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Introduction Objective Conclusions Disclosures Abstract 88 Analysis of Patient Screening in the Phase III, International, Randomized, Open-Label APACT Trial Michele Reni,1 Jordan Winter,2 Giampaolo Tortora,3,4 Uwe Pelzer,5 Hanno Riess,5 Heung-Moon Chang,6 Eileen M. O’Reilly,7 Do-Youn Oh,8 Inmaculada C. Alés-Díaz,9 Michele Milella,10 Johanna Bendell,11 Benjamin Garlipp,12 Margaret Tempero,13 Teresa Macarulla,14 Eric Van Cutsem,15 Jordan D. Berlin,16 David Goldstein,17 Brian Lu,18 Julie Jeanes,18 Philip Philip19 1IRCCS Ospedale San Raffaele, Milan, Italy; 2University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 3Azienda Ospedaliera Universitaria, Verona, Italy; 4Fondazione Policlinico Universitario Gemelli, IRCCS, Rome, Italy; 5Charité-Universitätsmedizin Berlin, Berlin, Germany; Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany; 6Asan Medical Center, Seoul, South Korea; 7Memorial Sloan Kettering Cancer Center, New York City, NY, USA; 8Seoul National University Hospital, Seoul, South Korea; 9Servicio de Oncología Médica, Hospital Regional Universitario, Malaga, Spain; 10Section of Oncology, Department of Medicine, University of Verona School of Medicine - Verona University Hospital Trust, Verona, Italy; 11Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, USA; 12Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany; 13University of California, San Francisco, Helen Diller Comprehensive Cancer Center, San Francisco, CA, USA; 14Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; 15University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium; 16Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; 17Nelune Cancer Centre, Prince of Wales Hospital, University of New South Wales, Randwick, NSW, Australia; 18Celgene Corporation, Summit, NJ, USA; 19Karmanos Cancer Institute, Detroit, MI, USA INTRODUCTION OBJECTIVE RESULTS • Pancreatic cancer (PC) is associated with a poor prognosis • Evaluate the process for patient identification and reasons Screening and has the lowest survival rate among all cancers1 for exclusion in the APACT trial • Overall, 1226 patients were screened for eligibility • The 5-year survival rate is < 10% for all stages of PC • 360 (29%) were excluded during screening combined1 • Collectively, the most common reason for exclusion was due - This reflects the advanced stage of most diagnoses METHODS to evidence of either potential residual or metastatic disease • Presently, surgical resection is the only potentially curative • During the screening period, patients were assessed by CT (≥ 17% of screened patients; Tables 1 and 2) option for patients with PC or MRI scan performed within 14 days prior to randomization - Those who undergo complete resection, chemotherapy, Table 1. Inclusion Criteria Failed - A patient may have had ≥ 1 reason for exclusion and radiation have a 5-year survival of only 20%2 All Screened Patients • Treatment was to be started within 12 weeks postsurgery Inclusion criteria failed, n (%) • The phase III, international, open-label APACT trial N = 1226 • Patients were randomized once they recovered from surgery CA19-9 < 100 U/mLa 125 (10) assessed the efficacy and safety of nab®-paclitaxel plus and all inclusion/exclusion criteria were met Acceptable blood chemistryb 45 (4) gemcitabine vs gemcitabine alone (Figure 1) in treatment- Pancreatic cancer surgical stagingc 37 (3) • Patients returned within 3 days of randomization to begin Ability to adhere to study visit schedule and naive patients with surgically resected PC 13 (1) cycle 1 dosing other protocol requirements ® nab is a registered trademark of Celgene Corporation. Histologically confirmed PC with complete 12 (1) resectiond Acceptable hematology parameterse 9 (1) Patient ability to start treatment ≤ 12 weeks 7 (1) STUDY DESIGN postsurgery Figure 1. Study Design for APACT ECOG PS ≤ 1 2 (< 1) Acceptable coagulation studiesf 2 (< 1) ClinicalTrials.gov: NCT01964430 Understand and voluntarily sign informed 2 (< 1) consent a Assessed ≤ 14 days after randomization. b Includes AST/ALT ≤ 2.5 × ULN, total bilirubin ≤ ULN, alkaline Screening phosphatase ≤ 2.5 × ULN, serum creatinine ≤ ULN or calculated clearance ≥ 50 mL/min/1.73 m2. c Acceptable staging included T1-3, N0-1, M0. d Complete resection defined as R0 or R1. e Includes ANC N = 1226 ≥ 1500/mm3, platelet count ≥ 100,000/mm3, and hemoglobin ≥ 9 g/dL. f Demonstrated by PT or INR and PTT within normal limits (± 15%). Table 2. Exclusion Criteria Met Key Inclusion Criteria All Screened Patients Key Exclusion Criteria Exclusion criteria met, n (%) • Age ≥ 18 years N = 1226 • Prior neoadjuvant treatment, radiation therapy, or systemic Presence/history of MPC 81 (7) • Histologically confirmed pancreatic adenocarcinoma with R0 therapy for pancreatic adenocarcinoma Unwillingness/inability to comply with study 28 (2) protocol or R1 resection Presence or history of metastatic or locally recurrent • Any significant medical condition, laboratory 11 (1) • ECOG PS ≤ 1 pancreatic adenocarcinoma abnormality, or psychiatric illness Any other malignancy within 5 years of • Acceptable hematology parameters • Any significant medical condition 9 (1) randomizationa • Acceptable blood chemistry levels • Any other malignancy within 5 years prior to randomization Serious medical risk factors involving any major 9 (1) organ systems or serious psychiatric disorders • Surgical staging: T1-3, N0-1, M0 • Active, uncontrolled bacterial, viral, or fungal infections Prior neoadjuvant treatment for PC 2 (< 1) • CA19-9 < 100 U/mL within 14 days of randomization requiring systemic therapy Active infections requiring systemic therapy 2 (< 1) Enrollment in any other clinical protocol or investigational study with an interventional agent 2 (< 1) that may interfere with the study Any conditions that confound the ability to 866 Patients Randomized 1:1 2 (< 1) interpret data Known history of HIV infection or active hepatitis 1 (< 1) B or Cb Any condition, including the presence of laboratory abnormalities, that places the patient 1 (< 1) at unacceptable risk if they were to participate in the study a a Excludes adequately treated in situ carcinoma of the cervix, uterus, or nonmelanomatous skin cancer with Arm A b Arm Ba treatments completed 6 months prior to this study. Includes patients who are currently serologically positive nab-Paclitaxel 125 mg/m2 qw 3/4 + with evidence of prior or signs of active chronic hepatitis. Gemcitabine 1000 mg/m2 qw 3/4 Gemcitabine 1000 mg/m2 qw 3/4 ×6 cycles ×6 cycles CONCLUSIONS • 29% of screened patients were deemed ineligible for inclusion in the APACT trial • The screening process in APACT provided information regarding postsurgical residual disease and ability to start adjuvant therapy Follow-Up • CT scans within 2 weeks of randomization and a CA19-9 Radiological evaluation for up to 5 years after last dose or until recurrence, new cancer therapy, or death threshold of < 100 U/mL identified and excluded patients Safety assessment for 28 days after last dose with residual/metastatic disease (≥ 17% of patients who were screened), which allowed selection of a “true” adjuvant a Stratified by resection status (R0 vs R1), lymph node status (lymph node positive vs negative), and geographic region (North America, Europe and Australia vs Asia Pacific). population - Stringent selection criteria allow patients to receive ENDPOINTS treatment most appropriate for the stage of their disease • CA19-9 threshold and CT scans are strongly recommended Primary Exploratory after surgery before deciding on systemic therapy • Independently assessed disease-free survival • Molecular profiling of tumor tissue DISCLOSURES • Identification of tumor nucleic acids from blood Secondary MR: grants, personal fees, and non-financial support, Celgene; personal fees, Baxalta; personal fees, Shire; personal fees, Eli-Lilly; personal fees, Pfizer; personal fees, Novocure; personal fees, Novartis; other, AstraZeneca; other, Boston Pharmaceutics; JW, GT, IAD, UP: Nothing to disclose; HR: Consulting/Advisory Role, Bayer, Boehringer-Ingelheim, Bristol-Myers-Squibb, Celgene, Daiichi-Sankyo, Johnson & Johnson, Pfizer; Speakers • Overall survival and safety and tolerability • Quality of life Bureau, Bayer, Boehringer-Ingelheim, Bristol-Myers-Squibb, Celgene, Daiichi-Sankyo, Leo-Pharma, Pfizer; Research funding, Bayer, Celgene, Leo Pharma; HMC: Research Funding, Celgene, Pharmacyclics LLC, Senhwa Biosciences, Halozyme INC, Taiho Oncology INC; EMO: Research funding and honoraria, Celgene; DYO: Research funding, AstraZeneca, Novartis, Array, Eli Lilly, Green Cross; Consulting/Advisory role, AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN; MM: Advisory board, Pfizer; Speakers fee, AstraZeneca, EUSA Pharma; JB: Consulting or Advisory Role and research funding, Amgen, Apexigen, Arch Oncology, ARMO BioSciences, Array BioPharma, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Cerulean Pharma, Continuum Clinical, Cyteir, Daiichi Sankyo, EMD Serono, Five Prime Therapeutics, FORMA Therapeutics, Genentech/Roche, Gilead Sciences, GlaxoSmithKline, Incyte, Innate Pharma, Ipsen, ACKNOWLEDGMENTS REFERENCES Janssen, Leap Therapeutics, Lilly, Macrogenics, MedImmune, Merck, Merrimack, Moderna Therapeutics, Molecular Partners, Novartis, Oncogenex, OncoMed, Phoenix Biotech, Prelude Therapeutics, Sanofi, Seattle Genetics, Taiho Pharmaceutical, Tanabe Research, TD2, TG Therapeutics, Tizona
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