ramucirumab

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Ligands
ramucirumab

GtoPdb Ligand ID: 7390

Synonyms: Cyramza® | IMC-1121B

ramucirumab is an approved drug (FDA & EMA (2014))

Comment: Ramucirumab is an anti-VEGF2 receptor (KDR) monoclonal antibody that is used in oncology.

Peptide sequences and structural information for ramucirumab are available from its IMGT/mAb-DB record.

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Summary of Clinical Use
In 2012, the EMA granted orphan drug approval for ramucirumab for the treatment of hepatocellular carcinoma and gastric cancer. The US FDA granted full approval in 2014 firstly as a monotherapy for the treatment of advanced stomach cancer or adenocarcinoma of the gastroesophageal junction, and latterly in combination with paclitaxel for the same patient group. Ramucirumab was approved by the FDA to treat patients with metastatic non-small cell lung cancer (NSCLC) in December 2014. Further approval was granted in April 2015 for the treatment of patients with metastatic colorectal cancer (mCRC) in combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil) chemotherapy and in particular for patients with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (eg capecitabine, floxuridine, or 5-fluorouracil). In May 2019, the FDA expanded approval to include the treatment of hepatocellular carcinoma (HCC) patients who are intolerant of, or who have experienced disease progression on or after treatment with the kinase inhibitor sorafenib, and who have an elevated baseline alpha fetoprotein (≥400 ng/mL). This approval was based on results from clinical trial NCT02435433 which showed that in these patients ramucirumab increased overall survival by 1.2 months compared to placebo [3]. Click here to link to ClinicalTrials.gov's full list of ramucirumab trials. June 2020 saw FDA approval expanded to include use of ramucirumab in combination with the small molecule EGFR inhibitor erlotinib, as first-line treatment for metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations.

Summary of Clinical Use

In 2012, the EMA granted orphan drug approval for ramucirumab for the treatment of hepatocellular carcinoma and gastric cancer. The US FDA granted full approval in 2014 firstly as a monotherapy for the treatment of advanced stomach cancer or adenocarcinoma of the gastroesophageal junction, and latterly in combination with paclitaxel for the same patient group. Ramucirumab was approved by the FDA to treat patients with metastatic non-small cell lung cancer (NSCLC) in December 2014.
Further approval was granted in April 2015 for the treatment of patients with metastatic colorectal cancer (mCRC) in combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil) chemotherapy and in particular for patients with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (eg capecitabine, floxuridine, or 5-fluorouracil).
In May 2019, the FDA expanded approval to include the treatment of hepatocellular carcinoma (HCC) patients who are intolerant of, or who have experienced disease progression on or after treatment with the kinase inhibitor sorafenib, and who have an elevated baseline alpha fetoprotein (≥400 ng/mL). This approval was based on results from clinical trial NCT02435433 which showed that in these patients ramucirumab increased overall survival by 1.2 months compared to placebo [3].
Click here to link to ClinicalTrials.gov's full list of ramucirumab trials.
June 2020 saw FDA approval expanded to include use of ramucirumab in combination with the small molecule EGFR inhibitor erlotinib, as first-line treatment for metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations.

Mechanism Of Action and Pharmacodynamic Effects
KDR (VEGFR2) and the receptor's endogenous ligand, vascular endothelial growth factor (VEGF), are often present in certain types of cancer cells. Ramucirumab works by binding to VEGFR2 and blocking the pro-angiogenic effects of VEGF [1-2]. This reduces a tumour's ability to grow new blood vessels, thereby slowing down tumour growth.

Mechanism Of Action and Pharmacodynamic Effects

KDR (VEGFR2) and the receptor's endogenous ligand, vascular endothelial growth factor (VEGF), are often present in certain types of cancer cells. Ramucirumab works by binding to VEGFR2 and blocking the pro-angiogenic effects of VEGF [1-2]. This reduces a tumour's ability to grow new blood vessels, thereby slowing down tumour growth.

Clinical Trials
Clinical Trial ID	Title	Type	Source	Comment	References
NCT02435433	A Study of Ramucirumab (LY3009806) Versus Placebo in Participants With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein	Phase 3 Interventional	Eli Lilly and Company