporting of imae / Classification/terminology of imae(ctep) Exploration of biomarkers and risk of imae Examining quality of data capture of toxicities for safety data 6 perspectives from academia, Pharma, NCI, and FDA (15 minutes each; total 1.5 hours ) Moderator: Jedd Wolchok (MSKCC) 1. Diko Kazandjian (FDA) 2. Ke Liu (FDA) 3. Elad Sharon (NCI/CTEP) 4. Academia: David Porter (UPenn) 5. Academia: Mario Sznol (Yale) 6. Pharma: David Berman (Medimmune) 4:15 PM Session II (Unique toxicities) Panel Discussion and Q&A Panel discussion with Q/A (30 min) 4:45 PM 5:00 PM Summarizing remarks, Day 1 End Sessions for Day 1 1 organizer Jedd Wolchok (MSKCC) Page 3 of 6

4 Day 2 - October 14, 2016 Time Session Topics Setting Speakers/Panelists 8:00 AM Day 2 Introduction Introduction to Topics for Day 2 1 organizer Suzanne Topalian (Johns Hopkins) 8:15 AM Session III: Endpoints for IO Products: Considerations of unique efficacy endpoints based on the unique biology of checkpoint inhibitors Regulatory Pathways to Approval --Considerations for Novel Endpoints 1 lecturer, 15 min Maitreyee Hazarika (FDA) 8:30 AM Endpoints used and the challenges in the interpretation of results in current clinical trials 1 lecturer, 30 min Raji Sridhara (FDA) 9:00 AM Statistical Analysis Methods with Nonproportional Hazards 1 lecturer, 30 min Nicholas Latimer (U. Sheffield) 9:30 AM Break, 15 min 9:45 AM Session III cont: Endpoints for IO Products: Considerations of unique efficacy endpoints based on the unique biology of checkpoint inhibitors Traditional Endpoints successes and challenges with IO products Unique(?) challenges and successes in ORR and tumor response based, time-to-event endpoints (e.g., PFS) - Timing, frequency, and length of followup - Characterizing pseudo-progression - Continued treatment beyond disease progression - Disease-specific and IO product specific considerations Overall survival still feasible? IO product combinations minutes each (1 hour total. Moderator: Renzo Canetta (retired from BMS) 1. Academia: Larry Schwartz (Columbia) 2. Academic Statistician: Sumithra Mandrekar (Mayo) 3. Pharma: Axel Hoos (GSK) 1. Shenghui Tang (FDA) Page 4 of 6

5 10:45 AM Session III (Traditional Endpoints) Panel Discussion and Q&A Can traditional endpoints ORR, PFS and OS be used in evaluating IO products? If not, what other endpoints would give a metric for evaluating efficacy of IO product. Panel discussion with Q/A (30 min) 11:15 AM Lunch, 60 minutes 12:15 PM Session III cont: Endpoints for IO Products: Considerations of unique efficacy endpoints based on the unique biology of checkpoint inhibitors Alternate Efficacy Endpoints use of alternate endpoints with IO products Use of immune-related response criteria vs. conventional response criteria (e.g., RECIST 1.1) for ORR and time-to-event endpoints Novel measures of surrogate endpoints to demonstrate anti-tumor activity (e.g., durable response)i Novel measures of endpoints to describe clinical benefit (e.g., milestone survival) Disease specific considerations? optimal time point? Statistical analysis methods for use of nontraditional endpoints Challenges and solutions in using alternate endpoints discussed above as it relates to analysis methods and interpretation Metrics for efficacy measure and interpretation (mean, median, restricted mean, AUC, etc.) 6 presentations (15 min each; 90 min total) Moderator: Marc Theoret (FDA) 1. Sirisha Mushti and Lijun Zhang (FDA) 2. Academia: Antoni Ribas (UCLA) 3. Jan Bogaerts (EORTC) 4. Pharma 1: Keaven Anderson (Merck) 5. Pharma 2: Ram Suresh (BMS) 6. Pharma 3: Dan Chen (Genentech) 1. Kun He (FDA) 1:45 PM Session III (Alternate Endpoints) Panel Discussion and Q&A Panel discussion with Q/A (60 min) 2:45 PM Break, 15 min Page 5 of 6

6 3:00 PM Session IV: Novel Trial Designs Clinical trial design considerations: chemotherapy vs. immunotherapy, incorporation of unique biomarkers, combination products (including outside the box novel designs ) Samples size considerations given the expected delayed effect Design consideration with respect frequency and length of follow-up Design consideration if treated beyond progression by RECIST Specific design consideration when IO is administered in adjuvant/neoadjuvant setting or combined o with chemo o with another IO product Incorporating current and future biomarkers in IO trial designs 4 presentations (15 min each; total 1 hour) Moderator: Raji Sridhara (FDA) 1. NCI: Ed Korn 2. Academia: Lillian Siu (Princess Margaret Cancer Centre) 3. Academia: John Kirkwood (U. Pittsburgh) 4. Pharma: Tai-Tsang Chen (BMS) 1. David Rimm (Yale) 4:00 PM Session IV Panel Discussion and Q&A Panel discussion with Q/A (30 min) 4:30 PM Concluding Remarks 1 organizer Maitreyee Hazarika (FDA) 4:45 PM DEPARTURES Page 6 of 6