IMvigor130: A Randomized, Phase III Study Evaluating First-Line (1L) Atezolizumab (atezo) As Monotherapy and in Combination with Platinum-Based Chemotherapy (chemo) in Patients (pts) with Locally Advanced or Metastatic Urothelial Carcinoma (Muc).

TPS4589 Background: Platinum-based chemo is the standard of care for most pts with untreated mUC, although clinical outcomes remain poor. Atezo (anti–PD-L1) was approved in the United States, European Union and elsewhere as monotherapy in both the 1L cisplatin (cis)–ineligible and post-platinum settings based on the single-arm, Phase II IMvigor210 trial. Data from other tumor types (e.g., NSCLC and TNBC) suggest that atezo may be tolerable when combined with chemo. Here we describe IMvigor130, a Phase III trial designed to evaluate the efficacy and safety of 1L atezo given alone or in combination with platinum-based chemo vs placebo and chemo, in pts with locally advanced or mUC. Methods: Across 35 countries, IMvigor130 (NCT02807636) is enrolling ≈ 1200 pts with histologically documented advanced or mUC (T4b, any N; or any T, N2-3; M1, stage IV) of the bladder, urethra, renal pelvis or ureters who have not received prior chemo for advanced disease. Eligible pts have measurable disease (per RECIST v1.1), ECOG PS 0-2 and a tissue sample for PD-L1 testing (VENTANA SP142 IHC assay). IMvigor130 was initially designed to enroll only cis-ineligible pts but was amended to include all platinum-eligible pts. Pts are randomized 1:1:1 to: (A) atezo + chemo (gemcitabine [gem] + cis or carboplatin [carbo]), (B) atezo alone or (C) placebo + chemo at the following doses (starting day 1 of a 21-day cycle): atezo (or placebo) 1200 mg IV q3w, gem 1000 mg/m2 on days 1 and 8, carbo AUC 4.5 q3w, cis 70 mg/m2 q3w. Atezo and chemo are administered, in the absence of unacceptable toxicity, until RECIST v1.1 progressive disease. Randomization is stratified by PD-L1 status on immune cells, number of Bajorin risk factors or liver metastases and investigator's chemo choice. The co-primary endpoints are PFS and OS in Arm A vs Arm C in the ITT population and OS in Arm B vs Arm C in the ITT population. Key secondary efficacy endpoints include investigator-assessed ORR, DOR and PFS per RECIST v1.1 (for atezo vs placebo + chemo arms). Safety, biomarkers and other exploratory endpoints will also be evaluated. Clinical trial information: NCT02807636.