Clinical Trials Supported by Targos

Trastuzumab Emtansine  (Kadcyla™ )

Trastuzumab Emtansine (T-DM1) for the Treatment of HER2-Positive Cancer with a Focus on Breast Cancer. Rugo HS, et al., Cancer Drug Discovery and Development  (2013): 179-210

 
Trastuzumab Emtansine: First Global Approval. Drugs. 013 Apr 26
 
Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer Hurvitz SA, et al., J Clin Oncol. 2013 31(9): 1157-63

Trastuzumab-DM1: a clinical update of the novel antibody-drug conjugate for HER2-overexpressing breast cancer. Barginear MF, et al., Mol Med. 2012; 18(1): 1473–1479
 
Trastuzumab emtansine for HER2-positive advanced breast cancer. Verma S, et al., N Engl J Med. 2012; 367(19):1783-91
 
Antibody therapy of cancer. Scott AM, et al., Nat Rev Cancer. (2012) 12(4):278-87

The potential for trastuzumab emtansine in human epidermal growth factor receptor 2 positive metastatic breast cancer: latest evidence and ongoing studies Hurvitz, SA and Kakkar R. Therapeutic Advances in Medical Oncology (2012) 4 (5): 235-245 
 
Exploratory Analysis Of The Relationship Between Her2 Expression (By qRT-PCR) And Efficacy With First-Line Trastuzumab Emtansine (T-DM1) vs Trastuzumab Plus Docetaxel (Ht) In a Randomized Phase 2 Study of Patients (Pts) With Her2-Positive mBC. Perez EA et al., Ann Oncol (2012) 23 (9)
 
From ASCO-breast cancer: EMILIA trial offers hope. Hutchinson L.  Nat Rev Clin Oncol. (2012) 9(8):430

A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. Krop IE, et al. (2012). J. Clin. Oncol. 30:3234–41

Phase II Study of the Antibody Drug Conjugate Trastuzumab-DM1 for the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer After Prior HER2-Directed Therapy. Burris, H.A. et al. J Clin Oncol, (2010): 1527-7755
 
A phase Ib/II trial of trastuzumab-DM1 with Pertuzumab for patients with HER2-positive, locally advanced or metastatic breast cancer: interim efficacy and safety results. Dieras V, et al., (2010) Abstract P3-14-01:. Cancer Res. 70 (24 Suppl 2).
 
Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. Krop IE, et al., (2010) J. Clin.Oncol. 28: 2698–704

A phase II study of trastuzumab-DM1 (T-DM1), a HER2 antibody-drug conjugate (ADC), in patients (pts) with HER2+ metastatic breast cancer (MBC): Final results. Vogel, CL et al., J Clin Oncol, (2009) Vol 27(15S): 1017
 
Quantitative assessment of HER2 status and correlation with efficacy for patients (pts) with metastatic breast cancer (MBC) in a phase II study of trastuzumab-DM1 (T-DM1). Krop, IE. et al., J Clin Oncol, (2009) Vol 27(15S): 1003
 
A phase I study of trastuzumab-DM1 (T-DM1), a first-in-class HER2 antibody-drug conjugate (ADC), in patients (pts) with advanced HER2+ breast cancer (BC). M. Beeram et al., J Clin Oncol, (2008) Vol 26 (15S): 1028

 

Trastuzumab (Herceptin®)

Targos served as a central laboratory for the following clinical studies/trials.

Herceptin Adjuvant (HERA) trial. A Randomised Three-Arm Multi-Centre Comparison Of 1 Year And 2 Years Of Herceptin Versus No Herceptin In Women With HER2-Positive Primary Breast Cancer Who Have Completed Adjuvant Chemotherapy. Reference: ClinicalTrials.gov

Trastuzumab for Gastric Cancer (ToGA) trial. A Randomized, Open-label Study of the Effect of First-line Herceptin in Combination With a Fluoropyrimidine and Cisplatin Versus Chemotherapy Alone on Overall Survival in Patients With HER2-positive Advanced Gastric Cancer. Reference: ClinicalTrials.gov

HannaH study. HannaH study is a Phase III, open-label study involving 596 women with HER2 positive early breast cancer. The study was designed to compare trastuzumab concentration in the blood (pharmacokinetics), efficacy and safety of Herceptin SC to that of Herceptin IV. Reference: www.roche.com/media/media_releases/med-cor-2011-10-18.htm

HELOISE study: A Study of Herceptin (Trastuzumab) in Combination With Cisplatin/Capecitabine Chemotherapy in Patients With HER2-Positive Metastatic Gastric or Gastro-Esophageal Junction Cancer. Reference: ClinicalTrials.gov

 

Erlotinib (Tarceva®)

Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Ciuleanu T, et al., Lancet Oncol. (2012) 13(3):300-8

Efficacy and safety of maintenance erlotinib in Asian patients with advanced non-small-cell lung cancer: a subanalysis of the phase III, randomized SATURN study. Wu YL et al., Lung Cancer. (2012) 77(2):339-45

The SATURN trial: the value of maintenance erlotinib in patients with non-small-cell lung cancer. Neal JW. Future Oncol. (2010) 6(12):1827-32

Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Cappuzzo F. et al., Lancet Oncol. (2010) 11(6):521-9

Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Ciuleanu T, et al., Lancet Oncol. (2012) 13(3):300-8

 

Pertuzumab (Perjeta™)

Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Swain SM, et al., Lancet Oncol. 2013 Apr 17.

Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Gianni L, et al., Lancet Oncol. 2012 Jan;13(1):25-32.

 

Vemurafenib (ZELBORAF®)

Improved survival with vemurafenib in melanoma with BRAF V600E mutation. Chapman PB, et al.,  N Engl J Med. 2011 Jun 30;364(26):2507-16.

 

Bevacizumab (Avastin®)

Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. Van Cutsem E et.al., J Clin Oncol. 2012 Jun 10:30(17): 2119-27

Biomarker results from the AVADO phase 3 trial of first-line bevacizumab plus docetaxel for HER2-negative metastatic breast cancer. Miles DW et. al., Br J Cancer. 2013. Mar 19:108(5):1052-60

Representative Publications

Kassel Site

HER2 testing in gastric cancer: a practical approach. Rüschoff J, et al., Mod Pathol. 2012 May;25(5):637-50

Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. Van Cutsem E, et al., J Clin Oncol. 2012 Jun 10;30(17):2119-27.

Quality assessment of HER2 testing by monitoring of positivity rates. Choritz H, et al., and Study Group HER2 Monitor. Virchows Arch. 2011 Sep;459(3):283-9

Improved survival with vemurafenib in melanoma with BRAF V600E mutation. Chapman PB, et al., N Engl J Med. 2011 Jun 30;364(26):2507-16

HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Rüschoff J, et al., Virchows Arch. 2010 Sep;457(3):299-307

Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Cappuzzo F, et al., Lancet Oncol. 2010 Jun;11(6):521-9

Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Gianni L, et al., Lancet. 2010 Jan 30;375(9712):377-84.

Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Bang YJ, et al., Lancet. 2010 Aug 28;376(9742):687-97

EGFR fluorescence in situ hybridisation assay: guidelines for application to non-small-cell lung cancer. Varella-Garcia M, et al., J Clin Pathol. 2009 Nov;62(11):970-7

Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. Kaufman B, et al., J Clin Oncol. 2009 Nov 20;27(33):5529-37

Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. Piccart-Gebhart MJ, et al., N Engl J Med. 2005 Oct 20;353(16):1659-72

Emerging technologies for assessing HER2 amplification. Penault-Llorca F, et al., Am J Clin Pathol. 2009 Oct;132(4):539-48

Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial. Dowsett M, et al., J Clin Oncol. 2009 Jun 20;27(18):2962-9

Value and limitations of measuring HER-2 extracellular domain in the serum of breast cancer patients. Leary AF, et al., J Clin Oncol. 2009 Apr 1;27(10):1694-705

Central HER2 IHC and FISH analysis in a trastuzumab (Herceptin) phase II monotherapy study: assessment of test sensitivity and impact of chromosome 17 polysomy. Hofmann M, et al., J Clin Pathol. 2008 Jan;61(1):89-94

Implementation of External Quality Assurance Trials for Immunohistochemically Determined Breast Cancer Biomarkers in Germany. von Wasielewski R, et al., Breast Care (Basel). 2008;3(2):128-33

Interlaboratory trials for quality assurance of breast cancer biomarkers in Germany. Krusche CA, et al., Pathologe. 2008 Jul;29(4):315-20

Proficiency testing of immunohistochemical biomarker assays in breast cancer. Wasielewski RV, et al., Virchows Arch. 2008 Dec;453(6):537-43

Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Hofmann M, et al., Histopathology. 2008 Jun;52(7):797-805

What causes discrepancies in HER2 testing for breast cancer? A Japanese ring study in conjunction with the global standard. Umemura S, et al., Am J Clin Pathol. 2008 Dec;130(6):883-91

Chromogenic in situ hybridisation for the assessment of HER2 status in breast cancer: an international validation ring study. van de Vijver MJ et al., Breast Cancer Res. 2007;9(5):R68

Standardization of HER2 testing: results of an international proficiency-testing ring study. Dowsett M, et al., Mod Pathol. 2007 May;20(5):584-91

Cologne Site

Lessons Learned From Lung Cancer Genomics: The Emerging Concept of Individualized Diagnostics and Treatment. Büttner et.al., J Clin Oncol. 2013: 31 (15) 1858-1865

Impairment of prostate cancer cell growth by a selective and reversible lysine-specific demethylase 1 inhibitor. Willmann D, et al., Int J Cancer. 2012 Dec 1;131(11):2704-9.

Hepatocarcinogenesis in non-cirrhotic liver is associated with a reduced number of clonal hepatocellular patches in non-tumorous liver parenchyma. Adam AC, et al., J Pathol. 2012 Nov;228(3):333-40.

Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Peifer M, et al., Nat Genet. 2012 Oct;44(10):1104-10

A dual role of linker histone H1.4 Lys 34 acetylation in transcriptional activation. Kamieniarz K, et al., Genes Dev. 2012 Apr 15;26(8):797-802

Targeted Expression of Mutated ALK Induces Neuroblastoma in Transgenic Mice. Heukamp LC, et al., Sci Transl Med 4 July 2012: Vol. 4, Issue 141, p. 141ra91

Definition of a fluorescence in situ hybridization score identifies high- and low-level FGFR1 amplification types in squamous cell lung cancer. Schildhaus HU, et al., Mod Pathol. 25:1473-80, 2012

Activating PDGFRA mutations in inflammatory fibroid polyps occur in exons 12, 14 and 18 and are associated with tumour localization. Huss S, et al., Histopathology. 61:59-68, 2012

FHL2 expression in peritumoural fibroblasts correlates with lymphatic metastasis in sporadic but not in HNPCC-associated colon cancer. Gullotti L et al., Lab Invest. 2011 Dec;91(12):1695-705

High nuclear poly(adenosine diphosphate-ribose) polymerase expression is predictive for BRCA1- and BRCA2-deficient breast cancer. Ozretić L, et al., J Clin Oncol. 2011 Dec 1;29(34):4586-8

Lysine-specific demethylase 1 (LSD1) is highly expressed in solitary fibrous tumors, synovial sarcomas, rhabdomyosarcomas, desmoplastic small round cell tumors and malignant peripheral nerve sheath tumors. Schildhaus HU, et al., Hum Pathol. 42:1667-75, 2011

Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Weiss J, et al., Sci Transl Med. 2010 Dec 15;2(62):62ra93

Phosphorylation of histone H3T6 by PKCbeta(I) controls demethylation at histone H3K4. Metzger E, et al., Nature. 2010 Apr 1;464(7289):792-6

Inflammatory fibroid polyps harbour mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene. Schildhaus HU, et al., J Pathol. 216:176-82, 2008

Therapeutic consequences from molecular biology for gastrointestinal stromal tumor patients affected by neurofibromatosis type 1. Mussi C, et al., Clin Cancer Res. 14:4550-5, 2008