Phase Ib study of utomilumab (PF-05082566), a 4-1BB/CD137 agonist, in combination with pembrolizumab (MK-3475) in patients with advanced solid tumors

Clinical Cancer Research

Volumn 23, Issue 18, 2017, Pages 5349-5357

  Tolcher, Anthony W ^a   Sznol, Mario ^b   Hu Lieskovan, Siwen ^c   Papadopoulos, Kyriakos P ^a   Patnaik, Amita ^a   Rasco, Drew W ^a   Di Gravio, Donna ^d   Huang, Bo ^e   Gambhire, Dhiraj ^f   Chen, Ying ^e   Thall, Aron D ^e   Pathan, Nuzhat ^e   Schmidt, Emmett V ^g   Chow, Laura Q M ^h  

^a START Center for Cancer Care   (United States)

^b YALE CANCER CENTER   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d Pfizer Oncology   (United States)

^e PFIZER INC   (United States)

^f Pfizer Ltd   (United States)

^g MERCK RESEARCH LABORATORIES   (United States)

^h UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 12P70; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 6; INTERLEUKIN 8; PEMBROLIZUMAB; TUMOR NECROSIS FACTOR; UTOMILUMAB; ANTINEOPLASTIC AGENT; IMMUNOGLOBULIN G; MONOCLONAL ANTIBODY; PF-05082566; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 9;

ADULT; ADVANCED CANCER; AGED; ANEMIA; AREA UNDER THE CURVE; ARTICLE; CD8+ T LYMPHOCYTE; COHORT ANALYSIS; CONSTIPATION; COUGHING; DECREASED APPETITE; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; FATIGUE; FEMALE; FEVER; HUMAN; HUMAN CELL; MALE; MAXIMUM PLASMA CONCENTRATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; OPEN STUDY; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PRURITUS; RASH; SOLID MALIGNANT NEOPLASM; TIME TO MAXIMUM PLASMA CONCENTRATION; TUMOR IMMUNOGENICITY; UPPER RESPIRATORY TRACT INFECTION; VOMITING; ANTAGONISTS AND INHIBITORS; CANCER STAGING; CLINICAL TRIAL; DIAGNOSTIC IMAGING; DRUG EFFECT; DRUG MONITORING; IMMUNOLOGY; MAXIMUM TOLERATED DOSE; METABOLISM; MIDDLE AGED; MOLECULARLY TARGETED THERAPY; MORTALITY; MULTIMODALITY CANCER THERAPY; NEOPLASM; RETREATMENT; T LYMPHOCYTE SUBPOPULATION; TREATMENT OUTCOME; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; COMBINED MODALITY THERAPY; DIAGNOSTIC IMAGING; DRUG MONITORING; FEMALE; HUMANS; IMMUNOGLOBULIN G; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; MOLECULAR TARGETED THERAPY; NEOPLASM STAGING; NEOPLASMS; RETREATMENT; T-LYMPHOCYTE SUBSETS; TREATMENT OUTCOME; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY, MEMBER 9;

EID: 85029504106     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-17-1243     Document Type: Article

References (29)

1. Pennock GK, Chow LQ. The evolving role of immune checkpoint inhibitors in cancer treatment. Oncologist 2015;20:812–22.
2. West H. Immune checkpoint inhibitors. JAMA Oncol 2015;1:115.
3. Cohen J, Sznol M. Therapeutic combinations of immune-modulating antibodies in melanoma and beyond. Semin Oncol 2015;42:488–94.
4. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. KEYNOTE-006 investigators. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015;372:2521–32.
5. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. KEYNOTE-001 investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015;372:2018–28.
6. Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol 2016;17:956–65.
7. Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, et al. Phase I study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. Clin Cancer Res 2015;21:4286–93.
8. Fisher TS, Kamperschroer C, Oliphant T, Love VA, Lira PD, Doyonnas R, et al. Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity. Cancer Immunol Immunother 2012;61:1721–33.
9. Segal NH, Gopal AK, Bhatia S, Kohrt HE, Levy R, Pishvaian MJ, et al. A phase 1 study of PF-05082566 (anti-4-1BB) in patients with advanced cancer. J Clin Oncol 2014;32 (suppl; abstr 3007).
10. Gopal AK, Bartlett NL, Levy R, Houot R, Smith SD, Segal NH, et al. A phase I study of PF-05082566 (anti-4-1BB) þ rituximab in patients with CD20þ NHL. J Clin Oncol 2015;33 (suppl; abstr 3004).
11. Chen S, Lee LF, Fisher TS, Jessen B, Elliott M, Evering W, et al. Combination of 4-1BB agonist and PD-1 antagonist promotes antitumor effector/memory CD8 T cells in a poorly immunogenic tumor model. Cancer Immunol Res 2015;3:149–60.
12. Wei H, Zhao L, Hellstrom I, Hellstrom KE, Guo Y. Dual targeting of CD137 co-stimulatory and PD-1 co-inhibitory molecules for ovarian cancer immunotherapy. Oncoimmunology 2014;3:e28248.
13. Ascierto PA, Simeone E, Sznol M, Fu YX, Melero I. Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Semin Oncol 2010;37: 508–16.
14. Gros A, Robbins PF, Yao X, Li YF, Turcotte S, Tran E, et al. PD-1 identifies the patient-specific CD8þ tumor-reactive repertoire infiltrating human tumors. J Clin Invest 2014;124:2246–59.
15. Palazon A, Martínez-Forero I, Teijeira A, Morales-Kastresana A, Alfaro C, Sanmamed MF, et al. The HIF-1a hypoxia response in tumor-infiltrating T lymphocytes induces functional CD137 (4-1BB) for immunotherapy. Cancer Discov 2012;2:608–23.
16. Azpilikueta A, Agorreta J, Labiano S, Perez-Gracia JL, Sanchez-Paulete AR, Aznar MA, et al. Successful immunotherapy against a transplantable mouse squamous lung carcinoma with anti-PD-1 and anti-CD137 monoclonal antibodies. J Thorac Oncol 2016;11:524–36.
17. Hirano F, Kaneko K, Tamura H, Dong H, Wang S, Ichikawa M, et al. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 2005;65:1089–96.
18. Cheung YK, Chappell R. Sequential designs for phase 1 clinical trials with late-onset toxicities. Biometrics 2000;56:1177–82.
19. Huang B, Kuan P. Time-to-event continual reassessment method incorporating treatment cycle information with application to an oncology phase I trial. Biom J 2014;6:933–46.
20. Huang B, Bycott P, Talukder E. Novel dose-finding designs and considerations on practical implementations in oncology clinical trials. J Biopharm Stat 2016;27:44–55.
21. Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single-agent anti–programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010;28:3167–75.
22. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015;373:23–34.
23. Antonia SJ, Lopez-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol 2016;17:883–95.
24. Torino F, Corsello SM, Salvatori R. Endocrinological side-effects of immune checkpoint inhibitors. Curr Opin Oncol 2016;28:278–87.
25. Kalemkerian GP, Akerley W, Bogner P, Borghaei H, Chow LQ, Downey RJ, et al. National comprehensive cancer network. Small cell lung cancer. J Natl Compr Canc Netw 2013;11:78–98.
26. Koinis F, Kotsakis A, Georgoulias V. Small cell lung cancer (SCLC): no treatment advances in recent years. Transl Lung Cancer Res 2016;5:39–50.
27. Sharp A, Bhosle J, Abdelraouf F, Popat S, O'Brien M, Yap TA. Development of molecularly targeted agents and immunotherapies in small cell lung cancer. Eur J Cancer 2016;60:26–39.
28. Granata R, Locati L, Licitra L. Therapeutic strategies in the management of patients with metastatic anaplastic thyroid cancer: review of the current literature. Curr Opin Oncol 2013;25:224–8.
29. Cabanillas ME, Zafereo M, Gunn GB, Ferrarotto R. Anaplastic thyroid carcinoma: treatment in the age of molecular targeted therapy. J Oncol Pract 2016;12:511–8.