Lenvatinib And Stereotactic radiothErapy With pembRolizumab in Metastatic Kidney Cancer Patients

Metastatic clear cell renal cell carcinoma (mRCC) is sensitive to combination of lenvatinib and pembrolizumab. The CLEAR study showed positive results in patients with low tumor burden. However, around 20% of patients do not respond and have stable disease. In the VOLGA study, we demonstrated better outcomes in patients with irradiation of even a single lesion during targeted therapy. Thus, investigators hypothesize that stereotactic radiotherapy (SBRT) to multiple lesions in patients undergoing ongoing therapy with pembrolizumab and lenvatinib will increase the objective response rate, which may correlate with improved overall survival.

LASER is a randomized multicenter phase 2 study. Initially, all patients with histologically confirmed mRCC, the median sum of the diameters of target lesions ≥ 7 cm, ECOG 0-2, and the absence of prior systemic therapy for metastatic disease will receive a 12-week induction with lenvatinib and pembrolizumab, followed by radiological assessment according to RECIST 1.1 and allocation by outcome (response, stable disease, or disease progression). Patients with stable disease (SD) will be randomized in a 1:1 ratio into two groups: 1) lenvatinib + pembrolizumab + SBRT (N=27) or 2) lenvatinib + pembrolizumab alone (N=27). In the SBRT group, the choice of target for irradiation - up to 3 (three) lesions - is determined by a multidisciplinary team. The primary endpoint is the objective response rate (ORR) of unirradiated lesions after randomization among patients with stable disease (assessed every 12 weeks according to RECIST 1.1). The statistical hypothesis is based on an expected ORR of 15% in the control group versus 50% in the SBRT group. A two-sided α of 0.05 and a power of 80% require 27 patients in each group (54 randomized). The total enrollment will be 150 patients.

No informado en este registro.

Drug: Lenvatinib · Drug: Pembrolizumab · Radiation: Stereotactic Body Radiation Therapy (SBRT)

No informado en este registro.

Drug: Lenvatinib · Drug: Pembrolizumab

20 mg orally once daily.

200 mg intravenously every 3 weeks

The dosage regimen is determined by a radiation oncologist and depends on the location of the lesion.

Plazo: Percentage of patients with response at week 12

Objective response rate (ORR) of unirradiated lesions after randomization among patients with stable disease

Plazo: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.

No informado en este registro.

Plazo: From date of randomization until the date of death from any cause, whichever came first, assessed up to 60 months.

No informado en este registro.

Plazo: From the first response to the date of disease progression or death for any reason, whichever came first, assessed up to 36 months.

No informado en este registro.

Plazo: Percentage of stable irradiated lesions at week 12

No informado en este registro.

Plazo: Rate of treatment-related adverse events at week 24

No informado en este registro.

A Randomized Phase 2 Trial of Lenvatinib Plus Pembrolizumab With or Without Stereotactic Radiation Therapy in Patients With Clear-cell Metastatic Renal Cell Carcinoma, Low Tumor Burden, and Stable Disease.