Findings from a planned interim analysis of the Ib/II Study 111 showed that lenvatinib (Lenvima) plus pembrolizumab (Keytruda) induced a disease control rate of 94% in patients with metastatic clear cell renal cell carcinoma (RCC) who regressed following treatment with a programmed cell death protein 1/programmed cell death-ligand 1 inhibitor.
“These are very dramatic results,” study author Chung-Han Lee, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, said in an interview with CancerNetwork® ahead of the International Kidney Cancer Symposium, held November 15-16, in Miami. “It’s the first data…looking at any of the (tyrosine kinase inhibitor [TKI]/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 metastatic clear cell RCC subgroup. Lee said the trial is still recruiting patients and hopes to eventually accrue a population of 100. Patients were assigned to 20 mg daily lenvatinib plus 200 mg intravenous pembrolizumab every 3 weeks until progression or toxicity.
The objective response rate (ORR) at week 24, the primary end point, was 61% (95% CI, 42%-77%). The confirmed ORR by investigator review was 64% (95% CI, 45%-80%) and was made up of all partial responses. An additional 10 patients (30%) had stable disease and 2 (6%) were not evaluable for response. The duration of response was 9.1 months (95% CI, 6.1-not evaluable). The median time to response in responders was 1.6 months (95% CI, 1.1-14.0). Progression-free survival was 11.3 months (95% CI, 7.3–not evaluable) using the immune-related Response Evaluation Criteria in Solid Tumors.
Lee stated that the safety results were “fairly characteristic” of patients treated with a VEGF/immune checkpoint inhibitor combination. Eighteen of the 33 patients had grade 3 or 4 adverse events, the most common being diarrhea, fatigue, and dysphoria. Six patients (18%) experienced any-grade hypothyroidism and 2 each (6%) experienced colitis, hyperthyroidism, or a severe skin reaction. One patient developed pneumonitis.
The results show that 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.
“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 is 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.
1. 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 inhibition (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, FL.