Positive Opinion Granted for Advanced Renal Cell Carcinoma Based on Significant Progression-Free Survival (PFS), Overall Survival (OS) and Objective Response Rate (ORR) Benefit Compared to Sunitinib in CLEAR/KEYNOTE-581 Trial

Positive Opinion Granted for Advanced Endometrial Carcinoma Based on Significant OS and PFS Benefit Compared to Chemotherapy in Study 309/KEYNOTE-775 Trial

 

TOKYO and KENILWORTH, N.J., Oct. 18, 2021 ¨C Eisai (Headquarters: Tokyo, CEO: Haruo Naito) and Merck & Co., Inc., Kenilworth, N.J., U.S.A. (known as MSD outside the United States and Canada) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted positive opinions recommending approval of the combination of LENVIMA^? (marketed as Kisplyx^? in the European Union [EU] ?for the treatment of advanced renal cell carcinoma [RCC]), the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, plus KEYTRUDA^?, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A., for two different indications. One positive opinion is for the first-line treatment of adult patients with advanced RCC, and the other is for the treatment of adult patients with advanced or recurrent endometrial carcinoma (EC) who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and are not candidates for curative surgery or radiation. Decisions on the CHMP¡¯s recommendations will be given by the European Commission for marketing authorization in the EU, and are expected in the fourth quarter of 2021. If approved, this would be the first combination of an anti-PD-1 therapy with a tyrosine kinase inhibitor approved for the treatment of two different types of cancer in the EU.

The positive CHMP opinions are based on data from two pivotal Phase 3 trials: CLEAR (Study 307)/KEYNOTE-581 evaluating the combination in adult patients with advanced RCC and Study 309/KEYNOTE-775 evaluating the combination in certain patients with advanced EC.

In CLEAR/KEYNOTE-581, LENVIMA plus KEYTRUDA demonstrated statistically significant improvements versus sunitinib in the efficacy outcome measures of overall survival (OS), reducing the risk of death by 34% (HR=0.66 [95% CI, 0.49-0.88]; p=0.0049) versus sunitinib, and progression-free survival (PFS), reducing the risk of disease progression or death by 61% (HR=0.39 [95% CI, 0.32-0.49]; p<0.0001) with a median PFS of 23.9 months versus 9.2 months for sunitinib. Additionally, the confirmed objective response rate was 71% (95% CI: 66-76) (n=252) for patients who received LENVIMA plus KEYTRUDA versus 36% with sunitinib (95% CI: 31-41) (n=129).

In Study 309/KEYNOTE-775, LENVIMA plus KEYTRUDA demonstrated statistically significant improvements in the study¡¯s dual efficacy outcome measures of OS, reducing the risk of death by 38% (HR=0.62 [95% CI, 0.51-0.75]; p<0.0001) with a median OS of 18.3 months versus 11.4 months for chemotherapy (investigator¡¯s choice of doxorubicin or paclitaxel), and PFS, reducing the risk of disease progression or death by 44% (HR=0.56 [95% CI, 0.47-0.66]; p<0.0001), with a median PFS of 7.2 months versus 3.8 months for chemotherapy (investigator¡¯s choice of doxorubicin or paclitaxel).

¡°KEYTRUDA plus LENVIMA demonstrated a survival benefit for advanced renal cell carcinoma in the first-line setting and represents an important potential new treatment option for these patients. Additionally, KEYTRUDA plus LENVIMA is the first anti-PD-1 and tyrosine kinase inhibitor combination to demonstrate a survival benefit in advanced endometrial carcinoma patients, and the benefit was shown regardless of mismatch repair status,¡± said Dr. Gregory Lubiniecki, Vice President, Clinical Research, Merck & Co., Inc., Kenilworth, N.J., U.S.A. Research Laboratories. ¡°We are pleased that the CHMP has recognized the important role of the combination therapy in these difficult-to-treat cancers.¡±

¡°We appreciate the positive opinions rendered by the EU CHMP recommending approval of LENVIMA plus KEYTRUDA in advanced renal cell carcinoma and advanced endometrial carcinoma, underscoring the potential significance of the outcomes observed in the CLEAR/KEYNOTE-581 and Study 309/KEYNOTE-775 trials¡± said Dr. Takashi Owa, President, Oncology Business Group at Eisai. ¡°We are grateful to the patients who participated in these studies, their families and clinicians. Their commitment made these meaningful milestones possible.¡±

In CLEAR/KEYNOTE-581, the most common adverse reactions (¡Ý30%) for LENVIMA plus KEYTRUDA* were diarrhoea (61.8%), hypertension (51.5%) fatigue (47.1%), hypothyroidism (45.1%), decreased appetite (42.1%), nausea (39.6%), stomatitis (36.6%), proteinuria (33.0%), dysphonia (32.8%), and arthralgia (32.4%).

In Study 309/KEYNOTE-775, the most common adverse reactions of these patients (¡Ý20%) for LENVIMA plus KEYTRUDA* were hypertension (63%), diarrhoea (57%), hypothyroidism (56%), nausea (51%), decreased appetite (47%), vomiting (39%), fatigue (38%), decreased weight (35%), arthralgia (33%), proteinuria (29%), constipation (27%), headache (27%), urinary tract infection (27%), dysphonia (25%), abdominal pain (23%), asthenia (23%), palmar-plantar erythrodysaesthesia syndrome (23%), stomatitis (23%), anaemia (22%), and hypomagnesaemia (20%).

*According to the information listed in the SmPC (Summaries of Product Characteristics£©