Cited by 206Monoclonal and Polyclonal Antibodies ResearchToxin Mechanisms and ImmunotoxinsImmunotherapy and Immune Responses

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Cantuzumab Mertansine, a Maytansinoid Immunoconjugate Directed to the CanAg Antigen: A Phase I, Pharmacokinetic, and Biologic Correlative Study

Tolcher, Anthony W., Ochoa, Leonel, Hammond, Lisa A., Patnaik, Amita, Edwards, Tam, Takimoto, Chris, Smith, Lon, de Bono, Johann, Schwartz, Garry, Mays, Theresa, Jonak, Zdenka L., Johnson, Randall, DeWitte, Mark, Martino, Helen, Audette, Charlene, Maes, Kate, Chari, Ravi V.J., Lambert, John M., Rowinsky, Eric K.·2003·Journal of Clinical Oncology

DOI 10.1200/jco.2003.05.137

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Abstract

Purpose: To determine the maximum tolerated dose and pharmacokinetics of cantuzumab mertansine, an immunoconjugate of the potent maytansine derivative (DM1) and the humanized monoclonal antibody (huC242) directed to CanAg, intravenously (IV) once every 3 weeks and to seek evidence of antitumor activity. Patients and Methods: Patients with CanAg-expressing solid malignancies were treated with escalating doses of cantuzumab mertansine administered IV every 3 weeks. The pharmacokinetic parameters of cantuzumab mertansine, the presence of plasma-shed CanAg, and the development of both human antihuman and human anti-DM1 conjugate antibodies also were characterized. Results: Thirty-seven patients received 110 courses of cantuzumab mertansine at doses ranging from 22 to 295 mg/m 2. Acute, transient, and reversible elevations of hepatic transaminases were the principal toxic effects. Nausea, vomiting, fatigue, and diarrhea were common but rarely severe at the highest dose levels. Dose, peak concentration, and area under the concentration–time curve correlated with the severity of transaminase elevation. The mean (± SD) clearance and terminal elimination half-life values for cantuzumab mertansine averaged 39.5 (±13.1) mL/h/m 2 and 41.1 (±16.1) hours, respectively. Strong expression (3+) of CanAg was documented in 68% of patients. Two patients with chemotherapy-refractory colorectal carcinoma had minor regressions, and four patients had persistently stable disease for more than six courses. Conclusion: The recommended dose for cantuzumab mertansine is 235 mg/m 2 IV every 3 weeks. The absence of severe hematologic toxic effects, preliminary evidence of cantuzumab mertansine tumor localization, and encouraging biologic activity in chemotherapy-refractory patients warrant further broad clinical development of this immunoconjugate in CanAg-expressing tumors.

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BackgroundInfluential
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BackgroundMethodResultInfluentialSelf-citation
Update on Emerging Therapies for Advanced Colorectal Cancer
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An antibody–cytotoxic conjugate, BIIB015, is a new targeted therapy for Cripto positive tumours
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Method
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Method
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BackgroundInfluential
Photoactivatable prodrug for simultaneous release of mertansine and CO along with a BODIPY derivative as a luminescent marker in mitochondria: a proof of concept for NIR image-guided cancer therapy
Tiwari, R., Shinde, P. S., Sreedharan, S., Dey, A. K., Vallis, K. A., Mhaske, S. B., Pramanik, S. K., & Das, A. (2020) · Chemical Science · doi:10.1039/d0sc06270g · Cited by 40
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Authors: Tolcher, A. W., Ochoa, L., Hammond, L. A., Patnaik, A., Edwards, T., Takimoto, C., Smith, L., de Bono, J., Schwartz, G., Mays, T., Jonak, Z. L., Johnson, R., DeWitte, M., Martino, H., Audette, C., Maes, K., Chari, R. V. J., Lambert, J. M., & Rowinsky, E. K.
Affiliations: Brooke Army Medical Center (US)
From the Institute for Drug Development, Cancer Therapy and Research Center and The University of Texas Health Science Center at San Antonio; and Brooke Army Medical Center, San Antonio, TX; GlaxoSmithKline, Collegeville, PA; and ImmunoGen Inc., Cambridge, MA.
ORCID: Tolcher, Anthony W.
Patnaik, Amita
Johnson, Randall
Audette, Charlene
Chari, Ravi V.J.
Lambert, John M.
Rowinsky, Eric K.
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2003-01-15
Volume: 21
Issue: 2
Pages: 211-222
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2003.05.137
OpenAlex: W2121080375
Cited by: 206
References: 16
Citations by year: 2026: 1 · 2025: 7 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 8 · 2017: 5 · 2016: 8 · 2015: 19 · 2014: 9 · 2013: 10 · 2012: 16
FWCI: 10.49
Type: journal article
Language: en
Open access: closed
Locations: Journal of Clinical Oncology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: DM1, pharmacokinetics, maximum tolerated dose, hepatotoxicity, colorectal cancer, solid tumors, tumor localization, anticancer activity
MeSH terms: Adult, Aged, Antibodies, Monoclonal, Antineoplastic Agents, Phytogenic, Dose-Response Relationship, Drug, Female, Half-Life, Humans, Infusions, Intravenous, Male, Maytansine, Middle Aged, Neoplasms, Mucin-1, Immunoconjugates, Maximum Tolerated Dose

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Cantuzumab Mertansine, a Maytansinoid Immunoconjugate Directed to the CanAg Antigen: A Phase I, Pharmacokinetic, and Biologic Correlative Study

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