Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2015 Jun 15;21(12):2722-9.
doi: 10.1158/1078-0432.CCR-14-2780. Epub 2015 Mar 16.

TBCRC 019: A Phase II Trial of Nanoparticle Albumin-Bound Paclitaxel with or without the Anti-Death Receptor 5 Monoclonal Antibody Tigatuzumab in Patients with Triple-Negative Breast Cancer

Andres Forero-Torres  1 , Katherine E Varley  2 , Vandana G Abramson  3 , Yufeng Li  4 , Christos Vaklavas  4 , Nancy U Lin  5 , Minetta C Liu  6 , Hope S Rugo  7 , Rita Nanda  8 , Anna M Storniolo  9 , Tiffany A Traina  10 , Sujata Patil  10 , Catherine H Van Poznak  11 , Julie R Nangia  12 , William J Irvin Jr  13 , Helen Krontiras  4 , Jennifer F De Los Santos  4 , Paul Haluska  14 , William Grizzle  4 , Richard M Myers  2 , Antonio C Wolff  15 ; Translational Breast Cancer Research Consortium (TBCRC)
Affiliations
Clinical Trial

TBCRC 019: A Phase II Trial of Nanoparticle Albumin-Bound Paclitaxel with or without the Anti-Death Receptor 5 Monoclonal Antibody Tigatuzumab in Patients with Triple-Negative Breast Cancer

Andres Forero-Torres et al. Clin Cancer Res. .

Abstract

Purpose: Tigatuzumab (TIG), an agonistic anti-DR5 antibody, triggers apoptosis in DR5(+) human tumor cells without crosslinking. TIG has strong in vitro/in vivo activity against basal-like breast cancer cells enhanced by chemotherapy agents. This study evaluates activity of TIG and chemotherapy in patients with metastatic triple-negative breast cancer (TNBC).

Experimental design: Randomized 2:1 phase II trial of albumin-bound paclitaxel (nab-PAC) ± TIG in patients with TNBC stratified by prior chemotherapy. Patients received nab-PAC weekly × 3 ± TIG every other week, every 28 days. Primary objective was within-arm objective response rate (ORR). Secondary objectives were safety, progression-free survival (PFS), clinical benefit, and TIG immunogenicity. Metastatic research biopsies were required.

Results: Among 64 patients (60 treated; TIG/nab-PAC n = 39 and nab-PAC n = 21), there were 3 complete remissions (CR), 8 partial remissions (PR; 1 almost CR), 11 stable diseases (SD), and 17 progressive diseases (PD) in the TIG/nab-PAC arm (ORR, 28%), and no CRs, 8 PRs, 4 SDs, and 9 PDs in the nab-PAC arm (ORR, 38%). There was a numerical increase in CRs and several patients had prolonged PFS (1,025+, 781, 672, 460, 334) in the TIG/nab-PAC arm. Grade 3 toxicities were 28% and 29%, respectively, with no grade 4-5. Exploratory analysis suggests an association of ROCK1 gene pathway activation with efficacy in the TIG/nab-PAC arm.

Conclusions: ORR and PFS were similar in both. Preclinical activity of TIG in basal-like breast cancer and prolonged PFS in few patients in the combination arm support further investigation of anti-DR5 agents. ROCK pathway activation merits further evaluation.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: The following authors have the following conflict of interest to disclose: XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX. The remaining authors have no conflict of interest to disclose.

Figures

Figure 1.
Figure 1.
A. Progression Free Survival for each arm of the trial B. Progression Free Survival According to Prior Therapy for all Patients Enrolled in the Trial
Figure 1.
Figure 1.
A. Progression Free Survival for each arm of the trial B. Progression Free Survival According to Prior Therapy for all Patients Enrolled in the Trial
Figure 2.
Figure 2.
Apoptotic membrane blebbing through DR5/Casp-3/ROCK1 signaling pathway. Genes associated with response to treatment with nab-PAC and TIG are highlighted in orange.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Mayer IA, Abramson VG, Lehmann BD, Pietenpol JA: New strategies for triple-negative breast cancer—deciphering the heterogeneity. Clin Cancer Res 2014, 20: 782–790. - PMC - PubMed
    1. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumours. Nature 2000, 406: 747–752. - PubMed
    1. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lonning PE, Borresen-Dale AL: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001, 98: 10869–10874. - PMC - PubMed
    1. Cancer Genome Atlas Network: Comprehensive molecular portraits of human breast tumors. Nature 2012, 490: 61–70. - PMC - PubMed
    1. Montagna E, Maisonneuve P, Rotmensz N, Cancello G, Iorfida M, Balduzzi A, Galimberti V, Veronesi P, Luini A, Pruneri G, Bottiglieri L, Mastropasqua MG, Goldhirsch A, Viale G, Colleoni M: Heterogeneity of triple-negative breast cancer: histologic subtyping to inform the outcome. Clin Breast Cancer 2013, 13: 31–39. - PubMed

Publication types

MeSH terms

Substances