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Clinical Trial
. 2019 Jan 16;7(1):12.
doi: 10.1186/s40425-018-0459-y.

Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial

Ulrich Keilholz  1 , Janice M Mehnert  2 , Sebastian Bauer  3 , Hugues Bourgeois  4 , Manish R Patel  5 , Donald Gravenor  6 , John J Nemunaitis  7 , Matthew H Taylor  8 , Lucjan Wyrwicz  9 , Keun-Wook Lee  10 , Vijay Kasturi  11 , Kevin Chin  12 , Anja von Heydebreck  13 , James L Gulley  14
Affiliations
Clinical Trial

Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial

Ulrich Keilholz et al. J Immunother Cancer. .

Abstract

Background: We report phase 1b data from patients enrolled in the JAVELIN Solid Tumor clinical trial (NCT01772004) with unresectable stage IIIC or IV melanoma that had progressed after ≥1 line of therapy for metastatic disease.

Patients and methods: Patients received avelumab (10 mg/kg)-a human anti-PD-L1 antibody. Assessments included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety.

Results: As of December 31, 2016, 51 patients were treated and followed for a median of 24.2 months (range, 16.1-31.5). Most patients had cutaneous (n = 28 [54.9%]) or ocular (n = 16 [31.4%]) melanoma and had received a median of 2 prior lines of therapy (range, 0-4), including ipilimumab (n = 26 [51.0%]). The confirmed ORR was 21.6% (95% CI, 11.3-35.3; complete response, 7.8%; partial response, 13.7%). The median duration of response was not estimable (95% CI, 2.6 months-not estimable). Median PFS and OS were 3.1 months (95% CI, 1.4-6.3) and 17.2 months (95% CI, 6.6-not estimable), respectively. Subgroup analyses suggested meaningful clinical activity (ORR [95% CI]) in patients with non-ocular melanoma (31.4% [16.9-49.3]), PD-L1-positive tumors (42.1% [20.3-66.5]), or prior ipilimumab therapy (30.8% [14.3-51.8]). Thirty-nine patients (76.5%) had a treatment-related adverse event (TRAE), most commonly infusion-related reaction (29.4%), fatigue (17.6%), and chills (11.8%); 4 patients (7.8%) had a grade 3 TRAE. Five patients (9.8%) had an immune-related TRAE (all were grade 1/2). No grade 4 TRAEs or treatment-related deaths were reported.

Conclusion: Avelumab showed durable responses, promising survival outcomes, and an acceptable safety profile in patients with previously treated metastatic melanoma.

Trial registration: ClinicalTrials.gov identifier: NCT01772004 .

Keywords: Avelumab; Cutaneous melanoma; Immune checkpoint inhibitor; Ocular melanoma; PD-L1.

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Conflict of interest statement

Ethics approval and consent to participate

All patients were enrolled in accordance with approved protocols, international standards of good clinical practice, institutional review board approvals, and institutional safety monitoring. Written informed consent was provided.

Consent for publication

Not applicable.

Competing interests

UK has received honoraria from and is a member of advisory boards for AstraZeneca; Bristol-Myers Squibb; Merck, Sharp & Dohme; Merck KGaA; and Pfizer.

JMM reports consultancy for Merck, Sharp & Dohme and Amgen; reimbursement for travel and accommodations from EMD Serono and Merck, Sharp & Dohme; other relationships with Amgen, EMD Serono, and Merck KGaA; honoraria from Genentech and EMD Serono; JMM’s institution received research funding from Merck KGaA, Sanofi, Novartis, Polynoma, Immunocore, Amgen, and AstraZeneca.

SB has received honoraria from Pharmamar, GlaxoSmithKline, Pfizer, and Bayer; has received research support from Novartis, Blueprint Medicines, and Ariad; reports consultancy for GlaxoSmithKline, Novartis, Pfizer, Bayer, Fresenius, Lilly, Blueprint Medicines, and Deciphera; and received travel support from Pharmamar and Bayer.

HB has nothing to disclose.

MRP is a member of an advisory board for Guardant and speaker’s bureau for Exelixis, Bristol-Myers Squibb, Medivation, Genentech, and Gilead.

DG has nothing to disclose.

JJN has nothing to disclose.

MHT has received honoraria from Blueprint Medicines, Trillium Pharma, Bristol-Myers Squibb, and Eisai; is a member of an advisory board for Blueprint Medicines and speaker’s bureau for Eisai; and reports consultancy for Trillium Pharma and Bristol-Myers Squibb.

LW reports consultancy for and has received honoraria from Amgen, Roche, and Merck.

KWL’s institution received research funds from AstraZeneca, Daiichi Sankyo, Five Prime Therapeutics, Green Cross Corp., Macrogenics, Merck KGaA, Merck & Co., Ono Pharmaceutical and Taiho Pharmaceutical.

VK is employed by EMD Serono.

KC is employed by EMD Serono.

AvH is employed by Merck KGaA.

JLG has nothing to disclose.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Time to and duration of response (a) and change in tumors in all patients (b)
Fig. 2
Fig. 2
PFS (a) and OS (b) in all patients
Fig. 3
Fig. 3
PFS (a) and OS (b) in patients with non-ocular and ocular melanoma
Fig. 4
Fig. 4
Best change in sum of target lesion diameters from baseline (a), and PFS (b) and OS (c) according to tumor PD-L1 expression status at 1% cutoff in evaluable patients
See this image and copyright information in PMC

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