Interim results were announced today from the advanced renal cell carcinoma (RCC) cohort of Study 111, a Phase 1b/2 study investigating lenvatinib, a multiple receptor tyrosine kinase inhibitor (including fibroblast growth factor receptors), in combination with pembrolizumab in patients with selected solid tumours. 

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 ESMO 2017 Congress in Madrid, by Chung-Han Lee, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, who spoke with ecancer about the results here.

"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 Lee.

"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 tumour types."

Source: EISAI