1129TiP - A phase 1b/2, multicenter, open label trial to evaluate the safety and efficacy of talimogene laherparepvec (T-VEC) and ipilimumab (ipi) versus ipi...

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Cancer Immunology and Immunotherapy
Melanoma and other Skin Tumours
Presenter Frances Collichio
Citation Annals of Oncology (2014) 25 (suppl_4): iv374-iv393. 10.1093/annonc/mdu344
Authors F.A. Collichio1, M. Milhem2, R.H. Andtbacka3, I. Puzanov4, Y. Saenger5, J. Chesney6, L. Cranmer7, O. Hamid8, T. Logan9, J. Glaspy10, C. Lebbe11, C. Garbe12, J. Gansert13, A. Li14, J. Chou13, H. Kaufman15
  • 1Department Of Medicine, University of North Carolina Medical Center, 27514 - Chapel Hill/US
  • 2Oncology, University of Iowa Hospitals & Clinics, Iowa City/US
  • 3Surgical Oncology, University of Utah Huntsman Cancer Institute, Salt Lake City/US
  • 4Department Of Hematology/oncology, Vanderbilt University, 37232-6307 - Nashville/US
  • 5Hematology And Medical Oncology, Mount Sinai Medical Center, New York/US
  • 6Department Of Medicine, University of Louisville, Louisville/US
  • 7Melanoma/sarcoma Program, University of Arizona Cancer Center, Tucson/US
  • 8Department Of Medical Oncology, The Angeles Clinic and Research Institute, 90025 - Los Angeles/US
  • 9Simon Cancer Center, Indiana University, Indianapolis/US
  • 10School Of Medicine, University of California at Los Angeles Medical Center, Los Angeles/US
  • 11Dermatology, Hôpital Saint-Louis - APHP CIC Dermatology, 75010 - Paris/FR
  • 12Dermatology, Universitätsklinikum Tübingen, Tubingen/DE
  • 13Global Development, Amgen Inc., Thousand Oaks/US
  • 14Biostatistics, Amgen Inc., Thousand Oaks/US
  • 15Surgical Oncology, Rush University Medical Center, Chicago/US

Abstract

Background

T-VEC is a herpes simplex virus-1 based oncolytic immunotherapy designed to selectively replicate in cancer cells and produce GM-CSF to initiate systemic antitumor immune responses. OPTiM, a phase 3 trial of T-VEC vs GM-CSF in unresected stage IIIB-IV melanoma, met its primary endpoint of higher durable response rate in favor of T-VEC. Objective response rate (ORR) was 26.4% vs 5.7%, with complete response (CR) 10.8% vs 0.7% in favor of T-VEC. Immune checkpoint blockade with ipi improves overall survival (OS) in advanced melanoma. Ipi has a 10-15% ORR with 1-2% CR by immune-related response criteria (irRC). A phase 1b/2 study was designed to evaluate safety and efficacy when T-VEC is added to ipi as a priming regimen (clinicaltrials.gov #NCT01740297). Phase 1b showed the combination was tolerable, and phase 2 opened in Aug 2013.

Trial design

Phase 2 evaluates the efficacy and safety of T-VEC + ipi vs ipi alone in untreated, unresectable stage IIIB-IV melanoma. Approximately 140 patients will be randomized 1:1. The primary endpoint is OS. Secondary endpoints: safety, ORR, time to response, duration of response, progression-free survival, resection rate, 1- and 2-yr survival. Key eligibility criteria: unresectable stage IIIB-IV melanoma naïve to systemic therapy (except adjuvant); ECOG performance status 0-1; measurable disease; ≥1 injectable cutaneous/ subcutaneous/ nodal tumor; no brain metastases; no symptomatic autoimmunity; no immunosuppression; no HIV/HBV/HCV; no antiherpetic therapy. T-VEC is injected into nonvisceral lesions up to 4 × 106 plaque forming units/mL (pfu/mL) on d1, wk 1; up to 4 × 108 pfu/mL d1, wk 4; then q2w. Ipi is dosed 3 mg/kg IV q3w × 4 starting wk 6 with the 3rd T-VEC dose. Treatment with T-VEC continues until all injectable tumors have disappeared, disease progression per irRC, or intolerance. Enrollment began in the USA and is expected to open in France/Germany by Dec 2014. Combining T-VEC and ipi represents a novel immunotherapeutic approach to promote the initiation of antitumor immunity and simultaneously enhance antitumor T-cell responses.

Disclosure

F.A. Collichio: Dr. Collichio has served on an advisory board and received consultant fees from Amgen, Inc. She receives clinical trial research support from Amgen, Novartis, GlaxoSmithKline, Morphotec, and Bristol-Myers Squibb; M. Milhem: Dr. Milhem has participated on advisory boards for Genentech and Amgen, Inc.; R.H. Andtbacka: Dr. Andtbacka has participated in advisory boards for Amgen, Inc.; I. Puzanov: Dr. Puzanov has received honoraria for participation on advisory boards for Amgen, Inc. His institution receives research funding from Amgen, Inc.; Y. Saenger: Dr. Saenger has participated in advisory boards for Amgen, Inc.; J. Chesney: Dr. Chesney has served on an advisory board for Amgen, Inc. O. Hamid: Dr. Hamid has served as a consultant for Amgen, Inc. and has received clinical trials support from Amgen, Inc.; T. Logan: Dr. Logan's institution has received grant money, and writing assistance, medicines, equipment, or administrative support from Amgen, Inc.; J. Glaspy: Dr. Glaspy has served as a consultant to and received research support from Amgen, Inc.; C. Lebbé: Dr. Lebbé has participated in advisory boards for Roche, GlaxoSmithKline, Novartis, Bristol-Myers Squibb, and Amgen, Inc.; J. Gansert: Dr. Gansert is a compensated employee and stockholder of Amgen, Inc.; A. Li: Ai Li is a compensated employee and stockholder of Amgen, Inc.; J. Chou: Dr. Chou is a compensated employee and stockholder of Amgen, Inc.; H. Kaufman: Dr. Kaufman has received honoraria from Amgen, Inc. for participation in advisory boards and has received research funding from Amgen, Inc. for conducting clinical trials. All other authors have declared no conflicts of interest.