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.
Date
2019-07-15ICR Author
Author
Jones, RL
Chawla, SP
Attia, S
Schöffski, P
Gelderblom, H
Chmielowski, B
Le Cesne, A
Van Tine, BA
Trent, JC
Patel, S
Wagner, AJ
Chugh, R
Heyburn, JW
Weil, SC
Wang, W
Viele, K
Maki, RG
Type
Journal Article
Metadata
Show full item recordAbstract
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/m2 gemcitabine on days 1 and 8 and 75 mg/m2 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.
Collections
Subject
MORAb-004
endosialin
ontuxizumab
sarcomas
tumor endothelial marker 1 (TEM-1)
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
Antigens, CD
Antigens, Neoplasm
Antimetabolites, Antineoplastic
Antineoplastic Combined Chemotherapy Protocols
Biomarkers, Tumor
Cohort Studies
Deoxycytidine
Docetaxel
Double-Blind Method
Female
Humans
Male
Middle Aged
Progression-Free Survival
Sarcoma
Young Adult
Language
eng
Date accepted
2019-02-11
License start date
2019-07-15
Citation
Cancer, 2019, 125 (14), pp. 2445 - 2454
Publisher
WILEY