The newly launched phase 2 LenCabo study of lenvatinib with everolimus vs cabozantinib for the second- or third-line treatment of metastatic renal cell carcinoma.
The combination of lenvatinib (Lenvima) and everolimus (Afinitor) has the potential to prolong progression-free survival (PFS), compared with cabozantinib (Cabometyx), in patients with metastatic renal cell carcinoma (mRCC) who progressed on a PD-1/PD-L1 therapy.1
Standard-of-care frontline therapy for mRCC consists of immune checkpoint inhibitors and angiogenesis targeted therapy. After progression on first-line agents, many patients with mRCC are treated with cabozantinib or lenvatinib/everolimus, both of which have mechanisms of action that overlap with first-line immune checkpoint inhibitors. Moreover, the mechanisms of action for lenvatinib and cabozantinib are similar but not exact. Lenvatinib and cabozantinib have never been compared in a clinical trial.
The newly launched phase 2 LenCabo study (NCT05012371) of lenvatinib with everolimus vs cabozantinib as a second- or third-line treatment of mRCC, sponsored by MD Anderson Cancer Center and funded by Eisai Co., Ltd, will be the first study comparing lenvatinib and cabozantinib. The target enrollment is 90 patients with mRCC who received 1 to 2 prior therapies including a PD-1/PD-L1 inhibitor. Patients are required to have histologically confirmed disease, measurable disease per RECIST 1.1, and brain metastases must be stable at least 4 weeks before enrolling in the study. The study excludes patients who were previously treated with lenvatinib, a c-MET inhibitor, or an mTOR inhibitor, as well as had radiotherapy within 14 days or major surgery within 28 days of enrollment, active inflammatory bowel disease, or other uncontrolled medical conditions.
The study will assess the PFS as its primary end point. The study is 82% powered to detect a median PFS of 7.4 months in both arms and a median PFS of 12.8 months in the combination arm with a controlled type I error rate of 0.15. The interim analysis of the study will be conducted once 50 patients have been randomized.
The secondary end points of the study are objective response rate determined by the percentage of complete responses (CRs) and partial responses (PRs); disease control rate determined by the percentage of CRs, PRs, and patients with stable disease; health-related quality of life; safety defined by the number of grade 3/4 adverse events; and overall survival. As an exploratory end point, the study will evaluate whether alterations to c-MET, AXL, VEGF, mTOR, and FGFR correlate with treatment response.
Patients in the LenCabo study will be stratified by International Metastatic RCC Database Consortium risk group, and prior receipt of VEGF targeted therapy. The patients will be randomized 1:1 to receive lenvatinib/everolimus or cabozantinib. Treatment will commence once 90 patients have been enrolled. Lenvatinib will be administered at 18 mg daily in combination with 5 mg everolimus daily, compared with 60 mg cabozantinib daily. All patients will continue treatment until the study’s end or until disease progression or unacceptable treatment-related toxicity. Crossover is permitted in the study.
Currently, the trial is recruiting patients at MD Anderson Cancer Center. Two additional study sites, Moffitt Cancer Center and University of Virginia Emily Couric Clinical Cancer Center will be opened within 6 months.
Hahn AW, Chahoud J, Skelton WP, et al. A phase II study of lenvatinib plus everolimus versus cabozantinib in patients with metastatic renal cell carcinoma (mRCC) that progressed on a PD-1/PD-L1 checkpoint inhibitor (LenCabo). Presented at: 2022 International Kidney Cancer Symposium. November 4-5, 2022; Austin, TX. Abstract 51.