More than half of patients with metastatic clear cell renal cell carcinoma (RCC) treated with a combination of the tyrosine kinase inhibitor lenvatinib and the anti–PD-1 therapy pembrolizumab responded to treatment at week 24, according to interim results (abstract 8470) of a phase I/II study presented at the 2017 European Society for Medical Oncology (ESMO) Congress in Madrid. Responses, all of which were partial responses, occurred both in patients with treatment-naive disease and those with previously treated disease.
The multicenter, open label study included 30 patients with metastatic clear cell RCC. Patients were given 20-mg lenvatinib per day plus 200-mg pembrolizumab every 3 weeks, the maximum tolerated dose established in the phase Ib study (n = 8). The primary endpoint was objective response rate at 24 weeks.
The majority of patients (63%) enrolled had at least one prior therapy. More than one-half of patients with prior treatment had prior VEGF-targeted therapy.
At 24 weeks, the objective response rate was 63% (95% CI, 44%–80%) based on investigator-assessed immune-related RECIST. The disease control rate, combining complete response, partial response, and stable disease, was 96%.
Much of the data for secondary endpoints was not yet mature. The median progression-free survival and median duration of response was not reached.
The researchers looked at outcomes based on prior treatment. The objective response rate was 83% for patients with previously untreated disease, with a disease control rate of 100%. In patients with previously treated disease, the objective response rate was 50% with a disease control rate of 94%. The median duration of response in previously treated disease was 8.5 months.
“The observed efficacy in the metastatic RCC cohort of Study 111, particularly the 83% response rate among treatment-naive patients, provides clinical evidence of the antitumor activity of lenvatinib in combination with pembrolizumab in patients with RCC,” lead investigator Chung-Han Lee, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, said in a press release.
When evaluated by PD-L1 status, the objective response rate was 71% for patients with PD-L1–negative disease with a disease control rate of 100%. In PD-L1–positive disease, the objective response rate was lower, 58%, with a disease control rate of 91%.
The most common any-grade treatment-emergent adverse events were diarrhea, fatigue, hypothyroidism, nausea, and stomatitis. Sixteen patients had grade 3 treatment-emergent adverse events and two had grade 4 events. In addition, two patients had grade 5 events but these were related to disease progression and not considered to be related to the study drugs.
“These data are encouraging as we look to continue enrollment 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,” Lee said.