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