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Early Avelumab Plus Axitinib Findings ‘Encouraging’ For Treatment-Naive Advanced RCC

JAVELIN Renal 100 results indicate that avelumab plus axitinib may have a manageable safety profile as a first-line therapy for advanced renal cell carcinoma
14 Mar 2018
Anticancer Agents;  Renal Cell Cancer;  Therapy;  Biological Therapy
By Lynda Williams, Senior medwireNews Reporter

medwireNews: A phase Ib trial has raised the possibility of combining the VEGFR tyrosine kinase inhibitor axitinib with the PD-L1 inhibitor avelumab as a first-line treatment option for patients with advanced renal cell carcinoma (RCC) with a clear cell component.

Preliminary results from the JAVELIN Renal 100 study may show “encouraging antitumour activity with a manageable adverse event profile”, suggest Toni Choueiri, from Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, Massachusetts, USA, and team.

Dose-limiting toxicity, namely grade 3 proteinuria, was reported in one of the six patients enrolled in the dose-finding phase, all of whom were given axitinib alone at a dose of 5 mg twice daily for 7 days and then in combination with avelumab 10 mg/kg given every 2 weeks. 

A further 49 patients were enrolled into the dose-expansion phase of the trial, 10 of whom received a 7-day axitinib run-in period before combination therapy, while the remainder began combination therapy immediately.

Collating together safety information for all 55 patients, 58% had experienced grade 3 or more severe treatment-related adverse events, most commonly hypertension (29%), elevations in amylase (8%), lipase (8%), and alanine aminotransferase (ALT; 7%), and palmar–plantar erythrodysaethesia syndrome (7%).  

Serious adverse events related to treatment were reported in 22% of patients, including two cases of elevated ALT. Avelumab was discontinued by 13% of patients, attributed to elevated ALT in two cases, while 7% discontinued axitinib. 

Of the six patients who died before data cutoff, five deaths were attributed to disease progression and one to treatment-related autoimmune myocarditis. 

“[T]he adverse events observed with combination therapy in this study were largely consistent with the known safety profiles of avelumab when used alone or combined with pembrolizumab and axitinib in phase 1/2 studies”, the researchers write in The Lancet Oncology.

An objective response was confirmed in 100% of the first six patients and 53% of the dose-expansion group. This gave an overall rate of 58% including a complete response in three (6%) patients, two of whom had lymph node involvement. Disease control was achieved in 78% of the patients. 

Objective responses were recorded after a median of 6.8 weeks but as responses were ongoing in 24 patients at the time of data cutoff, the median duration of response is yet unknown, Toni Choueiri et al comment.

“These findings support the pivotal, randomised, phase 3 JAVELIN Renal 101 trial, which is comparing combined avelumab and axitinib with sunitinib monotherapy as first-line treatment for advanced renal-cell carcinoma,” the authors conclude.


Choueiri TK, Larkin J, Oya M, et al. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. Lancet Oncol; Advance online publication 9 March 2018.
DOI: https://doi.org/10.1016/S1470-2045(18)30107-4

Last update: 14 Mar 2018

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group

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