Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial.

Abstract

BACKGROUND:

We assessed the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with previously treated metastatic adrenocortical carcinoma (mACC).

METHODS:

In this phase 1b expansion cohort, patients with mACC and prior platinum-based therapy received avelumab at 10 mg/kg intravenously every 2 weeks. Continuation of mitotane was permitted; however, mitotane levels during the study were not recorded. Tumor response was assessed by Response Evaluation Criteria In Solid Tumors v1.1.

RESULTS:

Fifty patients received avelumab and were followed for a median of 16.5 months. Prior treatment included ≥2 lines in 74.0%; mitotane was continued in 50.0%. The objective response rate (ORR) was 6.0% (95% CI, 1.3% to 16.5%; partial response in 3 patients). Twenty-one patients (42.0%) had stable disease as best response (disease control rate, 48.0%). Median progression-free survival was 2.6 months (95% CI, 1.4 to 4.0), median overall survival (OS) was 10.6 months (95% CI, 7.4 to 15.0), and the 1-year OS rate was 43.4% (95% CI, 27.9% to 57.9%). In evaluable patients with PD-L1+ (n = 12) or PD-L1- (n = 30) tumors (≥5% tumor cell cutoff), ORR was 16.7% vs 3.3% (P = .192). Treatment-related adverse events (TRAEs) occurred in 82.0%; the most common were nausea (20.0%), fatigue (18.0%), hypothyroidism (14.0%), and pyrexia (14.0%). Grade 3 TRAEs occurred in 16.0%; no grade 4 to 5 TRAEs occurred. Twelve patients (24.0%) had an immune-related TRAE of any grade, which were grade 3 in 2 patients (4.0%): adrenal insufficiency (n = 1), and pneumonitis (n = 1).

CONCLUSIONS:

Avelumab showed clinical activity and a manageable safety profile in patients with platinum-treated mACC.

TRIAL REGISTRATION:

Clinicaltrials.gov NCT01772004 ; registered January 21, 2013.

• Authors: Christophe Le Tourneau, Christopher Hoimes, Corrine Zarwan, Deborah J Wong, Sebastian Bauer, Rainer Claus, Martin Wermke, Subramanian Hariharan, Anja von Heydebreck, Vijay Kasturi, Vikram Chand, James L Gulley
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 6 Issue 1 Pg. 111 (10 22 2018) ISSN: 2051-1426 [Electronic] England
• PMID: 30348224 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• avelumab

Topics

• Adrenocortical Carcinoma (drug therapy, pathology)
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis