GENITOURINARY (NONPROSTATE) CANCER 4500 Oral Abstract Session, Mon, 8:00 AM-11:00 AM Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC): Outcomes in the combined IMDC intermediate/poor risk and sarcomatoid subgroups of the phase 3 KEYNOTE-426 study. Brian I. Rini, Elizabeth R. Plimack, Viktor Stus, Rustem Gafanov, Robert Hawkins, Dmitry Nosov, Frederic Pouliot, Denis Soulieres, Bohuslav Melichar, Ihor Vynnychenko, Sergio Jobim Azevedo, Delphine Borchiellini, Raymond S. McDermott, Jens Bedke, Satoshi Tamada, Shuyan Wan, Rodolfo F. Perini, Mei Chen, Michael B. Atkins, Thomas Powles; Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Fox Chase Cancer Center, Philadelphia, PA; Dnipropetrovsk Medical Academy of Ministry of Health of Ukraine, Dnipro, Ukraine; Russian Scientific Center of Roentgenoradiology, Moscow, Russian Federation; The Christie NHS Foundation Trust, Manchester, United Kingdom; Central Clinical Hospital with Outpatient Clinic, Moscow, Russian Federation; CHU de Quebec ´ and Universite ´ Laval, Quebec City, QC, Canada; Centre Hospitalier de l’Universite ´ de Montreal, ´ Montreal, QC, Canada; Palacky ´ University Medical School and Teaching Hospital, Olomouc, Czech Republic; Sumy State University, Sumy Regional Oncology Center, Sumy, Ukraine; Hospital de Clı´nicas de Porto Alegre, Porto Alegre, Brazil; Centre Antoine Lacassagne, UniversiteC ´ oteˆ d’Azu, Nice, France; Adelaide and Meath Hospital and University College Dublin, Dublin, Ireland; Department of Urology, Eberhard- Karls University Tubingen, ¨ Tubingen, ¨ Germany; Osaka City University Hospital, Osaka, Japan; Merck & Co., Inc., Kenilworth, NJ; Georgetown Lombardi Comprehensive Cancer Center, Washington, DC; Barts Health and the Royal Free NHS Trusts, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom Background: In KEYNOTE-426, pembro + axi significantly improved OS (HR 0.53, P , .0001), PFS (HR 0.69, P = .0001), and ORR (59.3% vs 35.7%, P , .0001) vs sunitinib and had manageable toxicity as first-line therapy for mRCC (NCT02853331). The pembro + axi benefit was observed across all IMDC risk groups and regardless of PD-L1 expression. We present data for the combined intermediate/poor risk group and for patients (pts) with sarcomatoid features. Methods: 861 eligible pts with clear-cell mRCC, no prior systemic therapy for mRCC, and KPS $70 were randomized 1:1 to pembro 200 mg IV Q3W for a maximum of 35 cycles plus axi 5 mg orally BID (N = 432) or sunitinib 50 mg orally QD (4-wk on/2-wk off) (N = 429). Primary endpoints were OS and PFS (RECIST v1.1 by blinded, independent central review [BICR]). ORR (RECIST v1.1 by BICR) was the key secondary endpoint. The intermediate/poor risk group was prespecified; the sarcomatoid group was exploratory. HRs and their 95% CIs were calculated with a Cox proportional hazards model. None of the analyses were multiplicity-controlled. Results: 592 (68.8%) of all randomized pts were of IMDC intermediate/poor risk — 294 in the pembro + axi arm, 298 in the sunitinib arm. Pembro + axi improved OS (HR 0.52, 95% CI 0.37-0.74; 12-mo rate 87.3% vs 71.3%), PFS (HR 0.67, 95% CI 0.53-0.85; median 12.6 vs 8.2 mo), and ORR (55.8% [95% CI 49.9-61.5] vs 29.5% [24.4-35.1]) in pts with intermediate/poor risk; CR rates were 4.8% (95% CI 2.6-7.9) vs 0.7% (0.1-2.4). Of the 578 pts with known status, 105 (18.2%) had sarcomatoid features — 51inthepembro+ axi arm, 54 in the sunitinib arm. Pembro + axi improved OS (HR 0.58, 95% CI 0.21-1.59; 12-mo rate 83.4% vs 79.5%), PFS (HR 0.54, 95% CI 0.29-1.00; mediannotreachedvs8.4mo),andORR(58.8% [95% CI 44.2-72.4] vs 31.5% [19.5-45.6]) in pts with sarcomatoid features; CR rates were 11.8% (95% CI 4.4-23.9) vs 0% (0.0-6.6). Conclusions: Pembro + axi provides benefit in the combined population of pts with IMDC intermediate or poor risk and in pts whose tumors had sarcomatoid features. The observed benefits were consistent with those seen in the total population. Clinical trial information: NCT02853331. © 2019 American Society of Clinical Oncology. Visit abstracts.asco.org and search by abstract for disclosure information. GENITOURINARY (NONPROSTATE) CANCER 4501 Oral Abstract Session, Mon, 8:00 AM-11:00 AM A pilot randomized study evaluating nivolumab (nivo) or nivo + bevacizumab (bev) or nivo + ipilimumab (ipi) in patients with metastatic renal cell carcinoma (MRCC) eligible for cytoreductive nephrectomy, metastasectomy or post-treatment biopsy (Bx). Jianjun Gao, Jose A. Karam, Nizar M. Tannir, Matthew T Campbell, Rebecca Slack Tidwell, Kamran Ahrar, Priya Rao, Chaan S. Ng, Eric Jonasch, Surena F. Matin, Amado J. Zurita, Amishi Yogesh Shah, Yu Shen, Jorge M. Blando, Luis M. Vence, Sreyashi Basu, Hao Zhao, James Patrick Allison, Christopher G. Wood, Padmanee Sharma; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Texas MD Anderson Cancer Center, Houston, TX; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Cytoreductive surgery (CS) including cytoreductive nephrectomy and metastasectomy pro- vides clinical benefits to patients with MRCC. However, CS has not been evaluated in the setting of immune checkpoint (IC) therapy. We performed a pre-surgical/biopsy trial to evaluate biological and clinical activity of nivo +/- (bev or ipi) in patients with MRCC. Methods: In this open-label, randomized trial (NCT02210117), patients with MRCC w/o prior IC therapy and anti-VEGF therapy were randomized 2:3:2 to receive nivo (3mg/kg q2wks x3), nivo + bev (10mg/kg q2wks x3) or nivo + ipi (1mg/kg q3wks x2), followed by CS or Bx, and then nivo maintenance therapy up to 2 yrs. Clinical response per RECIST criteria was assessed at $12 wks. Pre- and post-treatment blood and tumors were obtained for correlative studies. Results: All of 105 patients have been accrued and 104 are evaluable for response. For all patients, best overall response (BOR = complete response [CR] + partial response [PR]) including surgery effect was 55% nivo, 44% nivo + bev, 43% nivo + ipi. Median PFS (95% confidence interval) was 14.5 months (5.5, not reached [NR]) nivo, 7.6 (4.8, 8.9) months nivo + bev, 7.5 (2.0, 12.4) months nivo + ipi. Overall survival (OS) at one year was 86% nivo, 73% nivo + bev, 83% nivo + ipi. Grade 3 or higher toxicities related to therapy were 38% for nivo, 42% for nivo + bev (including 18% hypertension), and 47% for nivo + ipi. For patients with CS, BOR including surgery effect was: 86% nivo, 88% nivo + bev, and 69% nivo + ipi. Median PFS was 17.3 months (6.1, NR) nivo, 7.6 (5.7, 10.3) months nivo + bev, 8.9 (2.9, 23.0) months nivo + ipi. OS at one year was 100% nivo, 94% nivo + bev, 92% nivo + ipi. Median OS has not yet reached with a median follow-up of 24.6 months. Immune and gene profiling analyses demonstrate: 1) tumor infiltrating CD8 T cells correlate with clinical responses to nivo or nivo + bev, but not to nivo + ipi; 2) tumor IFN pathway gene expression correlates with responses; and 3) PD-L1 status, tumor mutation or mutation burden, neoantigens did not correlate with response. Conclusions: ICtherapyplusCSissafeandbeneficial to patients with MRCC and therefore, warrants testing, along with a few correlative biomarkers, in a larger phase 3 trial. Clinical trial information: NCT 02210117. © 2019 American Society of Clinical Oncology. Visit abstracts.asco.org and search by abstract for disclosure information. GENITOURINARY (NONPROSTATE) CANCER 4502 Oral Abstract Session, Mon, 8:00 AM-11:00 AM Randomized, double-blind phase III study of pazopanib versus placebo in patients with metastatic renal cell carcinoma who have no evidence of disease following meta- stasectomy: A trial of the ECOG-ACRIN cancer research group (E2810). Leonard Joseph Appleman, Maneka Puligandla, Sumanta K. Pal, Wayne Harris, Neeraj Agarwal, Brian Addis Costello, Christopher W. Ryan, Michael Pins, Jill Kolesar, Daniel A. Vaena, Rahul Atul Parikh, Mehmood Hashmi, Janice P. Dutcher, Robert S. DiPaola, Naomi B. Haas, Michael Anthony Carducci; UPMC Hillman Cancer Center, Pittsburgh, PA; Dana-Farber Cancer Institute, Boston, MA; City of Hope National Medical Center, Duarte, CA; Emory University School of Medicine, Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA; University of Utah Huntsman Cancer Institute, Salt Lake City, UT; Mayo Clinic, Rochester, MN; Oregon Health & Science University, Knight Cancer Institute, Portland, OR; University of Illinois College of Medicine, Chicago, IL; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City, IA; University of Kansas Cancer Center, Westwood, KS; University of Kansas, Kansas City, KS; Cancer Research Foundation of NY, Bronx, NY; University of Kentucky, Lexington, KY; Penn Medicine Abramson Cancer Center, Philadelphia, PA; Sidney Kimmel Cancer Center At Johns Hopkins, Baltimore, MD Background: Patients with no evidence of disease (NED) after metastasectomy for metastatic renal cell carcinoma (mRCC) are at high risk of recurrence, but no systemic therapy has been shown to benefit this population. Pazopanib is an inhibitor of VEGFR and other kinases that improves progression-free survival in patients with measurable RCC metastatic disease. We performed a randomized, double-blind, placebo- controlled multicenter study to test the hypothesis that pazopanib would improve disease-free survival in patients with mRCC rendered NED after metastasectomy Methods: Patients with NED following meta- stasectomy were randomized 1:1 to receive pazopanib starting at 800 mg daily vs. placebo for 52 weeks. Patients were stratified by 1 vs. 1 site of resected disease, and by disease-free interval # vs. 1year. Clinical assessment for toxicity and patient-reported outcomes were performed every 4 weeks, and restaging scans every 12 weeks.