Type of information: Granting of the Breakthrough Therapy status
Product name: Lenvima® and Keytruda®
Compound: lenvatinib mesylate and pembrolizumab
Therapeutic area: Cancer - Oncology
- tyrosine kinase inhibitor/monoclonal antibody/immune checkpoint inhibitor. Lenvima®, discovered and developed by Eisai, is an oral molecular targeted agent that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1 (FLT1), VEGFR2 (KDR) and VEGFR3 (FLT4)), and fibroblast growth factor (FGF) receptors FGFR1, 2, 3 and 4 in addition to other proangiogenic and oncogenic pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFR?; KIT; and RET) involved in tumor proliferation. In particular, Lenvima® possesses a new binding mode (Type V) to VEGFR2, as confirmed through X-ray crystal structural analysis, and exhibits rapid and potent inhibition of kinase activity, according to kinetic analysis.
- Keytruda® (pembrolizumab) is a humanized monoclonal antibody that blocks the interaction between PD-1 (programmed death receptor-1) and its ligands, PD-L1 and PD-L2.
Company: Eisai (Japan) Merck&Co (USA - NJ)
Disease: renal cell carcinoma
- • On January 9, 2018, Eisai and Merck&Co announced that they received Breakthrough Therapy Designation from the FDA for Eisai's multiple receptor tyrosine kinase inhibitor Lenvima® (lenvatinib) in combination with Merck's anti-PD-1 therapy Keytruda® (pembrolizumab) for the potential treatment of patients with advanced and/or metastatic renal cell carcinoma (RCC). The combination therapy is being jointly developed by Eisai and Merck&Co. This is the second Breakthrough Therapy Designation for Lenvima® and the twelfth Breakthrough Therapy Designation granted to Keytruda®.
- This designation was based on the results of the RCC cohort in Study 111, a multicenter, open-label phase 1b/2 clinical study being carried out in the U.S. and the European Union (EU) to evaluate the efficacy and safety of Lenvima® in combination with Keytruda® in subjects with selected solid tumors. The primary objective of the phase 1b part was to determine the maximum tolerated dose. Patients with unresectable solid tumors (renal cell carcinoma, endometrial cancer, non-small cell lung cancer, urothelial cancer, squamous cell head and neck cancer and melanoma) who had progressed after treatment with approved therapies or for which there are no standard effective therapies available were administered 24 mg of Lenvima® orally daily, as well as 200 mg of Keytruda® intravenously every three weeks. Dose reductions of Lenvima® were permitted based on observed toxicity. The phase 2 part was conducted with patients who had select solid tumors with 0-2 prior lines of systemic therapy (unless discussed with the sponsor), with a recommended dosage of 20 mg of Lenvima® daily and 200 mg of Keytruda® every three weeks as determined based on the results of the phase 1b part. The primary endpoint of the phase 2 part was objective response rate at 24 weeks after treatment began, with select secondary endpoints including objective response rate, disease control rate, progression-free survival and duration of response. Currently, the phase 2 part is underway, with enrollment expanded for the endometrial cancer cohort.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: