A Phase III, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of Atezolizumab (Anti-PD-L1 Antibody) as Adjuvant Therapy in Patients with Renal Cell Carcinoma at High Risk of Developing Metastasis Following Nephrectomy

Status: 
Recruiting
Sponsor: 
Hoffmann-La Roche
Enrollment: 
664
Study Design: 
This phase III, randomized, double-blind, multicenter trial (IMmotion010) is enrolling patients with clear cell or sarcomatoid RCC at high risk for RCC recurrence after radical or partial nephrectomy, with lymphadenectomy allowed in select patients, high risk defined as T2N0M0 Fuhrman Grade 4, T3aN0M0 Fuhrman Grade 4 or higher, T3b/c & T4 with any Fuhrman grade, or any T stage or Fuhrman grade with lymph node positive disease. Similar to the KEYNOTE-564 trial, complete resection of limited synchronous or metachronous metastases is permitted. Patients are randomized 1:1 to receive either atezolizumab or placebo every 3 weeks for 16 cycles or 1 year unless there is unacceptable toxicity or disease progression. Patients will be stratified by stage and PD-L1 status.
Rationale: 
Much as the aforementioned study, this study seeks to evaluate the role of immune checkpoint inhibitor therapy in the adjuvant setting. Atezolizumab, an anti-PD-L1 antibody, has demonstrated activity in the metastatic setting in RCC, in particular in combination with bevacizumab in the IMmotion150 and IMmotion151 trials.
Endpoints: 
The primary endpoint of IMmotion010 will be DFS as assessed by independent review facility (IRF). The secondary endpoints will be overall survival, and investigator-assessed DFS. IRF-assessed and investigatory-assessed DFS will also be evaluated based on tumor-infiltrating immune cell (IC) levels.
Comments: 
The KEYNOTE-564 and IMmotion010 trials will evaluate the role of immune checkpoint inhibitor therapy after definitive surgical intervention, but the results of these trials will be of particular interest to contrast to the ongoing PROSPER trial which was discussed in the last issue of Kidney Cancer. PROSPER is based on the hypothesis that the primary tumor and its microenvironment is critical to the effectiveness of immune checkpoint inhibitor therapy; thus, that trial is administering nivolumab, an anti-PD-1 antibody, for two cycles prior to proceeding to nephrectomy. All three trials are evaluating DFS as a primary endpoint, though all will report OS as a secondary endpoint. The results of these trials may be revealing in terms of the interplay between the tumor microenvironment and immunotherapy, with potential to optimally treat localized RCC and reduce the risk of recurrence and mortality from the disease.