LUNG CANCER—NON-SMALL CELL METASTATIC 9000 Oral Abstract Session, Mon, 8:00 AM-11:00 AM RELAY: A multinational, double-blind, randomized Phase 3 study of erlotinib (ERL) in combination with ramucirumab (RAM) or placebo (PL) in previously untreated patients with epidermal growth factor receptor mutation-positive (EGFRm) metastatic non-small cell lung cancer (NSCLC). Kazuhiko Nakagawa, Edward B. Garon, Takashi Seto, Makoto Nishio, Santiago Ponce Aix, Chao-Hua Chiu, Keunchil Park, Silvia Novello, Ernest Nadal, Fumio Imamura, Kiyotaka Yoh, Jin-Yuan Shih, Kwok Hung Au, Denis Moro-Sibilot, Sotaro Enatsu, Annamaria H. Zimmermann, Bente Frimodt-Moller, Carla M. Visseren Grul, Martin Reck; Kindai University Hospital, Osaka, Japan; David Geffen School of Medicine, University of California/TRIO-US Network, Los Angeles, CA; National Kyushu Cancer Center, Fukuoka, Japan; Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; Hospital 12 de Octubre, Madrid, Spain; Taipei Veterans General Hospital, Taipei, Taiwan; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Oncology, University of Turin, Orbassano, Italy; Institut Catala ` d’Oncologia, L’Hospitalet, Barcelona, Spain; Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; National Cancer Center Hospital East, Kashiwa, Japan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Queen Elizabeth Hospital, Kowloon, China; Service Hospitalier Universitaire Pneumologie Physiologie Poleˆ Thorax et Vaisseaux Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France; Lilly Research Laboratories Japan, Kobe- shi, Japan; Eli Lilly & Co., Indianapolis, IN; Eli Lilly and Company, Copenhagen, Denmark; Lilly Oncology Europe, Utrecht, Netherlands; LungenClinic, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany Background: Dual blockade of EGFR and VEGFR pathways in EGFRm NSCLC augments anti-tumor efficacy versus (v) EGFR inhibition alone. RELAY (NCT02411448) evaluated efficacy and safety of ERL, an EGFR TKI standard-of-care, plus RAM, a human IgG1 VEGFR2 antagonist, or PL in 1L EGFRm metastatic NSCLC. Methods: Eligibility included untreated metastatic NSCLC pts with Exon 19 deletion (del) or L858R and no CNS metastasis. Randomized (1:1) pts received ERL (150 mg/day) + RAM (10 mg/kg q2w) or ERL + PL, stratified by gender, geographic region (East Asia v other), EGFRm type (Ex19del v L858R) and EGFR testing method (Therascreen/Cobas v other). The primary endpoint was Investigator assessed progression free survival (PFS). Other objectives included ORR, DoR, PFS2, OS, safety, and plasma T790M mutation (Guardant NGS). Results: 449 pts were randomized characteristics were balanced between treatment arms: Asian 77%, Females 63%, Ex19del 54%. RAM + ERL significantly prolonged PFS, DoR, and PFS2 (Table). Grade .=3 TEAEs were greater with RAM (72%) v PL (54%), largely driven by hypertension (24 v 5%, no Gr4); with 1 treatment related on study death (hemothorax) in RAM v 0 PL. EGFR T790M+ rates at progression are forthcoming. Conclusion: RAM + ERL led to superior PFS in 1L EGFRm metastatic NSCLC. Safety was consistent with the established safety profiles of the individual compounds. Clinical trial information: NCT02411448. RAM + ERL (n=224) PL + ERL (n=225) HR (95% CI) p-value PFS 0.591 (0.461 – 0.760) ,0.0001 Median, months (95% CI) 19.4 (15.4 – 21.6) 12.4 (11.0 – 13.5) Censoring rate 46% 30% ORR, % (95% CI) 76.3 (70.8 – 81.9) 74.7 (69.0 – 80.3) 0.7413 Number of responders 171 168 DoR** 0.619 (0.477 – 0.805)* 0.0003* Median, months (95% CI) 18.0 (13.9 – 19.8) 11.1 (9.7 – 12.3) Censoring rate 41% 24% PFS2 0.690 (0.490 – 0.972) 0.0325 Median, months (95% CI) NR NR Censoring rate 73% 65% Interim OS 0.832 (0.532 – 1.303) 0.4209 Median, months (95% CI) NR NR Censoring rate 83% 81% Median follow-up: 20.7 months NR, not reached * unstratified **Ns are based on number of responders from the ITT population © 2019 American Society of Clinical Oncology. Visit abstracts.asco.org and search by abstract for disclosure information. LUNG CANCER—NON-SMALL CELL METASTATIC 9001 Oral Abstract Session, Mon, 8:00 AM-11:00 AM Phase III randomized trial comparing gefitinib to gefitinib with pemetrexed-carboplatin chemotherapy in patients with advanced untreated EGFR mutant non-small cell lung cancer (gef vs gef+C). Vanita Noronha, Amit Joshi, Vijay Maruti Patil, Anuradha Chougule, Abhishek Mahajan, Amit Janu, Nilendu Purandare, Rajiv Kumar, Sucheta More, Supriya Goud, Nandkumar Kadam, Nilesh Daware, Srushti Shah, Akanksha Yadav, Amit Dutt, Vaishakhi Trivedi, Vichitra Behel, Shripad Dinanath Banavali, Kumar Prabhash; Tata Memorial Centre, Mumbai, India; Tata Memorial Hospital, Mumbai, India; Gunvati J Kapoor Medical Relief Charitable Foundation, Mumbai, India; Tata Memorial Center, Mumbai, India; Advanced Centre for Treatment, Research and Education in Cancer, Navi Mumbai, India Background: Standard first-line therapy for EGFR mutant advanced non-small cell lung cancer (NSCLC) is an EGFR-directed oral TKI. We evaluated whether adding pemetrexed-carboplatin to oral TKI would improve outcomes. Methods: Phase III randomized trial in advanced chemotherapy-na¨ıve NSCLC harboring EGFR sensitizing mutation (exon 19, 21 or 18) with performance status (PS) 0 to 2 planned for palliative therapy. Patients were stratified for PS and EGFR mutation and randomly assigned (computer-generated randomization by independent biostatistician) 1:1 to gefitinib 250 mg orally daily (gef) or gefitinib 250 mg orally daily with pemetrexed 500 mg/m2 IV and carboplatin AUC 5 IV every 3 weeks for 4 cycles, followed by maintenance pemetrexed 500 mg/m2 IVevery3weeks(gef+C). Restaging was every 2 to 3 mths; therapy continued until progression or intolerable toxicity. Primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), toxicity and response rate. Survival endpoints were assessed in the intention-to-treat population. Results: Between Aug 2016 and Aug 2018, 350 patients were randomly assigned to gef (n = 177) and gef+C (n = 173). Median age was 54 yrs, 48% were females, 84% never-smokers, 21% were PS 2 and 18% had brain metastases. Median follow-up in surviving patients was 17 months (range, 7 to 30). Radiologic response rates were 81% and 69% in gef+C and gef respectively, P = 0.012. 234 patients (67%) have had events for PFS, 98 in gef+C and 136 in gef. Estimated median PFS was significantly longer with gef+C than gef (16 months, [95% CI, 13.7 to 18.3] vs. 8 months [95% CI, 7.1 to 8.9]; hazard ratio for disease progression or death, 0.5; 95% CI, 0.39 to 0.65; P , 0.001). 120 patients (34%) have died, 42 in gef+C and 78 in gef. Estimated median OS was significantly longer with gef+C than gef (not reached vs. 18 months [95% CI, 14.28 to 21.72]; hazard ratio for death, 0.45; 95% CI, 0.31 to 0.66; P , 0.001). Clinically relevant $ grade 3 toxicities occurred in 51% and 25% of patients in gef+C and gef arms respectively, P , 0.001. Conclusion: Adding pemetrexed-carboplatin chemotherapy to gefitinib significantly prolonged progression free and overall survival but also increased toxicity. Pemetrexed-carboplatin-gefitinib represents a new standard first-line therapy for EGFR mutant NSCLC. Clinical trial information: CTRI/ 2016/08/007149. © 2019 American Society of Clinical Oncology. Visit abstracts.asco.org and search by abstract for disclosure information. LUNG CANCER—NON-SMALL CELL METASTATIC 9002 Oral Abstract Session, Mon, 8:00 AM-11:00 AM ECOG-ACRIN 5508: Pemetrexed, bevacizumab or the combination as maintenance therapy for advanced non-squamous NSCLC. Suresh S. Ramalingam, Suzanne Eleanor Dahlberg, Chandra Prakash Belani, Joel N. Saltzman, Gopakumar S. Nambudiri, John McCann, Jerome D. Winegarden, Mohammed Azher Kassem, Mohamed K. Mohamed, Jan M. Rothman, Alan P. Lyss, Leora Horn, Tom Stinchcombe, Joan H. Schiller, ECOG-ACRIN Cancer Research Group; Winship Cancer Institute, Emory University, Atlanta, GA; Dana-Farber Cancer Institute, Boston, MA; Penn State Hershey Cancer Institute, Hershey, PA; University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH; Health East Cancer Care, Woodbury, MN; Baystate Medcl Ctr, Springfield, MA; Ann Arbor Hem Onc Assocs, Ypsilanti, MI; Mt.Sinai Hosp, Chicago, IL; Cone Health Center at Wesley Long, Greensboro, NC; The Regional Cancer Center, Erie, PA; Missouri Baptist Cancer Ctr, St Louis, MO; Vanderbilt University Medical Center, Nashville, TN; Duke Cancer Institute, Durham, NC; The University of Texas Southwestern Medical Center, Dallas, TX Background: Maintenance therapy is a standard approach for advanced non-squamous NSCLC. Peme- trexed or bevacizumab are considered evidence-based options. The combination of bevacizumab and pemetrexed has been documented to improve progression-free survival (PFS). We conducted a phase 3 study to determine the optimal maintenance therapy for advanced NSCLC. Methods: Patients (pts) with advanced non-squamous NSCLC, no prior systemic therapy, and ECOG performance status 0/1 were treated with carboplatin (AUC = 6), paclitaxel (200 mg/m2) and bevacizumab (15 mg/Kg) every 3 weeks for up to 4 cycles (step 1). Patients with CR/PR/SD after 4 cycles were then randomized 1:1:1 to maintenance therapy with bevacizumab (15 mg/Kg), pemetrexed (500 mg/m2) or the combination of the two agents every 3 weeks until disease progression (step 2). The primary endpoint was overall survival (OS), defined as the time from randomization to death from any cause and censoring defined at the last date of followup. 1495 pts provided 81% power to detect a hazard ratio of 0.75 while controlling the 2- sided type I error at 0.025 for each comparison, assuming approximately 60% of those patients would be randomized. Results: We enrolled 1516 pts to step 1 (male 52%; ECOG PS 1 62%; adenocarcinoma 90%); After induction therapy, 874 (57%) pts were randomized to step 2 (median age 64 yrs; male 49%; ECOG PS 1 55%).