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Clinical Trial
. 2019 Feb 4;7(1):30.
doi: 10.1186/s40425-019-0508-1.

Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial

Hyun Cheol Chung  1 , Hendrik-Tobias Arkenau  2 , Jeeyun Lee  3 , Sun Young Rha  4 , Do-Youn Oh  5 , Lucjan Wyrwicz  6 , Yoon-Koo Kang  7 , Keun-Wook Lee  8 , Jeffrey R Infante  9 , Sung Sook Lee  10 , Margaret Kemeny  11 , Ulrich Keilholz  12 , Bohuslav Melichar  13 , Alain Mita  14 , Ruth Plummer  15 , Denis Smith  16 , Arnold B Gelb  17 , Huiling Xiong  17 , Janet Hong  17 , Vikram Chand  17   18 , Howard Safran  19
Affiliations
Clinical Trial

Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial

Hyun Cheol Chung et al. J Immunother Cancer. .

Abstract

Background: We evaluated the antitumor activity and safety of avelumab, a human anti-PD-L1 IgG1 antibody, as first-line switch-maintenance (1 L-mn) or second-line (2 L) treatment in patients with advanced gastric/gastroesophageal cancer (GC/GEJC) previously treated with chemotherapy.

Methods: In a phase 1b expansion cohort, patients without (1 L-mn) or with (2 L) disease progression following first-line chemotherapy for advanced GC/GEJC received avelumab 10 mg/kg intravenously every 2 weeks. Endpoints included best overall response, progression-free survival (PFS), overall survival (OS), and safety.

Results: Overall, 150 patients were enrolled (1 L-mn, n = 90; 2 L, n = 60) and median follow-up in the 1 L-mn and 2 L subgroups was 36.0 and 33.7 months, respectively. The confirmed objective response rate was 6.7% in both subgroups (95% CI, 2.5-13.9% and 1.8-16.2%, respectively), including complete responses in 2.2% of the 1 L-mn subgroup (n = 2). In the 1 L-mn and 2 L subgroups, median duration of response was 21.4 months (95% CI, 4.0-not estimable) and 3.5 months (95% CI, 2.8-8.3) and disease control rates were 56.7 and 28.3%, respectively. Median PFS in the 1 L-mn and 2 L subgroups was 2.8 months (95% CI, 2.3-4.1) and 1.4 months (95% CI, 1.3-1.5), with 6-month PFS rates of 23.0% (95% CI, 14.7-32.4%) and 7.9% (95% CI, 2.6-17.2%), and median OS was 11.1 months (95% CI, 8.9-13.7) and 6.6 months (95% CI, 5.4-9.4), respectively. In the 1 L-mn subgroup, median OS measured from start of 1 L chemotherapy was 18.7 months (95% CI, 15.4-20.6). Across both subgroups, 20.7% had an infusion-related reaction of any grade. Other common treatment-related adverse events (TRAEs) of any grade included fatigue (10.0%) and nausea (6.7%). Treatment-related serious adverse events occurred in 4.0% of patients. Overall, 8.7% had a grade ≥3 TRAE, including 1 treatment-related death.

Conclusion: Avelumab showed clinical activity and an acceptable safety profile in patients with GC/GEJC.

Trial registration: ClinicalTrials.gov NCT01772004 ; registered 21 January 2013.

Keywords: Adenocarcinoma; Avelumab; Esophagogastric junction; Gastric; Maintenance; Metastatic.

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Conflict of interest statement

Ethics approval and consent to participate

The trial was conducted in accordance with the ethics principles of the Declaration of Helsinki and the International Council for Harmonisation Guidelines on Good Clinical Practice. The protocol was approved by the institutional review board or independent ethics committee of each center. All patients provided written informed consent before enrollment.

Consent for publication

Not applicable.

Competing interests

HCC: consultant/advisory role: Bristol-Myers Squibb, Celltrion Healthcare, Eli Lilly, Merck & Co, Merck KGaA, Quintiles, Taiho Pharmaceutical; speakers bureau: Eli Lilly, Foundation Medicine, Merck KGaA; research grants: Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck & Co, Merck KGaA, Ono Pharmaceutical, Taiho Pharmaceutical.

YKK: consulting or advisory role: Bristol-Myers Squibb, Eli Lilly, Ono Pharmaceutical, Roche; research funding: Bayer, Novartis, Roche, Sanofi.

KWL: research funding: AstraZeneca/MedImmune, Daiichi Sankyo, Five Prime Therapeutics, Green Cross Corp, Macrogenics, Merck KGaA, Merck & Co, Ono Pharmaceutical, Taiho Pharmaceutical.

UK: honoraria: AstraZeneca, Bristol-Myers Squibb, Glycotope GmbH, Merck KGaA, Merck & Co, Novartis, Pfizer, Roche/Genentech; consulting or advisory role: AstraZeneca, Bristol-Myers Squibb, Merck Serono, Merck & Co, Pfizer; speakers bureau: AstraZeneca, Bristol-Myers Squibb, Glycotope GmbH, Merck Serono, MSD Oncology, Novartis; research funding: Pfizer; travel, accommodations, expenses: AstraZeneca, Merck KGaA, Merck & Co.

BM: honoraria: Bristol-Myers Squibb, Merck & Co, Merck KGaA, Novartis, Roche; consulting or advisory role: Bristol-Myers Squibb, Merck & Co, Merck KGaA, Novartis, Roche; travel, accommodations, expenses: Bristol-Myers Squibb, Novartis, Roche.

AM: speakers bureau: Genentech.

RP: honoraria: Bristol-Myers Squibb, Roche/Genentech; consulting or advisory role: AstraZeneca, BioMarin, Clovis Oncology, Karus Therapeutics, Mission Therapeutics, Merck & Co, Novartis, Roche/Genentech, Tesaro, Vertex; speakers bureau: Novartis; research funding: AstraZeneca/MedImmune, Clovis Oncology, Eisai, Etherapeutics, Ipsen, Vertex; patents, royalties, other intellectual property: named on patent for use of PARP inhibitor (rucaparib); travel, accommodations, expenses: Merck & Co, Roche/Genentech.

ABG: employment: EMD Serono Inc. (a business of Merck KGaA, Darmstadt, Germany) when the study was performed; stock ownership: Halozyme Therapeutics.

HX: employment: EMD Serono Inc. (a business of Merck KGaA, Darmstadt, Germany).

JH: employment: EMD Serono Inc. (a business of Merck KGaA, Darmstadt, Germany).

VC: employment: EMD Serono Inc. (a business of Merck KGaA, Darmstadt, Germany) when the study was performed; current employment at AstraZeneca; stock and other ownership interests: Bristol-Myers Squibb.

HTA, JL, SYR, DYO, LW, JRI, SSL, MK, DS, and HS declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Change in sum of target lesion diameters over time with avelumab in evaluable patients. a First-line switch-maintenance subgroup (n = 81). b Second-line subgroup (n = 52). Color coding is based on best overall response per Response Evaluation Criteria in Solid Tumors version 1.1. Dotted lines indicate the 3-month timepoint and changes in target lesion size of −30, 0, and +20%
Fig. 2
Fig. 2
Kaplan–Meier estimates of progression-free survival (PFS) and overall survival (OS). a PFS from start of avelumab in the first-line switch-maintenance (1 L-mn) subgroup (n = 90). b OS from start of avelumab in the 1 L-mn subgroup (n = 90). c OS from start of 1 L chemotherapy in the 1 L-mn subgroup (n = 90). d PFS in the second-line (2 L) subgroup (n = 60). e OS in the 2 L subgroup (n = 60)
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