|Elimination half-life||14 days|
|Chemical and physical data|
|Molar mass||143.6 kg/mol g·mol−1|
|(what is this?)|
Ramucirumab (LY3009806, IMC-1121B, trade name Cyramza) is a fully human monoclonal antibody (IgG1) developed for the treatment of solid tumors. This drug was developed by ImClone Systems Inc. It was isolated from a native phage display library from Dyax.
On 21 April 2014, the US Food and Drug Administration (FDA) approved ramucirumab as a single-agent treatment for advanced gastric cancer or gastro-esophageal junction (GEJ) adenocarcinoma after prior treatment with fluoropyrimidine- or platinum-containing chemotherapy. The approval was based on the results of the REGARD trial, a phase III, international, randomized, double-blind, placebo-controlled study, that evaluated the safety and efficacy of ramucirumab combinated with best supportive care versus placebo.
Ramucirumab has also been studied in combination with paclitaxel (a type of chemotherapy) and received additional FDA approval on 5 November 2014 as a treatment for people with advanced gastric cancer or GEJ adenocarcinoma after prior treatment with fluoropyrimidine- or platinum-based chemotherapy. The approval was based on the results of the RAINBOW trial, that compared ramucirumab plus paclitaxel or paclitaxel alone.
On 12 December 2014, the FDA approved ramucirumab in combination with docetaxel for treatment of metastatic non-small-cell lung carcinoma (NSCLC) with disease progression during or after first-line platinum-containing chemotherapy. The approval was based on REVEL trial.
On 24 April 2015, ramucirumab was approved by FDA for the treatment of pacient with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and fluoropyrimidine. The approval was based on the results of the RAISE trial, a phase III study, which compared ramucirumab plus irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) to FOLFIRI alone.
The most common adverse effects in a study investigating ramucirumab monotherapy were diarrhoea (14% of patients, as compared to 9% under placebo), hyponatraemia (low blood sodium levels; 6% versus 2%), headache (9% versus 3%), and high blood pressure (16% versus 8%).
Mechanism of action
Ramucirumab is a direct VEGFR2 antagonist, that binds with high affinity to the extracellular domain of VEGFR2 and block the binding of natural VEGFR ligands (VEGF-A, VEGF-C and VEGF-D). These ligands are secreted by solid tumors to promote angiogenesis (formation of new blood vessels from pre-existing ones) and enhance tumor blood supply. Binding of ramucirumab to VEGFR2 leads to inhibition of VEGF-mediated tumor angiogenesis.
On September 26, 2013 the manufacturer Eli Lilly announced that its Phase III study for ramucirumab failed to hit its primary endpoint on progression-free survival among women with metastatic breast cancer.
In Feb 2016 it was reported that a phase II trial of adding ramucirumab to docetaxel improved progression-free survival (PFS) compared with docetaxel alone in locally advanced or metastatic urothelial carcinoma. It is now in the RANGE phase III trial for this indication.
- Statement On A Nonproprietary Name Adopted By The USAN Council - Ramucirumab, American Medical Association.
- FierceBiotech: FDA OKs Lilly's blockbuster hopeful ramucirumab for stomach cancer
- Cyramza official website
- Fuchs, Charles S; Tomasek, Jiri; Yong, Cho Jae; Dumitru, Filip; Passalacqua, Rodolfo; Goswami, Chanchal; Safran, Howard; dos Santos, Lucas Vieira; Aprile, Giuseppe (January 2014). "Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial". The Lancet. 383 (9911): 31–39. doi:10.1016/s0140-6736(13)61719-5. ISSN 0140-6736.
- Ohtsu, Atsushi; Schwartz, Jonathan D.; Chandrawansa, Kumari; Ferry, David; Carlesi, Roberto; Emig, Michael; Ajani, Jaffer; Komatsu, Yoshito; Rougier, Philippe (2014-10-01). "Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial". The Lancet Oncology. 15 (11): 1224–1235. doi:10.1016/S1470-2045(14)70420-6. ISSN 1470-2045. PMID 25240821.
- Pérol, Maurice; Yurasov, Sergey; Sashegyi, Andreas; Alexandris, Ekaterine; Cappuzzo, Federico; Reck, Martin; Karaseva, Nina; Grigorescu, Alexandru; Kim, Joo-Hang (2014-08-23). "Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial". The Lancet. 384 (9944): 665–673. doi:10.1016/S0140-6736(14)60845-X. ISSN 0140-6736. PMID 24933332.
- ascopubs.org. doi:10.1200/jco.2015.33.3_suppl.512 https://ascopubs.org/action/captchaChallenge?redirectUrl=http%3A%2F%2Fascopubs.org%2Fdoi%2F10.1200%2Fjco.2015.33.3_suppl.512&. Retrieved 2019-02-09. Missing or empty
- "Cyramza: EPAR – Product Information" (PDF). European Medicines Agency. 21 January 2015.
- Haberfeld, H, ed. (2017). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Cyramza 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung.
- FDA Professional Drug Information on Cyramza.
- Ramucirumab (Cyramza) package insert
- Clinical trial number NCT00703326 for "Phase III Study of Docetaxel + Ramucirumab or Placebo in Breast Cancer" at ClinicalTrials.gov
- Fierce Biotech. "In another stinging setback, Eli Lilly's ramucirumab fails PhIII breast cancer study". Retrieved 27 September 2013.
- Ramucirumab Added to Docetaxel Extends PFS in Urothelial Carcinoma.Feb 2016
- A Study of Ramucirumab (LY3009806) Plus Docetaxel in Participants With Urothelial Cancer (RANGE)