913P - Avelumab in patients with metastatic adrenocortical carcinoma (mACC): results from the JAVELIN Solid Tumor trial

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer Immunology and Immunotherapy
Endocrine Cancers
Presenter Christophe Le Tourneau
Citation Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371
Authors C. Le Tourneau1, C. Zarwan2, C. Hoimes3, D.J. Wong4, S. Bauer5, M. Wermke6, H.J. Grote7, A. von Heydebreck8, K. Chin9, J. Gulley10
  • 1Dept Of Medical Oncology, Institut Curie, 75248 cedex5 - Paris/FR
  • 2Medical Oncology, Lahey Hospital and Medical Center, Burlington/US
  • 3Hematology And Oncology, Case Western Reserve University and University Hospitals Seidman Cancer Center, 44106 - Cleveland/US
  • 4Department Of Medicine, University of California, Los Angeles Medical Center, 90024 - Los Angeles/US
  • 5Dept. Of Medical Oncology, University Hospital Essen Westdeutsches Tumorzentrum, 45122 - Essen/DE
  • 6Early Clinical Trial Unit, Universitätsklinikum Dresden, 01307 - Dresden/DE
  • 7Oncology, Merck KGaA, 64293 - Darmstadt/DE
  • 8Biostatistics, Merck KGaA, Darmstadt/DE
  • 9Immune-oncology, EMD Serono, Inc, 01821 - Billerica/US
  • 10Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD/US

Abstract

Background

Avelumab is a human anti–PD-L1 IgG1 antibody that has shown promising clinical activity in multiple tumor types, and is approved in the US for the treatment of metastatic Merkel cell carcinoma. Here, we report an updated analysis of avelumab in patients (pts) with mACC, representing the largest prospective monotherapy study performed to date in this rare cancer with limited therapeutic options.

Methods

In a phase 1b cohort (NCT01772004), pts with mACC and prior platinum-based therapy received avelumab at 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Prior and ongoing treatment with mitotane was permitted. Tumors were assessed every 6 wks (RECIST v1.1). Endpoints included safety (NCI-CTCAE v4.0), best overall response, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results

As of Dec 31, 2016, 50 pts from 6 countries received avelumab for a median of 3.4 mos (0.5–24.8). Median follow-up was 16.5 mos (11.7-27.6); 5 pts (10.0%) remained on treatment. Median age was 50 y (range 21–71) and median time since diagnosis of metastatic disease was 14.5 mos. 24 pts (48.0%) had received ≥2 prior lines of treatment for advanced disease (median 1, range 0–6). 41 pts (82.0%) had a treatment-related adverse event (TRAE) of any grade; the most common (>15%) were nausea (20.0%) and fatigue (18.0%). 8 pts (16.0%) had a grade ≥3 TRAE, of which only increased ALT (4.0%) occurred in > 1 pt. 12 pts (24.0%) had an immune-related AE of any grade. Confirmed ORR was 6.0% (3 partial responses; 95% CI 1.3–16.5); response was ongoing in 1 pt at data cutoff. 21 pts (42.0%) had stable disease as best response (disease control rate 48.0%). Median PFS was 2.6 mos (95% CI 1.4–4.0). Median OS was 10.6 mos (95% CI 7.4–not estimable) and the 12-mo OS rate was 47.0% (95% CI 31.8–60.9). Responses occurred in 2 pts with PD-L1+ tumors and 1 PD-L1 − (≥5% tumor cell cutoff). In PD-L1 + (n = 12) vs PD-L1 − (n = 30) subgroups, median PFS was 5.5 vs 1.7 mos (HR 0.66; 95% CI 0.3–1.4) and median OS was 14.4 vs 11.5 mos (HR 0.82; 95% CI 0.3–2.2), respectively.

Conclusions

Avelumab had a manageable safety profile and demonstrated clinical activity in pts with platinum-treated mACC.

Clinical trial identification

NCT: NCT01772004 Protocol: EMR 100070-001

Legal entity responsible for the study

Pfizer Inc., New York, NY, USA; Merck KGaA, Darmstadt, Germany.

Funding

Funding was provided by Pfizer Inc., New York, NY, USA and Merck KGaA, Darmstadt, Germany.

Disclosure

C. Le Tourneau: Provided a consulting role for MSD, Bristol-Myers Squib, Novartis and AstraZaneca and received honoraria from Merck Serono and AstraZaneca. C. Zarwan: Provided an advisory role for Revere Pharmaceutics and consulting for Perceptive Informatics. C. Hoimes: Provided an advisory role for Seattle Genetics and Eisai, and participated in speaker\'s bureau\'s for Bristol-Myers Squib and Genentech. D.J. Wong: Received research funding from Armo Biosciences, BioMed Valley Discoveries, Roche-Genentech, Merck, EMD Serono, Bristol-Meyers Squibb, KURA Oncology, AstraZeneca. Provided an advisory role for Bristol-Meyers Squibb. S. Bauer: Research support: Novartis, Blueprint Medicines, Ariad; Consultant: GSK, Novartis, Pfizer, Bayer, Fresenius, Lilly, Blueprint Medicines, Deciphera; Honoraria (CME): Pharmamar, GSK, Pfizer, Bayer; Travel support: Pharmamar, Bayer. M. Wermke: Received research funding from Novartis, Pfizer, Roche, Novartis, Roche, Boehringer Ingelheim and Celgene. Provided an advisory role for Roche, Novartis, Bristol-Myers Squib, AstraZeneca and received honoraria from Roche, Novartis, Boehringer Ingelheim. H.J. Grote: Employee of Merck KGaA, Darmstadt, Germany. A. von Heydebreck: Employee of Merck KGaA, Darmstadt, Germany and holds Merck KGaA, Darmstadt, Germany stock. K. Chin: Employee of EMD Serono Inc. All other authors have declared no conflicts of interest.