Merck and Eisai Submit New Indication Application in Japan for Lenvima (Lenvatinib) in Unresectable Thymic Carcinoma with a Disease Control Rate of 95.2%

August 03, 2020 News /BioonBIOON/ -- Eisai and MSD K.K., the Japanese subsidiary of Merck & Co., Inc., recently announced the joint submission in Japan of a new indication application for the anticancer drug Lenvima (Lenvima®, generic name: lenvatinib), a multi-receptor tyrosine kinase inhibitor, for the treatment of unresectable thymic cancer. In June 2020, Lenvima was granted orphan drug designation in Japan for the treatment of unresectable thymic cancer.

Thymic carcinoma is an extremely rare disease with a low incidence rate. It is estimated that there are only 140–200 patients in Japan. For unresectable thymic carcinoma, platinum-based chemotherapy is recommended as the first-line treatment. However, since standard therapies for second-line or subsequent treatments have not yet been established, the disease remains associated with a poor prognosis, highlighting the need for the development of new therapeutic agents.

This application is based on the results of an open-label, single-arm, multicenter, investigator-initiated Phase II clinical study (NCCH1508, REMORA) conducted in Japan. The study evaluated the efficacy and safety of Lenvima as monotherapy in 42 patients with thymic carcinoma who had experienced disease progression after at least one prior platinum-based regimen. In the study, Lenvima was initiated at a dose of 24 mg once daily, with dose reductions permitted as appropriate based on patient condition, and treatment continued until disease progression or unacceptable toxicity occurred. The primary endpoint was the objective response rate (ORR) determined by independent radiological review using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

The results showed that the objective response rate (ORR) for Lenvima monotherapy was 38.1% (90% CI: 25.6–52.0). The study met its primary endpoint, as the lower bound of the confidence interval exceeded the prespecified statistical criterion (threshold ORR of 10%). All objective responses were partial responses (PR); 57.1% of patients achieved stable disease, and 4.8% experienced disease progression, resulting in a disease control rate (DCR) of 95.2% (95% CI: 83.8–99.4). The median progression-free survival (PFS) was 9.3 months (95% CI: 7.7–13.9), and the median overall survival (OS) was not reached (95% CI: 16.1–NR).

In the study, the three most common treatment-related adverse events wereHypertension(88.1%), proteinuria (71.4%), and palmar-plantar erythrodysesthesia syndrome (69.0%), which is consistent with the safety profile observed in previously approved indications. Other common adverse events included: hypothyroidism (64.3%), diarrhea (57.1%), thrombocytopenia (54.8%), decreased appetite (42.9%), weight loss (40.5%), dysphonia (40.5%), elevated aspartate aminotransferase (33.3%), asthenia (33.3%), and stomatitis (33.3%).

Lenvima is a kinase inhibitor discovered and developed by Eisai. This drug is an oral multi-receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activity of vascular endothelial growth factor receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). In addition to inhibiting normal cell functions, Lenvima also inhibits other kinases associated with pathological angiogenesis, tumor growth, and cancer progression, including fibroblast growth factor (FGF) receptors FGFR1-4, platelet-derived growth factor receptor alpha (PDGFRα), KIT, and RET. Lenvima can reduceTumorRelevant macrophages, increasing activated cytotoxic T cells.

As of now, the approved indications for Lenvima include: thyroid cancer, hepatocellular carcinoma (HCC), in combination with everolimus for the treatment of renal cell carcinoma (second-line therapy), and in combination with Keytruda (pembrolizumab, PD-1Tumorimmunotherapy) for the treatment of advanced endometrial cancer. In Europe, lenvatinib is marketed under the brand name Kisplyx for the treatment of renal cell carcinoma.

Eisai and MSD entered into a strategic collaboration in March 2018 to develop and commercialize Lenvima globally. In March and August 2018, Lenvima received approval in Japan, the United States, and the European Union, respectively, becoming the first new first-line therapy approved in these markets in the past decade for advanced or unresectable hepatocellular carcinoma (HCC).

In China, Lenvima (Lenvatinib) was approved in September 2018 as a monotherapy for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC) who had not previously received systemic therapy. China is the world'sLiver CancerThe country with the largest patient population. In November 2018, Lenvima was launched in China, marking the first new systemic therapy for the first-line treatment of unresectable hepatocellular carcinoma (HCC) in China in nearly a decade.

In December 2019, a new indication for Lenvima in the treatment of differentiated thyroid cancer (DTC) was approved, marking the second indication for the drug approved in China. (Bioon.com)

Original Source:appLICATION FOR ADDITIONAL INDICATION OF ANTI CANCER AGENT LENVIMA® FOR UNRESECTABLE THYMIC CARCINOMA SUBMITTED IN JAPAN