The JAVELIN clinical trials are investigating the efficacy and safety of the PD-L1 inhibitor avelumab in various tumor types and settings. Here we round up the data thus far available from the trials focusing on renal cell carcinoma (RCC).
JAVELIN Renal 101: Published
Phase III | ||
Patient population: Treatment-naïve, clear-cell, advanced RCC | Treatment: Avelumab 10 mg/kg every 2 weeks plus axitinib 5 mg twice daily; sunitinib 50 mg/day for 4 consecutive weeks of every 6-week cycle | Sponsor: Pfizer |
In JAVELIN Renal 101, the co-primary endpoint of progression-free survival (PFS) in patients with PD-L1-positive tumors was significantly improved with avelumab–axitinib versus sunitinib, with a reduction in the risk for progression or death of 39%. The data for the other primary endpoint – overall survival in PD-L1-positive patients – were not mature at the time of data cutoff and publication in The New England Journal of Medicine.
Biomarker analyses from the trial – presented at the 2019 ASCO Annual Meeting – provided additional insight into the response elicited by the combination of the PD-L1 inhibitor and VEGF–tyrosine kinase inhibitor. The researchers reported tumor-infiltrating T-cell data and gene expression analysis that could help predict response to the dual therapy.
Subgroup analyses reported at the ESMO Congress 2019 showed better outcomes with the combination than sunitinib in individuals with sarcomatoid histology tumors and those who did not receive upfront cytoreductive nephrectomy. In line with a previous report, elevated CD8 expression on tumor-infiltrating cells was associated with improved PFS in both subgroups, but the JAVELIN Renal 101 gene signature was not predictive for the no upfront surgery group.
Related content:
- First-line avelumab–axitinib outperforms sunitinib in advanced RCC
- Expert comment on the JAVELIN Renal 101 trial
- JAVELIN Renal 101 biomarker analysis may help personalize patient care
- USA approves first-line avelumab–axitinib for advanced RCC
- JAVELIN Renal 101 subanalyses add to evidence for avelumab plus axitinib
- Researcher comment: JAVELIN Renal 101 – Combination approach for advanced RCC patients without upfront cytoreductive nephrectomy
- Expert highlights: RCC immunotherapy at ESMO 2019
JAVELIN Renal 100: Published
Phase I | ||
Patient population: Treatment-naïve, clear-cell, advanced RCC | Treatment: Avelumab 10 mg/kg every 2 weeks plus axitinib 5 mg twice daily | Sponsor: Pfizer |
As reported in The Lancet Oncology, 58% of the trial participants achieved an objective response, the median duration of which was unreached at the time of analysis (median follow-up of 52.1 weeks). The disease control rate was 78%.
Related news stories:
- Promising early data reported for avelumab plus axitinib in advanced RCC
- Combining checkpoint blockade with targeted therapy in first-line advanced RCC
JAVELIN Solid Tumor: Ongoing
Phase I | ||
Patient population: Locally advanced or metastatic solid tumors | Treatment: Avelumab 1, 3, 10, or 20 mg/kg every 2 weeks | Sponsor: EMD Serono |
This study is investigating the PD-L1 inhibitor in patients with various locally advanced or metastatic solid tumors – including RCC – for which no standard therapy is available or has failed.
The initial dose-escalation phase demonstrated an acceptable safety profile for avelumab, and the dose selected for further development was 10 mg/kg every 2 weeks. These results appeared in The Lancet Oncology.
Data from the RCC cohort, presented at the ESMO 2018 Congress, indicated promising efficacy for avelumab monotherapy in both the first- and second-line settings, with respective objective response rates of 16.1% and 10.0%.
Summary of approvals |
In May 2019, the US FDA decided in favor of avelumab–axitinib for the front-line treatment of advanced RCC. The recommended doses for both drugs are the same as the ones used in the clinical trials. Related news story: USA approves first-line avelumab–axitinib for advanced RCC |
The EMA gave the nod to the combination in September 2019. Avelumab plus axitinib is indicated for adult patients who have not received prior treatment for advanced RCC. Related news story: Avelumab indication extended in Europe to advanced RCC |
By Shreeya Nanda
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This independent article was supported by an educational grant from Pfizer and Merck KGaA