Phase III study of first-line pembrolizumab (pembro) plus lenvatinib (len) in patients (pts) with advanced urothelial carcinoma (UC) ineligible for platinum-based chemotherapy: LEAP-011.

Abstract

TPS597 Background: KEYNOTE-052 (NCT02335424) results led to pembro, a PD-1 inhibitor, to become the standard of care for cisplatin-ineligible pts with locally advanced or metastatic UC with tumors expressing PD-L1 and for pts unable to receive platinum-based chemotherapy regardless of PD-L1 status. Len, a potent, multiple-receptor, tyrosine kinase inhibitor has activity in multiple solid tumors. KEYNOTE-146 (NCT02501096) results showed promising efficacy and manageable safety with pembro+len in previously treated pts with advanced UC, regardless of PD-L1 status. Methods: LEAP-011 (NCT03898180) is a randomized phase 3 study to assess efficacy and safety of pembro+len, compared with pembro+placebo, in pts with advanced UC. An estimated 694 pts will be enrolled. Adults (≥18 years) with histologically confirmed locally advanced unresectable or metastatic UC who are either cisplatin-ineligible with tumors expressing PD-L1 (combined positive score [CPS] ≥10) or ineligible to receive any platinum-based chemotherapy are eligible. Pts are required to have an ECOG PS of 0-2 and provide tumor tissue for PD-L1 analysis. Previous treatment with systemic chemotherapy for advanced UC is not permitted, except in cases of recurrence after 1 year of platinum-based chemotherapy for either muscle-invasive bladder cancer (neoadjuvant) or after radical cystectomy (adjuvant). Pts will be randomly assigned 1:1 to receive pembro 200 mg IV every 3 weeks for up to 35 cycles (~2 y) plus either len 20 mg or placebo orally once daily. Pts will be stratified as follows: ineligible for any platinum containing chemotherapy and ECOG PS 2 (CPS ≥10 vs <10); cisplatin ineligibility and CPS ≥10 (ECOG 0-1 vs 2). Radiologic assessment will include CT/MRI of the chest, abdomen, and pelvis, and bone imaging. Responses will be assessed per RECIST v1.1 by blinded independent central review (BICR). Coprimary end points are PFS and OS. Secondary end points are objective response rate, duration of response, and disease control rate per RECIST v1.1 by BICR; patient-reported outcomes; and safety. Tissue-and blood-based biomarkers will be explored. Accrual began May 6, 2019. Clinical trial information: NCT03898180.