Nimotuzumab is a humanized monoclonal antibody targeting the Epidermal Growth Factor Receptor (EGFR). Nimotuzumab can be used as a monotherapy and in combination with radiation therapy and chemotherapy for the treatment of malignant diseases.
Knowledge of the EGFR function in the malignant process has advanced enormously during the past decade. Its overexpression has been better characterized in different tumor types, but also linked to a worse prognosis in patient as well as radiotherapy and chemotherapy resistance. Additionally, the EGFR signaling pathway is known to contribute to tumor proliferation, apoptosis resistance, angiogenesis, invasion and metastasis. Experiments have shown that nimotuzumab requires bivalent binding (attachment with both antibody arms to two EGF receptors) for efficient accumulation on the cellular surface. The ability to form bivalent bonds is a function of EGFR density on the cellular surface. The selective accumulation of nimotuzumab on cancer cells over-expressing the EGFR is therefore a mechanistic explanation for the very low incidence of side-effects typical in this class of medications, like skin-rash, when adult and pediatric patients are treated with nimotuzumab.
Nimotuzumab was invented at the Center of Molecular Immunology (CIM) in Havana, Cuba and co-developed by YM Biosciences in Canada. Today Nimotuzumab is approved in 30 countries including Asia, South America and Africa for the treatment of squamous cell carcinomas of the head and neck, esophageal cancer, refractory pediatric and adult glioma, nasopharyngeal carcinoma and pancreatic cancer. Nimotuzumab has orphan drug status in the EU and US for pediatric glioma (Diffuse Intrinsic Pontine Glioma) and pancreatic cancer.
A total of 35 clinical trials have been completed with nimotuzumab on several cancer indications:
– Eight trials in squamous cell carcinoma of the head and neck (Canada, Cuba, and India)
– Eight trials in Glioma (Cuba, Germany, Canada and India)
– Five trials in non-small cell lung cancer (Canada, Cuba, India and Japan)
– Three trials in esophageal cancer (Cuba, Brazil and China)
– Two trials in solid tumors (Canada and Japan)
– Two trials in pancreatic cancer (Germany)
– One trial in colorectal cancer (Canada)
– One trial in breast cancer (Cuba)
– One trial in tumors of epithelial origin (Cuba)
– One trial in prostate cancer (Cuba)
– One trial in hepatic cancer (Cuba)
– One trial in gastric cancer (Japan and South Korea)
– One trial in nasopharyngeal cancer (China)
The clinical development program includes an additional 27 clinical trials currently ongoing to investigate the safety and efficacy of nimotuzumab in 11 different localizations such as breast, cervical, colorectal, esophageal, gastric cancer, adult and pediatric glioma, head and neck, nasopharyngeal, non-small cell lung, prostate cancers and other solid tumors.
To date (2015) over 2705 patients have been enrolled in the completed clinical trials, 1939 of them were treated with nimotuzumab and 766 were included on the control group and nearly 4580 more are planned for inclusion in the ongoing studies, from them 2601 have been already included.
Oncoscience GmbH accomplishes the clinical development and preparation for marketing authorization for Nimotuzumab in Europe.
Nimotuzumab is sometimes also referred to as OSAG101, the planned tradename for Nimotuzumab in Europe is TheraCIM®.
The knowledge about nimotuzumab is emerging constantly. New information from preclinical studies as well as data from clinical trials are collected. To date more than 170 articles on the topic have been published of which more than 30 deal with results of clinical trials. Below you can find a selection on various topics related to nimotuzumab:
- reviews / early clinical data
- Giselle Saurez-Martinez et al.: Nimotuzumab, effective immunotherapy for the treatment of malignant epithelial tumors.
- Rojo et al.: Pharmacodynamic trial of nimotuzumab in unresectable squamous cell carcinoma of the head and neck: a SENDO Foundation study.
- You et al.: A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies.
- Okamoto et al.: A phase I, pharmacokinetic and pharmacodynamic study of nimotuzumab in Japanese patients with advanced solid tumors.
- brain tumors
- Bode et al.: Nimotuzumab treatment of malignant gliomas.
- Solomón et al.: Radiotherapy plus nimotuzumab or placebo in the treatment of high grade glioma patients: results from a randomized, double blind trial.
- Solomón et al.: Nimotuzumab in combination with radiotherapy in high grade glioma patients: a single institution experience.
- Massimino et al.: Results of nimotuzumab and vinorelbine, radiation and re-irradiation for diffuse pontine glioma in childhood.
- Bartels et al.: Phase 2 study of safety and efficacy of nimotuzumab in pediatric patients with progressive diffuse intrinsic pontine glioma.
- Westphal et al.: A randomised, open label phase III trial with nimotuzumab, an anti-epidermal growth factor receptor monoclonal antibody in the treatment of newly diagnosed adult glioblastoma.
- Cabanas et al.: Prolonged Use of Nimotuzumab in Children with Central Nervous System Tumors: Safety and Feasibility
- Cabanas et al.: Treatment of children with high grade glioma with nimotuzumab: a 5-year institutional experience
- pancreatic cancer
- B. Schultheis et al.: Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer: a multicenter, randomized phase IIb study. https://academic.oup.com/annonc/article-abstract/28/10/2429/3926574?redirectedFrom=fulltext
- Strumberg et al.: Phase II study of nimotuzumab, a humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, in patients with locally advanced or metastatic pancreatic cancer.
- Su et al.: Efficacy of nimotuzumab plus gemcitabine usage as first-line treatment in patients with advanced pancreatic cancer.
- Arslan et al.: Current and future systemic treatment options in metastatic pancreatic cancer.