P-096A Phase 3 Study of Chemotherapy + Pembrolizumab Vs
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abstracts Annals of Oncology (previously known as BGB-290) is a selective PARP1/2 inhibitor that crosses the blood- P À 096 A phase 3 study of chemotherapy 1 pembrolizumab vs brain barrier, has shown potent DNA–PARP trapping, and has demonstrated robust chemotherapy 1 placebo as neoadjuvant/adjuvant treatment for antitumor activity in preclinical models. In early phase clinical studies (NCT02361723; patients with gastric or gastroesophageal junction (G/GEJ) cancer: NCT03333915), pamiparib was generally well tolerated and showed promising antitu- KEYNOTE-585 - Trial in progress mor activity. These studies also established 60 mg orally twice daily as the recom- 1 2 3 4 5 6 7 mended pivotal dose. Y Bang , E Van Cutsem , C Fuchs , A Ohtsu , J Tabernero , D Ilson , W Hyung , V Strong6, T Goetze8, T Yoshikawa9, L Tang6, P Hwang10, K Shitara11 Methods: The purpose of this double-blind, placebo-controlled, randomized, multi- 1 2 center Phase 3 study (NCT03427814) conducted in Asia, Australia, Europe, and North Seoul National University Hospital, Seoul, Republic of Korea, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium, 3Yale Cancer Center, New America is to compare the efficacy, safety, and tolerability of pamiparib with placebo as 4 5 maintenance therapy in 540 patients with advanced gastric cancer who have Haven, Connecticut, USA, National Cancer Center Hospital East, Kashiwa, Japan, Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, Spain, responded to first-line, platinum-based chemotherapy. Patients who are 8 weeks after 6 7 their last platinum dose of first-line chemotherapy will be randomized 1:1 to receive Memorial Sloan Kettering Cancer Center, New York, New York, USA, Yonsei Cancer Hospital, Yonsei University Health System, Seoul, Republic of Korea, 8Institute of Clinical either pamiparib 60 mg twice daily or placebo in 28-day cycles. Patient randomization 9 will be stratified by genomic loss of heterozygosity status (ie, high versus low), region, Cancer Research, UCT University Cancer Center, Frankfort, Germany, Kanagawa Cancer Center, Yokohama, Japan, 10Merck & Co., Inc., Kenilworth, New Jersey, USA, and ECOG status. Radiologic assessments will be centrally evaluated per RECIST every 11 8 weeks after first dose. Safety will be assessed on Day 1 of each cycle, and Day 15 of National Cancer Center Hospital East, Kashiwa-city, Japan Cycles 1 and 2, and as needed. Blood samples will be collected at various time points to determine the pharmacokinetics of pamiparib in inoperable, locally advanced gastric Introduction: Pembrolizumab monotherapy demonstrated promising efficacy and cancer patients. The primary endpoint is progression-free survival; key secondary end- manageable safety patients with advanced metastatic G/GEJ adenocarcinoma who have points include safety/tolerability, overall survival, objective response rates, time and received 2 prior lines of therapy, resulting in FDA approval for patients with PD-L1– duration of response, and time to second subsequent treatment. Correlative biomarker positive tumors (combined positive score [CPS] 1) whose disease progressed on or analyses in tumor tissues and blood will be performed. after 2 prior lines of therapy. When combined with cisplatin and 5-fluorouracil (5- FU), pembrolizumab demonstrated promising efficacy and manageable safety in patients with previously untreated metastatic G/GEJ cancer in the phase 2 KEYNOTE- 059 study. Combining chemotherapy with pembrolizumab in the neoadjuvant/adju- P À 095 A randomized clinical trial of apatinib on an intermittent versus vant setting may be beneficial for patients with locally advanced, resectable G/GEJ can- continuous dosing schedule in combination with docetaxel for cer. KEYNOTE-585 (ClinicalTrials.gov, NCT03221426) is a phase 3, randomized, advanced gastric cancer in second-line setting - Trial in progress double-blind study to evaluate the efficacy and safety of chemotherapy þ pembrolizu- mab versus chemotherapy þ placebo as neoadjuvant/adjuvant treatment for locally Y Yan2,LKe2,XHu3,SWu2, J Niu2,HLi1,HXu1, H Luo1, L Cao1, W Chen1,CJi4, advanced resectable G/GEJ cancer. , G Wang4,TXu4,BHu4 Methods: Key eligibility criteria are age 18 years; previously untreated localized G/ 1Department of Oncology, Anhui Provincial Cancer Hospital, The First Affiliated GEJ adenocarcinoma (Siewert type 2 or 3 tumor; eligibility of Siewert type 1 tumors is Hospital of University of Science and Technology of China, Hefei, China, 2Department limited to those for whom planned treatment is perioperative chemotherapy and resec- of Oncology, Anhui Provincial Cancer Hospital, The First Affiliated Hospital of University tion), defined by T3 or greater primary lesion or the presence of any positive clinical of Science and Technology of China, Hefei, China, 3Department of Oncology, Anhui nodes without evidence of metastatic disease; planned surgery after preoperative che- Provincial Cancer Hospital, The First Affiliated Hospital of University of Science and motherapy; Eastern Cooperative Oncology Group performance status 0/1; adequate Technology of China, Hefei, China, 4The First Affiliated Hospital of USTC, Anhui organ function; no active autoimmune disease. Eligible patients will be randomly Provincial Hospital, Hefei, China assigned in a 1:1 ratio to receive chemotherapy þ pembrolizumab (arm 1) or chemo- therapy þ placebo (arm 2). Patients will receive neoadjuvant (preoperative) chemo- Introduction: Apatinib, a small molecule oral tyrosine kinase inhibitor (TKI) that therapy þ pembrolizumab every 3 weeks (Q3W) for 3 cycles (arm 1) or chemotherapy mainly targets vascular endothelial growth factor receptor-2, has been approved in the þ placebo Q3W for 3 cycles (arm 2) followed by surgery, then adjuvant chemotherapy treatment of advanced gastric cancer in China. Whereas, many patients treated with þ pembrolizumab Q3W for 3 cycles (arm 1) or chemotherapy þ placebo Q3W for 3 apatinib experienced toxicity necessitating dose reduction. Maintaining adequate dos- cycles (arm 2), then monotherapy with pembrolizumab (arm 1) or placebo (arm 2) ing and drug levels are essential for optimizing clinical efficacy. Thus, it is urgently Q3W for 11 cycles; treatment will occur for up to 17 cycles. Chemotherapy is cisplatin needed to explore optimal dosing strategy of apatinib treatment in advanced gastric 80 mg/m 2 IV þ either capecitabine 1000 mg/m 2 orally twice daily or 5-FU 800 mg/m cancer. Other small molecule TKIs such as sunitinib [J Clin Oncol, 27 (22): 3584-3590], 2 IV (investigator’s choice). Pembrolizumab 200 mg was administered IV. In a separate sorafenib [Future Oncol, 13(8): 679-693] and anlotinib [J Hematol Oncol, 9(1): 105] safety cohort, 5-FU 2600 mg/m 2 IV þ docetaxel 50 mg/m 2 IV þ oxaliplatin 85 mg/m have demonstrated efficacy and acceptable tolerability in advanced cancers via an inter- 2IVþ leucovorin 200 mg/m 2 IV every 2 weeks (FLOT) is being evaluated as a potential mittent dosing schedule. The current study was conducted to compare the efficacy and chemotherapy option. If adequate safety is demonstrated, FLOT may be incorporated safety of intermittent (5days on/2 days off schedule) vs continuous apatinib therapy in as a chemotherapy backbone option in the main study. Primary end points are overall combination with docetaxel as second-line treatment for advanced gastric cancer. survival, event-free survival per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), by central review, and pathologic complete response (no invasive Methods: This study is designed as an open-label, randomized clinical trial. To enroll, disease and histologically negative nodes) rate by central review. Secondary end points patients are required to have pathologically or histologically confirmed advanced gas- include safety and tolerability and disease-free survival per RECIST v1.1 by central tric cancer and have experienced treatment failure with first-line chemotherapy. Other review. Adverse events will be graded per National Cancer Institute Common inclusion criteria include 18 years; Eastern Cooperative Oncology Group perform- Terminology Criteria for Adverse Events, version 4.0, and will be monitored for 30 or ance status of 0-2; life expectancy more than 3 months. Eligible patients are randomized 90 days after treatment. Patients will be followed for survival status until death, with- to the treatment arms in a ratio of 1:1. In intermittent dose schedule, patients receive drawal of consent, or study end, whichever occurs first. Planned enrollment is 800 oral apatinib 500 mg/d for 5 days followed by 2 days off treatment. In continuous dose patients in the main study and 60 patients in the safety cohort. arm, patients received oral apatinib 500 mg/d as a continuous daily dosing. Docetaxel 60 mg/m2 is administered intravenously to patients on day 1 in a 21-day cycle in both groups. Treatment is continued until disease progression, intolerable toxicity or with- draw of consent. The primary outcome is progression free survival. The secondary out- P À 097 SIRT therapy with Yttrium-90 resin microspheres in patients with comes include objective response rate, disease control rate, overall survival, quality of liver cirrhosis Child Pugh B7-9 and unresectable nonmetastatic life and safety. Tumor response is assessed according to Response Evaluation Criteria in hepatocellular cancer Solid Tumors guideline version 1.1. The incidence and severity of adverse events are defined by the Common