Literature DB >> 24894651

Phase 2, open-label, 1:1 randomized controlled trial exploring the efficacy of EMD 1201081 in combination with cetuximab in second-line cetuximab-naïve patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

A Ruzsa1, M Sen, M Evans, L W Lee, K Hideghety, S Rottey, P Klimak, P Holeckova, J Fayette, T Csoszi, J Erfan, U Forssmann, T Goddemeier, A Bexon, C Nutting.   

Abstract

AIM: To determine whether EMD 1201081, a TLR9 agonist, added to cetuximab had antitumor activity in second-line recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
METHODS: This was a phase 2, open-label, randomized trial of EMD 1201081 0.32 mg/kg subcutaneously weekly plus cetuximab (combination) vs cetuximab monotherapy (control) in cetuximab-naïve patients with R/M SCCHN who progressed on 1 cytotoxic regimen. Crossover to combination was permitted after progression.
RESULTS: Objective response rate in both arms was 5.7% (95% CI 1.2-15.7%) by independent assessment. Disease control was 37.7% for patients on combination (24.8-52.1%) and 43.4% on control (29.8-57.7%). Neither independent nor investigator assessments showed significant differences between study arms. Median progression-free survival was 1.5 months (1.3-2.6) for patients on combination, and 1.9 months (1.5-2.9) on control. The most frequent adverse events in the combination arm were rash (29.6%), acneiform dermatitis (22.2%), and injection site reactions (20.4%). Grade 3/4 dyspnea and hypokalemia were more frequent with cetuximab monotherapy (7.5% and 5.7% vs 1.9% each, respectively), and grade 3/4 respiratory failure and disease progression were more frequent with combination (5.6% each vs 1.9% each).
CONCLUSION: EMD 1201081 was well tolerated combined with cetuximab, but there was no incremental clinical efficacy.

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Year:  2014        PMID: 24894651     DOI: 10.1007/s10637-014-0117-2

Source DB:  PubMed          Journal:  Invest New Drugs        ISSN: 0167-6997            Impact factor:   3.850


  18 in total

1.  New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada.

Authors:  P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther
Journal:  J Natl Cancer Inst       Date:  2000-02-02       Impact factor: 13.506

2.  Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck.

Authors:  Jay S Cooper; Thomas F Pajak; Arlene A Forastiere; John Jacobs; Bruce H Campbell; Scott B Saxman; Julie A Kish; Harold E Kim; Anthony J Cmelak; Marvin Rotman; Mitchell Machtay; John F Ensley; K S Clifford Chao; Christopher J Schultz; Nancy Lee; Karen K Fu
Journal:  N Engl J Med       Date:  2004-05-06       Impact factor: 91.245

Review 3.  Toll-like receptors in innate immunity.

Authors:  Kiyoshi Takeda; Shizuo Akira
Journal:  Int Immunol       Date:  2005-01       Impact factor: 4.823

4.  Immunology. Targeting the tolls.

Authors:  Ingrid Wickelgren
Journal:  Science       Date:  2006-04-14       Impact factor: 47.728

5.  Novel toll-like receptor 9 agonist induces epidermal growth factor receptor (EGFR) inhibition and synergistic antitumor activity with EGFR inhibitors.

Authors:  Vincenzo Damiano; Rosa Caputo; Roberto Bianco; Francesco P D'Armiento; Antonio Leonardi; Sabino De Placido; A Raffaele Bianco; Sudhir Agrawal; Fortunato Ciardiello; Giampaolo Tortora
Journal:  Clin Cancer Res       Date:  2006-01-15       Impact factor: 12.531

6.  A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer.

Authors:  C Manegold; N van Zandwijk; A Szczesna; P Zatloukal; J S K Au; M Blasinska-Morawiec; P Serwatowski; M Krzakowski; J Jassem; E H Tan; R J Benner; A Ingrosso; S J Meech; D Readett; N Thatcher
Journal:  Ann Oncol       Date:  2011-04-04       Impact factor: 32.976

7.  Phase Ib trial of the Toll-like receptor 9 agonist IMO-2055 in combination with 5-fluorouracil, cisplatin, and cetuximab as first-line palliative treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck.

Authors:  Jean-Pascal Machiels; Marie-Christine Kaminsky; Ulrich Keller; Tim H Brümmendorf; Thomas Goddemeier; Ulf Forssmann; Jean-Pierre Delord
Journal:  Invest New Drugs       Date:  2013-02-10       Impact factor: 3.850

8.  Randomized phase II trial of a toll-like receptor 9 agonist oligodeoxynucleotide, PF-3512676, in combination with first-line taxane plus platinum chemotherapy for advanced-stage non-small-cell lung cancer.

Authors:  Christian Manegold; Donald Gravenor; Donald Woytowitz; Jörg Mezger; Vera Hirsh; Gary Albert; Mohammed Al-Adhami; David Readett; Arthur M Krieg; Cynthia Gail Leichman
Journal:  J Clin Oncol       Date:  2008-08-20       Impact factor: 44.544

Review 9.  Treatment of squamous cell carcinoma of the head and neck in the metastatic and refractory settings: advances in chemotherapy and the emergence of small molecule epidermal growth factor receptor kinase inhibitors.

Authors:  Syed M Ahmed; Ezra E W Cohen
Journal:  Curr Cancer Drug Targets       Date:  2007-11       Impact factor: 3.428

Review 10.  The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications.

Authors:  Michel Zimmermann; Abderrahim Zouhair; David Azria; Mahmut Ozsahin
Journal:  Radiat Oncol       Date:  2006-05-02       Impact factor: 3.481

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  20 in total

1.  The Expression of Toll-like Receptors in Dermatological Diseases and the Therapeutic Effect of Current and Newer Topical Toll-like Receptor Modulators.

Authors:  Whitney Valins; Sadegh Amini; Brian Berman
Journal:  J Clin Aesthet Dermatol       Date:  2010-09

Review 2.  [Immunomodulation as innovative therapy for head and neck tumors : Current developments].

Authors:  P J Schuler; J C Doescher; S Laban; T K Hoffmann
Journal:  HNO       Date:  2016-07       Impact factor: 1.284

Review 3.  The pharmacokinetics of Toll-like receptor agonists and the impact on the immune system.

Authors:  Abbi L Engel; Gregory E Holt; Hailing Lu
Journal:  Expert Rev Clin Pharmacol       Date:  2011-03       Impact factor: 5.045

Review 4.  Immune Modulation of Head and Neck Squamous Cell Carcinoma and the Tumor Microenvironment by Conventional Therapeutics.

Authors:  Sayuri Miyauchi; Sangwoo S Kim; John Pang; Kathryn A Gold; J Silvio Gutkind; Joseph A Califano; Loren K Mell; Ezra E W Cohen; Andrew B Sharabi
Journal:  Clin Cancer Res       Date:  2019-02-27       Impact factor: 12.531

5.  The Optimal Second-Line Systemic Treatment Model for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: A Bayesian Network Meta-Analysis.

Authors:  Ze-Jiang Zhan; Wen-Yu Yao; Fang Zhang; Wen-Ze Qiu; Kai- Liao; Jian-Hui Feng; Jin-Yun Tan; Hui Liu; Tai-Ze Yuan; Rong-Hui Zheng; Ya-Wei Yuan
Journal:  Front Immunol       Date:  2021-08-02       Impact factor: 7.561

Review 6.  Intratumoural immunotherapy: activation of nucleic acid sensing pattern recognition receptors.

Authors:  Sudhir Agrawal; Ekambar R Kandimalla
Journal:  Immunooncol Technol       Date:  2019-10-16

Review 7.  Trial Watch: Immunostimulation with Toll-like receptor agonists in cancer therapy.

Authors:  Kristina Iribarren; Norma Bloy; Aitziber Buqué; Isabelle Cremer; Alexander Eggermont; Wolf Hervé Fridman; Jitka Fucikova; Jérôme Galon; Radek Špíšek; Laurence Zitvogel; Guido Kroemer; Lorenzo Galluzzi
Journal:  Oncoimmunology       Date:  2015-09-02       Impact factor: 8.110

Review 8.  Current Prospects of Molecular Therapeutics in Head and Neck Squamous Cell Carcinoma.

Authors:  K Devaraja
Journal:  Pharmaceut Med       Date:  2019-08

Review 9.  Toll-Like Receptor 9 Agonists for Cancer Therapy.

Authors:  Davide Melisi; Melissa Frizziero; Anna Tamburrino; Marco Zanotto; Carmine Carbone; Geny Piro; Giampaolo Tortora
Journal:  Biomedicines       Date:  2014-08-04

Review 10.  Novel Immunotherapeutic Approaches for Head and Neck Squamous Cell Carcinoma.

Authors:  Darrin V Bann; Daniel G Deschler; Neerav Goyal
Journal:  Cancers (Basel)       Date:  2016-09-22       Impact factor: 6.639

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