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. 2017 Jul 1;28(7):1658-1666.
doi: 10.1093/annonc/mdx170.

Avelumab: clinical trial innovation and collaboration to advance anti-PD-L1 immunotherapy

K Chin  1 , V K Chand  1 , D S A Nuyten  2
Affiliations

Avelumab: clinical trial innovation and collaboration to advance anti-PD-L1 immunotherapy

K Chin et al. Ann Oncol. .
No abstract available

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Figures

Figure 1.
Figure 1.
Avelumab timeline from discovery to Merck–Pfizer Alliance, breakthrough status, and phase 3 development. BLA, Biologics License Application; BTD, breakthrough therapy designation; FDA, US Food and Drug Administration; MCC, Merkel cell carcinoma; NCI, US National Cancer Institute.
Figure 2.
Figure 2.
Avelumab’s dual mechanism of action. Avelumab is a human IgG1 monoclonal antibody that specifically binds to PD-L1, preventing the interaction between PD-L1 and the inhibitory T-cell receptor, PD-1. PD-L1 blockade removes the suppression of T-cell activity, resulting in T-cell-mediated, adaptive antitumour immune responses. In addition, avelumab has a wild-type IgG1 Fc region that may enable NK cell-mediated ADCC. Avelumab therefore has the potential to utilise both adaptive and innate immune mechanisms to destroy cancer cells. ADCC, antibody-dependent cell-mediated cytotoxicity; Fc, crystallisable fragment; IgG1, immunoglobulin G1; MHC, major histocompatibility complex; NK, natural killer; PD-1, programmed death-1; PD-L1, programmed death ligand-1; TCR, T-cell receptor.
Figure 3.
Figure 3.
Study design for JAVELIN Solid Tumor: an international, phase 1, multicohort dose-escalation and dose-expansion trial (number of patients enrolled as of December 2016 is shown). The dose-escalation part tested four dose levels of avelumab administered as a 1-hour intravenous infusion Q2W using a standard 3 + 3 design. The 10-mg/kg dose level was selected for the dose-expansion part. The four primary dose-expansion cohorts enrolled patients with 2L NSCLC (post-platinum doublet), 1L NSCLC (previously untreated metastatic or recurrent), gastric or GEJ adenocarcinoma (previously treated with chemotherapy with or without progression for 1L Mn or 2L treatment), and metastatic breast cancer (refractory to or progressive after standard-of-care therapy). Efficacy cohorts comprise patients with urothelial carcinoma (progressed after ?1 line of platinum-based therapy or platinum ineligible), R/M SCCHN (progressed after ?1 line of platinum-based therapy or platinum ineligible), gastric or GEJ adenocarcinoma (progressing after treatment with a 1L chemotherapy combination and a 2L ramucirumab regimen), and ovarian cancer (platinum resistant and previously treated with liposomal doxorubicin). Eligible patients for the eight secondary cohorts and additional details for the primary and efficacy cohorts are listed in Table 1. 1L, first line; 2L, second line; 3L, third line; GEJ, gastro-oesophageal junction; Mn, maintenance; NSCLC, non-small-cell lung cancer; Q2W, every 2 weeks; R/M, recurrent/metastatic, SCCHN, squamous cell carcinoma of the head and neck.
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