Members of the Earle A. Chiles Research Institute Garner Spotlight of ASCO and National Media

June 21, 2017
urba_feb_2015
Walter J. Urba, M.D., Ph.D.,
member, director and endowed chair, Earle A. Chiles Research Institute, Providence Cancer Center

The Earle A. Chiles Research Institute, a division of Providence Cancer Center in Portland, Ore., was well-represented at the 2017 annual meeting of the American Society of Clinical Oncology held June 2-6 in Chicago, Ill. Attendance at this highly anticipated event has grown annually, attributable in part to recent progress in immunotherapy for patients with cancer. More than twenty abstracts with original contributions by EACRI members were selected for presentation or publication at ASCO. Of note, Rachel E. Sanborn, M.D., associate member and co-director of the Providence Thoracic Oncology Program, was invited to present in an oral abstract session on “Clinical results with combination of anti-CD27 agonist antibody, varlilumab, with anti-PD-1 antibody nivolumab in advanced cancer patients.” Additionally, Brendan D. Curti, M.D., member and director of the Cytokine and Adoptive Immunotherapy Program, was first author on the abstract entitled “Activity of a novel immunotherapy combination of intralesional Coxsackievirus A21 and systemic ipilimumab in advanced melanoma patients previously treated with anti-PD-1 blockade therapy,” and Todd S. Crocenzi, M.D., associate member and director of Gastrointestinal Oncology Research, was first author on the abstract entitled “Nivolumab in sorafenib-naive and -experienced patients with advanced hepatocellular carcinoma: CheckMate 040 study.” Both abstracts were selected for poster discussion sessions, and the complete list of abstracts with contributions by EACRI members is listed below.

Another research highlight garnering national media attention is the publication of a clinical study in patients with solid tumors who share similar gene mutations. In the Science article, “Mismatch-repair (MMR) deficiency predicts response of solid tumors to PD-1 blockade” co-authored by Dr. Crocenzi in collaboration with Johns Hopkins University and others, the authors report that patients with advanced MMR-deficient cancers showed increased responsiveness to PD-1 blockade regardless of tumor histology. The results provide an update to the authors’ previous work on colorectal cancer and extended their observation to include other tumor types, such as cholangiocarcinoma and endometrial and gastroesophageal cancers, among others.  The study was featured in an article by the New York Times which provided further commentary on the clinical results and interviews with study participants. Results from this study led the U.S. Food and Drug Administration to approve pembrolizumab for patients with MMR-deficient advanced cancer, marking the first instance of drug approval based on a molecular marker irrespective of tumor site of origin. 

These publications demonstrate the continued leadership by EACRI members in advancing state-of-the-art therapies for cancer patients. Yet the fact remains that only a minority of patients respond to therapy despite significant breakthroughs seen in recent years. Much work remains in the areas of basic science discovery and translational research to develop more effective therapies for all cancer patients. We remain poised to continue our important contributions to the field of cancer immunotherapy, and we invite you to partner with us. Visit chilesresearch.org to learn about our history of pioneering translational immunotherapy research, sign up for a scientist-led tour of our institute, and discover how you can support the development of more effective immunotherapies for cancer patients. Together, we can finish cancer.

Contributions by EACRI members to ASCO 2017 annual meeting abstracts:

  1. A genetic risk-stratified, randomized phase 2 intergroup study of fludarabine/antibody combinations in symptomatic, untreated chronic lymphocytic leukemia (CLL): Results from Cancer and Leukemia Group B (CALGB) 10404 (Alliance). AS Ruppert, JC Byrd, NA Heerema, MR Smith, JE Godwin, S Couban, TA Fehniger, M Thirman, AE Halvorson, MS Tallman, FR Appelbaum, RM Stone, S Robinson, JE Chang, SJ Mandrekar, RA Larson. J Clin Oncol 35, 2017 (suppl; abstr 7503)
  2. A phase I, first-in-human study of MGD006/S80880 (CD123 x CD3 DART) in AML/MDS. N Vey, JK Davidson-Moncada, GL Uy, D Rizzieri, HJ Khoury, MC Foster, JE Godwin, MS Topp, G Martinelli, F Ciceri, MG Carrabba, GA Huls, A Wegener, KC Tran, M Shannon, J Sun, JM Wigginton, JF DiPersio. J Clin Oncol 35, 2017 (suppl; abstr TPS7070)
  3. A phase 1 study to evaluate the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity of the OX40 agonist MEDI0562 in combination with tremelimumab or durvalumab in adult subjects with advanced solid tumors. BD Curti, TM Bauer, N Steeghs, AC Lockhart, FJ Giles, JD Powderly, NA Rizvi, JW Goldman, S Khleif, MJ Gribbin, JT McDevitt, SA Hammond, VL Chiou, A Marabelle. J Clin Oncol 35, 2017 (suppl; abstr TPS3100)
  4. A phase 1/2 study of a novel IL-2 cytokine, NKTR-214, and nivolumab in patients with select locally advanced or metastatic solid tumors. A Diab, NM Tannir, C Bernatchez, CL Haymaker, SE Bentebibel, BD Curti, MKK Wong, I Gergel, MA Tagliaferri, J Zalevsky, U Hoch, S Aung, M Imperiale, DC Cho, SS Tykodi, I Puzanov, HM Kluger, ME Hurwitz, P Hwu, M Sznol. J Clin Oncol 35, 2017 (suppl; abstr e14040)
  5. A phase I/II study of pembrolizumab (P) with gemcitabine (G) in patients (Pts) with previously-treated advanced non-small cell lung cancer (NSCLC): Phase I safety results. RE Sanborn, RM Duffy, BK Fisher, KS Perlewitz, WL Redmond, Y Koguchi, BA Fox. J Clin Oncol 35, 2017 (suppl; abstr e20605)
  6. Activity of a novel immunotherapy combination of intralesional Coxsackievirus A21 and systemic ipilimumab in advanced melanoma patients previously treated with anti-PD1 blockade therapy. BD Curti, JM Richards, S Hallmeyer, MB Faries, RHI Andtbacka, GA Daniels, M Grose, D Shafren. J Clin Oncol 35, 2017 (suppl; abstr 3014)
  7. An open-label, multicohort, phase I/II study to evaluate nivolumab in patients with virus-associated tumors (CheckMate 358): Efficacy and safety in recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). JP Delord, A Hollebecque, JP De Boer, J De Greve, JH Machiels, RS Leidner, RL Ferris, S Rao, I Soumaoro, ZA Cao, H Kang, SL Topalian. J Clin Oncol 35, 2017 (suppl; abstr 6025)
  8. An open-label, single-arm, multi-institutional phase II trial of avelumab for recurrent, metastatic nasopharyngeal carcinoma. AG Sacco, K Messer, RS Leidner, AD Colevas, JJ Nieva, NG Chau, CS Nangia, B Pinsky, KA Gold, GA Daniels, EEW Cohen. J Clin Oncol 35, 2017 (suppl; abstr TPS6092)
  9. Association of improved survival (OS) and tumor control (TC) with interleukin-2 (IL2) with development of immune-related events (IREs): Data from the PROCLAIMSM registry. BD Curti, GA Daniels, DF McDermott, J Clark, H Kaufman, J Singh, M Kaur, TL Luna, NC Gregory, H Hua, M Morse, MKK Wong, JP Dutcher. J Clin Oncol 35, 2017 (suppl; abstr 9528)
  10. Cancer-related fatigue in breast cancer survivors: A longitudinal analysis compared to matched controls. AL Williams, CE Heckler, CL Paterson, DL Barton, KL Young, AK Conlin, LR Weiselberg, KM Mustian, LJ Peppone, MC Janelsins. J Clin Oncol 35, 2017 (suppl; abstr 10045)
  11. Clinical results with combination of anti-CD27 agonist antibody, varlilumab, with anti-PD1 antibody nivolumab in advanced cancer patients. RE Sanborn, MJ Pishvaian, HM Kluger, MK Callahan, AM Weise, J Lutzky, MJ Yellin, T Rawls, L Vitale, A Halim, T Keler, T Davis, NA Rizvi. J Clin Oncol 35, 2017 (suppl; abstr 3007)
  12. Effect of exercise on quality of life (QoL) in 198 older patients with cancer: A URCC NCORP nationwide RCT. KP Loh, SG Mohile, C Cole, C Fung, RF Dunne, PJ Lin, JK Cho, AK Conlin, JP Kuebler, KM Mustian. J Clin Oncol 35, 2017 (suppl; abstr 10019)
  13. Efficacy of single administration of tumor-infiltrating lymphocytes (TIL) in heavily pretreated patients with metastatic melanoma following checkpoint therapy. A Sarnaik, HM Kluger, JA Chesney, J Sethuraman, A Veerapathran, M Simpson-Abelson, MT Lotze, B Larsen, SA Fischkoff, S Suzuki, L Wang, M Mirgoli, M Fardis, BD Curti. J Clin Oncol 35, 2017 (suppl; abstr 3045)
  14. Initial efficacy of anti-lymphocyte activation gene-3 (anti–LAG-3; BMS-986016) in combination with nivolumab (nivo) in pts with melanoma (MEL) previously treated with anti–PD-1/PD-L1 therapy. PA Ascierto, I Melero, S Bhatia, P Bono, RE Sanborn, EJ Lipson, MK Callahan, T Gajewski, CA Gomez-Roca, FS Hodi, G Curigliano, M Nyakas, M Preusser, Y Koguchi, M Maurer, R Clynes, P Mitra, S Suryawanshi, E Muñoz-Couselo. J Clin Oncol 35, 2017 (suppl; abstr 9520)
  15. Keynote-200 phase 1b: A novel combination study of intravenously delivered coxsackievirus A21 and pembrolizumab in advanced cancer patients. HS Pandha, C Ralph, K Harrington, BD Curti, RE Sanborn, WL Akerley, S Gupta, CM Rudin, JE Rosenberg, DR Kaufman, EV Schmidt, M Grose, D Shafren. J Clin Oncol 35, 2017 (suppl; abstr TPS3108)
  16. Long-term (LT) disease-free survival (DFS) of melanoma (MM) and renal cell cancer (RCC) patients following high-dose interleukin-2 (HD IL2). J Clark, BD Curti, EJ Davis, H Kaufman, A Amin, AS Alva, DB Johnson, RL White, PH Wiernik, JP Dutcher. J Clin Oncol 35, 2017 (suppl; abstr e21005)
  17. Nivolumab (nivo) in sorafenib (sor)-naive and -experienced pts with advanced hepatocellular carcinoma (HCC): CheckMate 040 study. TS Crocenzi, AB El-Khoueiry, TC Yau, I Melero, B Sangro, M Kudo, C Hsu, J Trojan, TY Kim, SP Choo, T Meyer, YK Kang, W Yeo, A Chopra, A Baakili, CM Dela Cruz, L Lang, J Neely, T Welling. J Clin Oncol 35, 2017 (suppl; abstr 4013)
  18. Preliminary correlative analysis of PD-L1 expression from the SUNRISE study. NL Kallinteris, RE Sanborn, L Horn, DE Gerber, RB Natale, M Tang, S Downing, A Clement, T Guennel, J Shan, C Hoyt. J Clin Oncol 35, 2017 (suppl; abstr 11603)
  19. Safety and clinical activity of durvalumab monotherapy in patients with hepatocellular carcinoma (HCC). ZA Wainberg, NH Segal, D Jaeger, KH Lee, J Marshall, SJ Antonia, M Butler, RE Sanborn, JJ Nemunaitis, CA Carlson, RS Finn, X Jin, J Antal, AK Gupta, C Massard. J Clin Oncol 35, 2017 (suppl; abstr 4071)
  20. SWOG S1221: A phase 1 dose escalation study co-targeting MAPK-dependent and MAPK-independent BRAF inhibitor resistance in BRAF mutant advanced solid tumors with dabrafenib, trametinib, and GSK2141795 (ClinicalTrials.gov NCT01902173). AP Algazi, J Moon, B Chmielowski, R Lo, KL Kendra, CD Lao, KD Lewis, R Gonzalez, K Kim, JE Godwin, BD Curti, M Othus, A Ribas. J Clin Oncol 35, 2017 (suppl; abstr 2578)
  21. T cell population expansion in response to allogeneic cancer vaccine alone (DPV-001) or with granulocyte-macrophage colony-stimulating factor (GM-CSF) or imiquimod (I) for definitively-treated stage III NSCLC patients (pts). BA Fox, BC Boulmay, R Li, KT Happel, C Paustian, TL Moudgil, S Puri, C Dubay, Y Koguchi, A Mehta, F Lund-Johansen, BK Fisher, WL Redmond, CB Bifulco, A Ochoa, HM Hu, T Hilton, WJ Urba, RE Sanborn. J Clin Oncol 35, 2017 (suppl; abstr e14639)