Avelumab in relapsed/refractory classical Hodgkin lymphoma: phase 1b results from the JAVELIN Hodgkins trial.

Abstract

The 9p24.1 chromosomal alteration in classical Hodgkin lymphoma (cHL) is associated with increased expression of programmed death ligand 1 (PD-L1)/PD-L2 and an immunosuppressive tumor microenvironment. Blockade of PD-L1/PD-1 interactions with avelumab (anti-PD-L1) is hypothesized to restore antitumor immunity. JAVELIN Hodgkins was a phase 1b, multiple-dose, open-label, randomized, parallel-arm trial of avelumab in patients with relapsed/refractory (R/R) cHL. Primary end points included avelumab target occupancy by dose/schedule in peripheral blood immune cells and pharmacokinetic parameters. Secondary end points included safety and antitumor activity. Four dose levels and 2 dosing schedules were investigated: 70, 350, and 500 mg administered every 2 weeks; 500 mg every 3 weeks; and 10 mg/kg every 2 weeks. Thirty-one patients with R/R cHL were randomized; 9 (29.0%) and 20 (64.5%) had received 3 or ≥4 prior anticancer treatments, respectively. Target occupancy of >90% was observed across all treatment arms, throughout the dosing interval. Avelumab pharmacokinetic data were similar to those previously reported. The most common treatment-related adverse events of any grade were infusion-related reaction (30.0%), nausea (20.0%), increased alanine aminotransferase and rash (16.7% each), and fatigue (13.3%). The objective response rate (ORR) in all randomized patients was 41.9%, with a complete response rate of 19.4%; ORR in those with prior allogeneic hematopoietic stem cell transplant (allo-HSCT) was 55.6%. Due to decreased use of allo-HSCT in patients with R/R cHL, the expansion phase enrolling post-allo-HSCT patients was terminated. Avelumab was tolerable and demonstrated antitumor activity in heavily pretreated patients with cHL, suggesting that PD-L1 blockade may be sufficient for therapeutic benefit in cHL. This trial was registered at www.clinicaltrials.gov as #NCT02603419.

• Authors: Alex F Herrera, Catherine Burton, John Radford, Fiona Miall, William Townsend, Armando Santoro, Pier Luigi Zinzani, David Lewis, Camilla Fowst, Satjit Brar, Bo Huang, Aron Thall, Graham P Collins
• Journal: Blood advances (Blood Adv) Vol. 5 Issue 17 Pg. 3387-3396 (09 14 2021) ISSN: 2473-9537 [Electronic] United States
• PMID: 34477818 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by The American Society of Hematology.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• avelumab

Topics

• Antibodies, Monoclonal (adverse effects)
• Antibodies, Monoclonal, Humanized
• Hodgkin Disease (drug therapy)
• Humans
• Neoplasm Recurrence, Local (drug therapy)
• Tumor Microenvironment