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