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15-11-2019 | Renal cell carcinoma | At a glance | Article

At a glance: The IMmotion RCC trials

Here we provide a quick-access guide to the IMmotion clinical trials of the PD-L1 inhibitor atezolizumab in the renal cell carcinoma (RCC) setting. There are currently three trials, all of which are sponsored by Hoffmann-La Roche.

IMmotion150: Published
 

Phase 2

Patient population: Treatment-naïve, inoperable, locally advanced or metastatic RCC

Treatment: Atezolizumab 1200 mg plus bevacizumab 15 mg/kg every 3 weeks; atezolizumab alone; sunitinib 50 mg/day for 4 consecutive weeks of every 6-week cycle

https://clinicaltrials.gov/ct2/show/NCT01984242

Atezolizumab – either in combination with bevacizumab or alone – did not significantly improve progression-free survival (PFS) relative to sunitinib in the intention-to-treat (ITT) population. But the co-primary endpoint of PFS in patients with PD-L1 expression on at least 1% of tumor-infiltrating immune cells was significantly better with atezolizumab plus bevacizumab than sunitinib, with a hazard ratio (HR) for progression or death of 0.64, although again the atezolizumab alone and sunitinib groups were comparable.

The IMmotion150 researchers also identified gene expression signatures – such as the T-effector and angiogenesis signatures – that correlated with response to treatment, both within and across treatment arms.

These primary and biomarker results were published in Nature Medicine.

The trial permitted crossover of patients in either monotherapy arm to receive atezolizumab–bevacizumab, and preliminary data reported at the 2017 ASCO Annual Meeting  showed the antitumor activity of the combination in the second line also.

Pooled analysis of the safety data from IMmotion150 and IMmotion151, presented at the ESMO Congress 2018, confirmed the favorable safety profile of atezolizumab plus bevacizumab, with fewer grade 3 or 4 treatment-related adverse events (40 vs 54%) and fewer discontinuations (5 vs 8%) versus sunitinib.

Related news story: Combining checkpoint blockade with targeted therapy in first-line advanced RCC

Mmotion151: Published
 

Phase 3

Patient population: Treatment-naïve, inoperable, locally advanced or metastatic RCC

Treatment: Atezolizumab 1200 mg plus bevacizumab 15 mg/kg every 3 weeks; sunitinib 50 mg/day for 4 consecutive weeks of every 6-week cycle

https://clinicaltrials.gov/ct2/show/NCT02420821

As reported in The Lancet, this trial met one of its co-primary endpoints, showing a significant boost with the combination versus sunitinib in PFS in the PD-L1-positive (≥1%) population, at an HR for progression or death of 0.74. Data for the other primary endpoint – overall survival in the ITT population – were not mature at the time of analysis, but the secondary endpoint of PFS in these patients was prolonged with atezolizumab–bevacizumab relative to sunitinib (HR=0.83).

Patient-reported outcomes from the trial – presented at the 2018 ASCO Annual Meeting – also favored the atezolizumab–bevacizumab combination, and most recently, subgroup analyses reported at the 2019 ASCO Annual Meeting showed a significant PFS benefit with the combination for patients with sarcomatoid histology tumors (HR=0.52 vs sunitinib).

The molecular correlates of response identified in IMmotion150 were validated. As reported at the ESMO Congress 2018, high expression of the T-effector gene signature was linked to longer PFS with atezolizumab–bevacizumab versus sunitinib, while high levels of the angiogenesis signature were associated with improved response to sunitinib.

Pooled analysis of the safety data from IMmotion150 and IMmotion151, presented at the ESMO Congress 2018, confirmed the favorable safety profile of atezolizumab–bevacizumab, with fewer grade 3 or 4 treatment-related adverse events (40 vs 54%) and fewer discontinuations (5 vs 8%) versus sunitinib.

Related news stories:

IMmotion010: Ongoing
 

Phase 3

Patient population: RCC at high risk for recurrence after nephrectomy

Treatment: Atezolizumab 1200 mg every 3 weeks; placebo

https://clinicaltrials.gov/ct2/show/NCT03024996

This placebo-controlled trial is investigating the efficacy and safety of adjuvant atezolizumab in patients with a high recurrence risk following radical or partial nephrectomy. The primary endpoint of the study is disease-free survival.

By Shreeya Nanda

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

This independent article was supported by an educational grant from Pfizer and Merck KGaA

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