TY - JOUR
T1 - Avelumab in Combination Regimens for Relapsed/Refractory DLBCL
T2 - Results from the Phase Ib JAVELIN DLBCL Study
AU - Hawkes, Eliza A.
AU - Phillips, Tycel
AU - Budde, Lihua Elizabeth
AU - Santoro, Armando
AU - Saba, Nakhle S.
AU - Roncolato, Fernando
AU - Gregory, Gareth P.
AU - Verhoef, Gregor
AU - Offner, Fritz
AU - Quero, Cristina
AU - Radford, John
AU - Giannopoulos, Krzysztof
AU - Stevens, Don
AU - Thall, Aron
AU - Huang, Bo
AU - Laird, A. Douglas
AU - Sandner, Robin
AU - Ansell, Stephen M.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
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U2 - 10.1007/s11523-021-00849-8
DO - 10.1007/s11523-021-00849-8
M3 - Article
C2 - 34687398
AN - SCOPUS:85117762478
SN - 1776-2596
VL - 16
SP - 761
EP - 771
JO - Targeted Oncology
JF - Targeted Oncology
IS - 6
ER -