Combination of Lenvatinib and Pembrolizumab Results in Notable Response Rates for Patients with Advanced Renal Cell Carcinoma Based on Interim Analysis of Ongoing Phase 1b/2 Trial

- Updated results of advanced RCC cohort from Study 111 support continued investigation of first-line use of the combination in ongoing Phase 3 CLEAR study

- Phase 1b/2 results presented in an oral proffered paper session on Saturday, Sept. 9 at 10:15 a.m. CEST at ESMO 2017 Congress

WOODCLIFF LAKE, NJ, USA I September 10, 2017 I Eisai Inc. today announced interim results from the advanced renal cell carcinoma (RCC) cohort of Study 111, a Phase 1b/2 study investigating lenvatinib (marketed as Lenvima® in the U.S. and Japan and as Kisplyx® for RCC in the EU), a multiple receptor tyrosine kinase inhibitor (including fibroblast growth factor receptors [FGFR] 1 – 4), in combination with the Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the United States and Canada) anti-PD-1 therapy, pembrolizumab (marketed as KEYTRUDA®), in patients with selected solid tumors. In this cohort of both treatment-naïve and previously treated patients with metastatic clear cell RCC (n=30), the confirmed objective response rate (ORR) at week 24, the primary endpoint of the study, was 63% (95% CI: 44 – 80) based on investigator-assessed immune-related RECIST, all of which were partial responses (PR) (n=19), and disease control rate (DCR, complete response [CR] + PR + stable disease [SD]), a secondary endpoint, was 96% (including 33% SD [n=10]). No new safety signals were identified and toxicities were managed with supportive medications, dose interruptions/reductions or drug withdrawal. Lenvatinib and pembrolizumab are not approved for use in combination. These results were presented in an oral proffered paper session today at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain (Abstract No. 847O).  

"The observed efficacy in the metastatic RCC cohort of Study 111, particularly the 83% response rate among treatment-naïve patients, provides clinical evidence of the anti-tumor activity of lenvatinib in combination with pembrolizumab in patients with RCC," said Chung-Han Lee, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, and lead investigator. "These data are encouraging as we look to continue enrollment in the CLEAR trial, a Phase 3 trial evaluating the combination of this TKI and anti-PD-1 therapy in previously untreated patients with advanced RCC, and better understand how these results may translate to a larger group of patients with this type of cancer."

Secondary endpoints include ORR (measured beyond week 24), progression-free survival (PFS), DCR, duration of response (DOR) and safety and tolerability. ORR measured beyond week 24 remained the same as ORR measured at week 24. Median PFS was not reached at follow up of 9.7 months (95% CI: 9.9 – NE) and median DOR was not reached (95% CI: 8.4 – NE). The most common treatment-emergent adverse events (TEAE), any-grade, for the combination regimen were diarrhea, fatigue, hypothyroidism, stomatitis, nausea and hypertension. Sixteen patients experienced grade 3 TEAEs (the most common were increased lipase and hypertension) and two patients had grade 4 events. Two patients had grade 5 events, both of which were related to disease progression and not considered related to study drugs.

When evaluated based on treatment line, ORR was 83% (95% CI: 52 – 98) for previously-untreated patients (n=12) and DCR was 100% (83% PR [n=10]; 17% SD [n=2]). Median DOR was not reached (95% CI: 10.3 – NE). In previously treated patients (n=18), ORR was 50% (95% CI: 26 – 74) and DCR was 94% (50% PR [n=9]; 44% SD [n=8]). Median DOR was 8.5 months (95% CI: 3.5 – NE).

When evaluated by PD-L1 status, ORR was 71% (95% CI: 42 – 92) for patients with negative PD-L1 status (n=14) and DCR was 100% (71% PR [n=10]; 29% SD [n=4]). Median DOR was not reached (95% CI: 8.4 – NE). In patients with positive PD-L1 status (n=12), ORR was 58% (95% CI: 28 – 85) and DCR was 91% (58% PR [n=7]; 33% SD [n=4]). Median DOR was 10.3 months (95% CI: 3.5 – 10.3).

"This is the second cohort from Study 111 in which the combination of lenvatinib and pembrolizumab resulted in high response rates among patients with a difficult-to-treat, advanced stage cancer," said Alton Kremer, MD, PhD, Chief Clinical Officer and Chief Medical Officer, Oncology Business Group at Eisai. "The data to be presented today at ESMO, coupled with the data from the metastatic endometrial cancer cohort presented at ASCO, contribute to our body of knowledge as we continue to study this combination across multiple tumor types."

Lenvima (lenvatinib) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer. Lenvima (marketed as Kisplyx® for RCC in the EU) is also indicated in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy. This release discusses an investigational use for FDA-approved products. Lenvatinib is not approved for use in combination with pembrolizumab. This release is not intended to convey any conclusions about efficacy or safety of lenvatinib, pembrolizumab or any combination of these two agents. There is no guarantee that any investigational uses of such FDA-approved products will successfully complete clinical development or gain FDA approval.

The Phase 3 CLEAR trial (NCT02811861) evaluating lenvatinib plus pembrolizumab and lenvatinib plus everolimus versus sunitinib as first-line therapy in patients with advanced RCC is currently enrolling; please visit for more information.

About Study 111

Study 111 is a multicenter, open-label, single-arm Phase 1b/2 basket trial of the combination of lenvatinib (20 mg/day) with pembrolizumab (200 mg intravenously every 3 weeks) in patients with selected solid tumors. The primary endpoint of the Phase 1b study was to determine the maximum tolerated dose of pembrolizumab and lenvatinib in combination. The primary endpoint of the Phase 2 study is investigator-assessed ORR based on immune-related RECIST at week 24. The secondary endpoints include progression-free survival, duration of response, disease control rate, and clinical benefit rate. Thirty patients with metastatic clear cell RCC were evaluated in the RCC cohort. The study is being conducted under an existing clinical trial collaboration agreement between the two companies.

About Renal Cell Carcinoma

Renal cell carcinoma (RCC), also known as renal cell cancer or renal cell adenocarcinoma, is the most common type of kidney cancer, representing about 90% of cases in the United States. Renal cell carcinoma occurs when malignant cells are found in the lining of the tubules in the kidney. While RCC usually grows as a single tumor within a kidney, there may also be two or more tumors in one or both kidneys. In 2017, it is estimated that there will be approximately 64,000 new cases of kidney cancer, and about 14,400 people will die from the disease. Approximately 16% of patients with RCC will have metastases at diagnosis, and as many as 40% will demonstrate metastasis after primary surgical treatment for localized RCC. With a 5-year survival rate ranging from 5% to 12%, the prognosis for these patients is poor.

About Lenvima® (lenvatinib)

Lenvima® (lenvatinib) is a kinase inhibitor that is indicated for:

  • Differentiated Thyroid Cancer (DTC): single agent for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC.
  • Renal Cell Cancer (RCC): in combination with everolimus for patients with advanced RCC following one prior anti-angiogenic therapy.

Lenvatinib, discovered and developed by Eisai, is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1-3. Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. The combination of lenvatinib and everolimus showed increased anti-angiogenic and anti-tumor activity as demonstrated by decreased human endothelial cell proliferation, tube formation, and VEGF signaling in vitro and tumor volume in mouse xenograft models of human renal cell cancer greater than each drug alone.

About Eisai Inc.

At Eisai Inc., human health care (hhc) is our goal. We give our first thought to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs.

Eisai is a fully integrated pharmaceutical business that operates in two global business groups: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Each group functions as an end-to-end global business with discovery, development, and marketing capabilities. Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery labs are in Massachusetts and Pennsylvania; and our global demand chain organization resides in Maryland and North Carolina. To learn more about Eisai Inc., please visit us at


La Merie Biologics

FREE Weekly News Bulletin

Sign Up

2017 Sales ofAntibodies & Proteins

New Product Alert

For La Merie Publishing

Sign Up