@article{873da97969504b0a9b39304f774b70eb,
title = "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",
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/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.",
keywords = "MORAb-004, endosialin, ontuxizumab, sarcomas, tumor endothelial marker 1 (TEM-1)",
author = "Jones, {Robin L.} and Chawla, {Sant P.} and Steven Attia and Patrick Sch{\"o}ffski and Hans Gelderblom and Bartosz Chmielowski and {Le Cesne}, Axel and {Van Tine}, {Brian A.} and Trent, {Jonathan C.} and Shreyaskumar Patel and Wagner, {Andrew J.} and Rashmi Chugh and Heyburn, {John W.} and Weil, {Susan C.} and Wenquan Wang and Kert Viele and Maki, {Robert G.}",
note = "Funding Information: This trial was supported by Morphotek, Inc (Exton, Pennsylvania). The University of Texas MD Anderson Cancer Center is supported by the National Institutes of Health (grant P30 CA016672). Funding Information: Robin L. Jones reports personal fees from Adaptimmune, Blueprint, Clinigen, Eisai, Epizyme, Daiichi, Deciphera, Immune Design, Lilly, Merck, and PharmaMar outside the submitted work. Sant P. Chawla reports grants from Amgen, Roche, Threshold Pharmaceuticals, GlaxoSmithKline, CytRx, Ignyta, Immune Design, TRACON Pharmaceuticals, SARC, Karyopharm Therapeutics, and Jansen outside the submitted work. Steven Attia reports grants from Bayer, AB Science, TRACON Pharmaceuticals, CytRx, Novartis, Daiichi Sankyo, Lilly, Immune Design, Karyopharm Pharmaceuticals, Epizyme, Blueprint Medicines, Genmab, CBA Pharmaceuticals, the Desmoid Tumor Research Foundation, Merck, Deciphera, Takeda Oncology, Philogen, Gradilis, Incyte, Threshold Pharmaceuticals, Bayer, BTG, Bavarian Nordic, Advenchen Laboratories, SpringWorks, and Adaptimmune as well as travel expenses from TRACON Pharmaceuticals and Immune Design outside the submitted work. Patrick Sch{\"o}ffski reports institutional support from Plexxikon, Eisai, Loxo, Lilly, Blueprint Medicines, Ellipses Pharma, Deciphera, Merck, Servier, Genmab, Adaptimmune, Intellisphere, Transgene, Boehringer Ingelheim, CoBioRes NV, Exelixis, G1 Therapeutics, Novartis, and PharmaMar outside the submitted work. Bartosz Chmielowski reports personal fees from Bristol-Myers Squibb, Merck, Genentech/Roche, Iovance, HUYA, Compugen, Array BioPharma, Regeneron, Biothera, Janssen, and Novartis outside the submitted work. Axel Le Cesne reports personal fees from PharmaMar, Pfizer, and Lilly outside the submitted work. Brian A. Van Tine reports personal fees from Epizyme, Lilly, CytRx, Janssen, Caris, Immune Design, Daiichi Sankyo, Adaptimmune, and Plexxikon and grants from Pfizer, Merck, TRACON Pharmaceuticals, and Morphotek outside the submitted work. Shreyaskumar Patel reports grants and personal fees from Janssen and personal fees from PharmaMar and MJ Hennessey/OncLive during the conduct of the study; he also reports grants from Blueprint Medicines and personal fees from Novartis Oncology, Immune Design, Epizyme, Eli Lilly, CytRx, and EMD Serono outside the submitted work. Andrew J. Wagner reports personal fees from Novartis and NanoCarrier; grants and personal fees from Daiichi-Sankyo and Eli Lilly; and grants from Karyopharm, Aadi Bioscience, Plexxikon, and Celldex outside the submitted work. Rashmi Chugh reports grants and nonfinancial support from Morphotek during the conduct of the study. She also reports grants, personal fees, and nonfinancial support from Epizyme; personal fees from EMD Serono, Janssen, and Immune Design; and grants and nonfinancial support from AADi, Novartis, Lilly, Medivation, MabVax, Advenchen, Pfizer, and Plexxikon outside the submitted work. Kert Viele reports being an employee of Berry Consultants with multiple consulting clients. Robert G. Maki reports personal fees from Arcus, Bayer, Foundation Medicine, the American Association for Cancer Research, the American Society of Clinical Oncology, Springer, UpToDate, and Wiley; grants and personal fees from Janssen, PharmaMar, Presage Biosciences, and TRACON Pharmaceuticals; grants from Daiichi-Sankyo, Genentech, Immune Design, Immunocor, Lilly/ImClone, Regeneron, the Sarcoma Alliance for Research Through Collaboration, and Fondazione Enrico Pallazzo; and other from AADi, Deciphera, Karyopharm, and the American Board of Internal Medicine outside the submitted work. John W. Heyburn, Susan C. Weil, and Wenquan Wang were employed by Morphotek, Inc, during the study. The other authors made no disclosures. Publisher Copyright: {\textcopyright} 2019 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.",
year = "2019",
month = jul,
day = "15",
doi = "10.1002/cncr.32084",
language = "English",
volume = "125",
pages = "2445--2454",
journal = "Cancer",
issn = "0008-543X",
number = "14",
}