Treatment with lenvatinib (Lenvima) and pembrolizumab (Keytruda) has shown promise in patients with metastatic clear cell renal cell carcinoma (mccRCC) who have already received an immune checkpoint inhibitor, according to an interim analysis of an ongoing study to be presented at the International Kidney Cancer Symposium, taking place in Miami from November 15-16.
“These are very dramatic results,” said study author Chung-Han Lee, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City. “It’s the first data for looking at any of the (tyrosine kinase inhibitor/immunotherapy) combinations after people have already progressed on a checkpoint inhibitor. It’s essentially the only data that we have for this type of combination in this space.”
The open-label study was originally designed as a phase Ib/II study for patients across multiple tumor types who had one or more prior lines of therapy with a checkpoint inhibitor, and involves up to 360 participants, including 33 patients in the mccRCC subgroup.
The patients were given 29 mg of lenvatinib orally each day, plus pembrolizumab intravenously at a dose of 200 mg every third week, until disease progression or treatment discontinuation.
The immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)-established progression-free survival was 11.3 months (95% CI, 7.3–not evaluable); the overall response rate among the entire treatment population was 64%; and the disease control rate in evaluable patients was 100%.
Eighteen of the 33 patients had grade 3 or 4 adverse events, the most common being diarrhea, fatigue, and dysphoria.
The results show there are options even after a single immune checkpoint inhibitor has been exhausted, said Lee.
“I think it becomes a really important question, because right now in the first-line setting a lot of people are either being treated with dual checkpoint inhibitors such as (ipilimumab [Yervoy]/nivolumab [Opdivo]) or are being treated with some TKI/(immunotherapy) combination,” Lee said in an interview with CancerNetwork®.
“What the protocol and the results of the clinical trial that we did really shows is that, in this space, we can still get quite impressive responses to a combination like lenvatinib plus pembrolizumab,” he added. “It really is promising – it really is the first prospective data that we have for this kind of combination in this setting – and it certainly is very exciting, and the adverse events are manageable.”
The trial will continue into 2020. Although it’s still too early to determine overall survival, the combination is also being tested as a first-line treatment in a phase III trial, Lee said.
“I think we’re very excited to see what the final results will end up being,” he added.
Lee C, Shah A, Makker V, et al. Phase 2 Study of Lenvatinib plus Pembrolizumab for Disease Progression after PD-1/PD-L1 Immune Checkpoint Inhibitor (ICI) in Metastatic Clear Cell (mcc) Renal Cell Carcinoma (RCC): Results of an interim analysis. Presented at: the 18th International Kidney Cancer Symposium; November 15-16, 2019; Miami.