Avelumab in Combination Regimens for Relapsed/Refractory DLBCL: Results from the Phase Ib JAVELIN DLBCL Study

• Published in: Targeted oncology Vol. 16; no. 6; pp. 761 - 771
• Main Authors: Hawkes, Eliza A., Phillips, Tycel, Budde, Lihua Elizabeth, Santoro, Armando, Saba, Nakhle S., Roncolato, Fernando, Gregory, Gareth P., Verhoef, Gregor, Offner, Fritz, Quero, Cristina, Radford, John, Giannopoulos, Krzysztof, Stevens, Don, Thall, Aron, Huang, Bo, Laird, A. Douglas, Sandner, Robin, Ansell, Stephen M.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.11.2021; Springer Nature B.V
• Subjects: Adult; Antibodies; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomedicine; Chemotherapy; Herpes Zoster; Humans; Immunoglobulins; Immunotherapy; Investigations; Ligands; Lymphoma; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Non-Hodgkin; Medicine; Medicine & Public Health; Monoclonal antibodies; NCT; NCT02951156; Oncology; Original; Original Research Article; Rituximab; Stem cells; Targeted cancer therapy; Tumors
• ISSN: 1776-2596; 1776-260X
• DOI: 10.1007/s11523-021-00849-8

Background Relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is associated with a poor prognosis despite the availability of multiple treatment options. Preliminary evidence suggests that DLBCL may be responsive to programmed death ligand 1 (PD-L1)/programmed death 1 inhibitors. Objective The JAVELIN DLBCL study was conducted to assess whether a combination of agents could augment and sustain the antitumor immunity of avelumab, an anti-PD-L1 antibody, in R/R DLBCL. Methods This was a multicenter, randomized, open-label, parallel-arm study with a phase Ib and a phase III component. Reported here are the results from the phase Ib study, wherein 29 adult patients with DLBCL were randomized 1:1:1 to receive avelumab in combination with utomilumab (an immunoglobulin G2 4-1BB agonist) and rituximab (arm A), avelumab in combination with utomilumab and azacitidine (arm B), or avelumab in combination with bendamustine and rituximab (arm C). The primary endpoints were dose-limiting toxicities and objective response as assessed by the investigator per Lugano Response Classification criteria. Results Of the seven patients in arm A, one (14.3%) experienced two grade 3 dose-limiting toxicities (herpes zoster and ophthalmic herpes zoster); no dose-limiting toxicities were reported in arms B or C. No new safety concerns emerged for avelumab. One partial response was reported in arm A, three complete responses in arm C, and no responses in arm B. Given the insufficient antitumor activity in arms A and B and the infeasibility of expanding arm C, the study was discontinued before initiation of the phase III component. Conclusions The low level of clinical activity suggests that PD-L1 inhibitor activity may be limited in R/R DLBCL. ClinicalTrials.gov Identifier NCT02951156.