Abstract CT111: Avelumab (anti-PD-L1) as first-line maintenance (1L mn) or second-line (2L) therapy in patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC): updated phase Ib results from the JAVELIN Solid Tumor trial
Authors: Chung Hyun Cheol , Arkenau Hendrik-Tobias , Lee Jeeyun , Rha Sun Young , Oh Do-Youn , Wyrwicz Lucjan , Kang Yoon-Koo , Lee Keun-Wook , Bauer Todd M. , Lee Sung Sook , Kemeny Margaret , Keilholz Ulrich , Melichar Bohuslav , Mita Alain , Plummer Ruth , Smith Denis , Gelb Arnold B. , Xiong Huiling , Hong Janet , Chand Vikram , Safran Howard 
Published: August 2018

Abstract
Background: Patients (pts) with advanced GC/GEJC have a poor prognosis and standard chemotherapy options provide limited efficacy with significant toxicity. Avelumab, a human anti–PD-L1 IgG1 monoclonal antibody, has shown durable efficacy and acceptable safety in various tumor types. Here, we report updated data from JAVELIN Solid Tumor (NCT01772004) for avelumab treatment in pts with previously treated GC/GEJC.
Methods: Pts with advanced GC/GEJC without or with disease progression after first-line combination chemotherapy in the metastatic setting (1L mn and 2L subgroups, respectively) received avelumab 10 mg/kg IV Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Best overall response and progression-free survival (PFS) per RECIST v1.1 and overall survival (OS) were evaluated from the start of avelumab treatment. Time-to-event endpoints were estimated using the Kaplan–Meier method.
Results: As of Sep 30, 2017, pts in the 1L mn subgroup (n=90) and 2L subgroup (n=60) had a median (range) follow-up of 36.0 mo (27–42) and 33.7 mo (25–42), respectively. In the 1L mn subgroup, best response on prior chemotherapy was partial response in 27.8%, stable disease in 65.6%, and not evaluable in 6.7%. Confirmed objective response rate (ORR) during avelumab 1L mn therapy (additional effect after end of chemotherapy) was 6.7% (95% CI 2.5–13.9), including complete response in 2.2%. Median duration of response was 21.4 months (95% CI 4.0–not estimable) and responses to avelumab lasted ≥12 mo in an estimated 50.0% of responders (95% CI 11.1–80.4). In evaluable pts with PD-L1+ (n=26) and PD-L1− (n=51) tumors (≥1% tumor cell cutoff; Dako PD-L1 IHC 73-10 pharmDx assay), ORR was 7.7% (95% CI 0.9–25.1) vs 3.9% (95% CI 0.5–13.5). The disease control rate (DCR) was 56.7% and median PFS was 2.8 mo (95% CI 2.3–4.1); median OS was 11.1 mo (95% CI 8.9–13.7) when measured from the start of avelumab therapy (12-mo rate 46.2%; 95% CI 35.6–56.1), and 18.7 mo (95% CI 15.4–20.6) when measured from start of 1L chemotherapy. In the 2L subgroup, confirmed ORR was 6.7% (95% CI 1.8–16.2), DCR was 28.3%, median PFS was 1.4 mo (95% CI 1.3–1.5), and median OS was 6.8 mo (95% CI 5.4–9.5). Across both subgroups, 56.7% had a treatment-related adverse event (TRAE) of any grade, most commonly (&gt;10%) infusion-related reaction (12.7%) and fatigue (10.0%). 8.7% had a grade ≥3 TRAE, with 1 treatment-related death (hepatic failure/autoimmune hepatitis). 15.3% had an immune-related AE (grade ≥3 in 2.0%).
Conclusion: Avelumab showed promising clinical activity and an acceptable safety profile in pts with advanced GC/GEJC with prior chemotherapy. A phase 3 trial of avelumab as 1L mn therapy vs continuation of 1L chemotherapy in pts with advanced GC/GEJC is ongoing (NCT02625610).
Citation Format: Hyun Cheol Chung, Hendrik-Tobias Arkenau, Jeeyun Lee, Sun Young Rha, Do-Youn Oh, Lucjan Wyrwicz, Yoon-Koo Kang, Keun-Wook Lee, Todd M. Bauer, Sung Sook Lee, Margaret Kemeny, Ulrich Keilholz, Bohuslav Melichar, Alain Mita, Ruth Plummer, Denis Smith, Arnold B. Gelb, Huiling Xiong, Janet Hong, Vikram Chand, Howard Safran. Avelumab (anti-PD-L1) as first-line maintenance (1L mn) or second-line (2L) therapy in patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC): updated phase Ib results from the JAVELIN Solid Tumor trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT111.