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Phase II Study Supports Potential for Atezolizumab plus Bevacizumab for Locally Advanced or Metastatic Renal Cell Carcinoma

Hypothesis generating study in first line mRCC shows that two drugs can be combined with a manageable safety profile and encouraging efficacy
On 18 February 2017, Roche announced encouraging results from the phase II IMmotion150 study that compared atezolizumab plus

bevacizumab and atezolizumab monotherapy to

sunitinib alone in patients with previously untreated, locally advanced or metastatic renal cell carcinoma (mRCC). These results were presented at the 2017 Genitourinary Cancers Symposium (16-18 February, Orlando, USA). IMmotion150 is the first randomised clinical trial to evaluate the combination of atezolizumab and bevacizumab in mRCC. The study was designed to inform further clinical development of this combination and the study results reinforce the potential of this combination in this setting.
While targeting VEGF improves outcomes for mRCC patients, resistance invariably develops, often within the first year, the authors explained in study background.
IMmotion150 is a global, multicentre, open-label, randomised phase II study that was designed to evaluate the efficacy and safety of atezolizumab plus bevacizumab (arm A), atezolizumab alone (arm B) or sunitinib alone (arm C) in 305 patients with previously untreated, locally advanced or metastatic RCC. Patients in arm A received atezolizumab administered intravenously at 1200 mg every 3 weeks (6 week cycles) plus bevacizumab intravenously at 15 mg until disease progression or lack of clinical benefit. Patients in arm B received atezolizumab alone (until disease progression or lack of clinical benefit), and patients in arm C received sunitinib 50 mg orally daily for 4 weeks followed by 2 weeks rest until disease progression.
The co-primary endpoints were PFS per RECIST v.1.1 via Independent Review Facility (IRF) assessment in all randomised patients (ITT population) and in the PD-L1 selected (IC1/2/3) subgroup. PD-L1 expression was assessed on tumour-infiltrating immune cells (IC) with an investigational immunohistochemistry (IHC) test based on the SP142 antibody being developed by Roche Tissue Diagnostics. Secondary endpoints included IRF-assessed overall response rate (ORR) and duration of response (DoR), investigator-assessed PFS, ORR, DoR and safety, and overall survival (OS).
The study showed that patients whose cancer expressed PD-L1 and were treated with atezolizumab plus bevacizumab had a 36% reduction in the risk of their disease worsening or death compared to patients treated with sunitinib alone (median PFS 14.7 vs. 7.8 months; HR= 0.64; 95% CI 0.38, 1.08). No PFS advantage was observed compared to sunitinib in the ITT population (median PFS: 11.7 vs. 8.4 months; HR = 1.00; 95% CI 0.69, 1.45). Median DoR has not yet been reached after 20.7 months of follow-up across treatment arms. 
IMmotion150 was designed with planned crossover. Over three quarters (78%) of sunitinib patients (arm C) who progressed subsequently received atezolizumab plus bevacizumab (arm A).
The OS results were immature at time of analysis with only 35% of events having occurred. 
Adverse events in the atezolizumab plus bevacizumab arm were consistent with those observed in previous studies of each medicine. No new safety signals were identified. Frequency of all-grade treatment-related adverse events was similar between arms. The most common adverse events occurring in more than 20% of patients receiving atezolizumab plus bevacizumab and with a greater than 5% increase when compared to sunitinib included: arthralgia (38%), proteinuria (36%), epistaxis (28%), and pruritus (22%). Frequency of grade 3-4 adverse events regardless of relationship to treatment were similar between patients treated with atezolizumab plus bevacizumab (63%) and sunitinib (69%). Treatment-related grade 3-4 events reported in 40% of atezolizumab plus bevacizumab treated patients and 57% of sunitinib treated patients. One person who was treated with atezolizumab plus bevacizumab experienced intracranial haemorrhage that led to death. Fifteen of 101 patients (15%) treated with atezolizumab plus bevacizumab discontinued treatment for adverse events.
Roche is also evaluating atezolizumab plus bevacizumab vs. sunitinib in a phase III study (IMmotion151) in patients with previously untreated, locally advanced or metastatic RCC. A study of atezolizumab as adjuvant treatment for RCC began enrolling earlier this year.
Reference

McDermott DF, Atkins MB, Motzer RJ, et al. A phase II study of atezolizumab (atezo) with or without bevacizumab (bev) versus sunitinib (sun) in untreated metastatic renal cell carcinoma (mRCC) patients (pts). J Clin Oncol 35, 2017 (suppl 6S; abstract 431)

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