A phase 1 and randomized controlled phase 2 trial of the safety and efficacy of the combination of gemcitabine and docetaxel with ontuxizumab (MORAb-004) in metastatic soft-tissue sarcomas

Jones, R. L., Chawla, S. P., Attia, S., Schoffski, P., Gelderblom, H., Chmielowski, B., Le Cesne, A., Van Tine, B. A., Trent, J. C., Patel, S., Wagner, A. J., Chugh, R., Heyburn, J. W., Weil, S. C., Wang, W., Viele, K., Maki, R. G. (April 2019) A phase 1 and randomized controlled phase 2 trial of the safety and efficacy of the combination of gemcitabine and docetaxel with ontuxizumab (MORAb-004) in metastatic soft-tissue sarcomas. Cancer, 125 (14). pp. 2445-2454. ISSN 0008-543x

URL: https://www.ncbi.nlm.nih.gov/pubmed/31034598
DOI: 10.1002/cncr.32084

Abstract

BACKGROUND: Ontuxizumab, a humanized monoclonal antibody, targets endosialin (tumor endothelial marker 1 [TEM-1] or CD248), which is expressed on sarcoma cells and is believed to be involved in tumor angiogenesis. This is the first trial to evaluate ontuxizumab in patients with sarcoma. METHODS: Part 1 was an open-label, dose-finding, safety lead-in: 4, 6, or 8 mg/kg with gemcitabine and docetaxel (G/D; 900 mg/m(2) gemcitabine on days 1 and 8 and 75 mg/m(2) docetaxel on day 8). In part 2, patients were randomized in a double-blind fashion in 2:1 ratio to ontuxizumab (8 mg/kg) or a placebo with G/D. Randomization was stratified by 4 histological cohorts. RESULTS: In part 2 with 209 patients, no significant difference in progression-free survival between ontuxizumab plus G/D (4.3 months; 95% confidence interval [CI], 2.7-6.3 months) and the placebo plus G/D (5.6 months; 95% CI, 2.6-8.3 months) was observed (P = .67; hazard ratio [HR], 1.07; 95% CI, 0.77-1.49). Similarly, there was no significant difference in median overall survival between the 2 groups: 18.3 months for the ontuxizumab plus G/D group (95% CI, 16.2-21.1 months) and 21.1 months for the placebo plus G/D group (95% CI, 14.2 months to not reached; P = .32; HR, 1.23; 95% CI, 0.82-1.82). No significant differences between the treatment groups occurred for any efficacy parameter by sarcoma cohort. The combination of ontuxizumab plus G/D was generally well tolerated. CONCLUSIONS: Ontuxizumab plus G/D showed no enhanced activity over chemotherapy alone in soft-tissue sarcomas, whereas the safety profile of the combination was consistent with G/D alone.

Item Type: Paper
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > monoclonal antibody
diseases & disorders > cancer > cancer types > sarcoma
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matthew Dunn
Date: 29 April 2019
Date Deposited: 22 May 2019 14:31
Last Modified: 12 Aug 2019 18:18
Related URLs:
URI: http://repository.cshl.edu/id/eprint/37842

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