Combination Data for Lenvatinib and Pembrolizumab Demonstrate Notable Response Rates for Patients with Advanced Renal Cell Carcinoma

HATFIELD, England, September 9, 2017 /PRNewswire/ --

FOR EMEA MEDICAL MEDIA ONLY - NOT FOR SWISS/AUSTRIAN JOURNALISTS 

• Updated results of advanced RCC cohort from Study 111 support continued investigation of first-line use of the combination in ongoing Phase III study (CLEAR) 
• Phase Ib/II results to be presented in an oral proffered paper session on Saturday, 9 September at 9:15 a.m. CEST at European Society for Medical Oncology (ESMO) 2017 Congress

Eisai today announced interim results from the advanced renal cell carcinoma (RCC) cohort of Study 111 of Kisplyx^® (lenvatinib) in combination with the Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside of the United States and Canada) anti-PD-1 therapy, pembrolizumab (KEYTRUDA^®). The results demonstrate that the combination achieved a confirmed objective response rate (ORR) at week 24 of 63% (95% CI: 44 - 80), and disease control rate (DCR, complete response [CR] + partial response [PR] + stable disease [SD]), a secondary endpoint, was 96% (including 33% SD [n=10]).^[1] No new safety signals were found and toxicities were managed with supportive medications, dose interruptions/reductions or drug withdrawal.^[1] These results will be presented in an oral proffered paper session today (Abstract No. 847O) at the ESMO 2017 Congress in Madrid, Spain.

Study 111 is a Phase Ib/II study exploring the potential of combination treatment with lenvatinib and pembrolizumab in patients with selected solid tumours. Interim results reported at the ESMO 2017 Congress are taken from the cohort of both treatment-naive and previously treated patients with metastatic clear cell RCC (n=30).^[1] Lenvatinib and pembrolizumab are not currently approved for use in combination.

"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-tumour activity of lenvatinib in combination with pembrolizumab in patients with RCC," said Chung-Han Lee, MD, PhD, Memorial Sloan Kettering Cancer Centre, New York, and lead investigator. "These data are encouraging as we look to continue enrolment in the CLEAR trial, a Phase III 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."

The confirmed objective response rate at week 24, the primary endpoint of the study, was 63% (95% CI: 44 - 80) based on investigator-assessed immune-related RECIST.^[1] Secondary endpoints include ORR (measured beyond week 24), progression-free survival (PFS), duration of response (DOR) and safety and tolerability.^[1] 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: 9.7 - NE) and median DOR was not reached (95% CI: 8.4 - NE). The most common any-grade treatment-emergent adverse events (TEAEs) for the combination regimen were diarrhoea, fatigue, hypothyroidism, stomatitis, nausea and hypertension.

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: 8.4 - 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).

"Results from this second cohort from Study 111 for lenvatinib in combination with pembrolizumab are very encouraging with high response rates among patients with a difficult-to-treat, advanced stage cancer," said Gary Hendler, Chairman & CEO EMEA, Chief Commercial Officer, Oncology Business Group at Eisai. "These clinical data, in addition to data from the metastatic endometrial cancer cohort presented earlier this year, reinforce the importance of lenvatinib as a treatment option and its potential in combination regimens across multiple tumour types."

The Phase III 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 clinicaltrials.gov for more information.

Eisai is dedicated to the discovery, development and production of innovative oncology therapies that can make a difference and impact the lives of patients and their families. This passion for people is part of Eisai's human health care (hhc) mission, which strives to better understand the needs of patients and their families to increase the benefits health care provides.

KEYTRUDA^® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Notes to Editors 

About Study 111^[1]

Study 111 is a multicentre, open-label, single-arm Phase Ib/II basket trial of the combination of lenvatinib (20 mg/day) with pembrolizumab (200 mg intravenously every three weeks) in patients with selected solid tumours. The primary endpoint of the Phase Ib study was to determine the maximum tolerated dose of pembrolizumab and lenvatinib in combination. The primary endpoint of the Phase II study is investigator-assessed ORR based on immune-related RECIST criteria 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.

Seven patients experienced serious TEAEs; the only serious TEAE experienced by more than one patient was increased lipase.

About Renal Cell Carcinoma 

RCC is thought to occur in a variety of specialised cells located along the length of the nephron in the lining of the tubules in the kidney.^[2] RCC represents 2-3% of all adult cancer diagnoses^[3]and unfortunately more than 30% of patients with RCC do not survive.^[2]

About Lenvatinib  

Lenvatinib, discovered and developed by Eisai, is an oral multikinase inhibitor of vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor-alpha, and RET and KIT proto-oncogenes.^[4][5]  Lenvatinib is approved in the European Union (EU) for specific patient populations:

Lenvatinib is indicated:

• In the EU under the brand name Lenvima^® for the treatment of adult patients with progressive, locally advanced or metastatic, differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC) refractory to radioactive iodine (RAI).^[6] 
• In the EU and Switzerland under the brand name Kisplyx^® and Lenvima^® elsewhere, in combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior vascular endothelial growth factor (VEGF)-targeted therapy.^[7]

About Eisai Co., Ltd. 

Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realise our hhc philosophy by delivering innovative products in various therapeutic areas with high unmet medical needs, including Oncology and Neurology.

As a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries. 

For more information about Eisai Co., Ltd., please visit www.eisai.com.

References 

1. Lee C-H, et al. A Phase 1b/2 Trial of Lenvatinib Plus Pembrolizumab in Patients with Renal Cell Carcinoma. European Society for Medical Oncology annual meeting 2017; Abstract No. 847O.

2. Cairns P. (2011) Renal Cell Carcinoma. Cancer Biomarkers. 9(1-6), 461-473.

3. Greef B, et al. (2016) Medical treatment of renal cancer: new horizons. British Journal of Cancer. 115, 505-516.

4. Matsui J, et al. (2008) E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. International Journal of Cancer. 122, 664-671.

5. Okamoto K, et al. (2015) Distinct Binding Mode of Multikinase Inhibitor Lenvatinib Revealed by Biochemical Characterization. ACS Medicinal Chemistry Letter. 6(1), 89-94.

6. Eisai. (September 2017) Lenvima® (lenvatinib) Summary of Product Characteristics . Available from:  www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003727/WC500188674.pdf [Accessed September 2017].  

7. Eisai. (July 2017) Kisplyx® (lenvatinib) Summary of Product Characteristics. Available from:  www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004224/WC500216237.pdf [Accessed September 2017].  

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