Abstract 3412: Benralizumab for treatment of eosinophil-related cutaneous adverse events associated with checkpoint inhibitors and anticancer targeted therapies: Phase 2 study
Authors: Lacouture Mario E. , Maier Tara , Pan Alexander , Chen Anna , Dranitsaris George , Shah Neil J. , Chandarlapaty Sarat , Dang Chau , Gajria Devika , Gordon Allison , Iyengar Neil , Razavi Pedram , Robson Mark , Rosen Ezra , Wong Serena , Harris Ucalene , Ketosugbo Kwami , Bravo Cindy , Jain Manu , Markova Alina 
Published: March 2024

Background: Eosinophil-related cutaneous adverse events (ercAEs) are common toxicities of PI3K inhibitors, antibody drug conjugates (ADCs), checkpoint inhibitors (CPIs), and targeted cancer therapies. While systemic corticosteroids are effective, their use is limited by additional toxicities and high recurrence. Benralizumab is an anti-IL-5Rα monoclonal antibody that induces eosinophil depletion via antibody-dependent cellular cytotoxicity, and is FDA-approved for severe eosinophilic asthma but has not been studied for ercAEs.

Methods: We conducted a single-center, single-arm, Phase 2 trial (NCT04552288) of benralizumab in cancer patients with Grade 2/3 ercAEs from PI3K inhibitors, ADCs, CPIs or targeted therapies. Patients received benralizumab 30 mg subcutaneously every 4 weeks for 3 doses, then every 8 weeks for 3 doses. The primary endpoint was clinical response, defined as reduction in ercAE Grade to 0/1 at Week 4. Secondary endpoints included changes in quality of life, rash body surface area (BSA), cytokines and eosinophil biomarkers, as well as adverse events (AEs).

Results: Forty-seven patients were enrolled, predominantly with breast (55.3%), bladder (10.6%), melanoma (10.6%), or kidney (6.4%) cancer. Baseline ercAEs were Grade 2 (48.9%) and Grade 3 (51.1%), most often from PI3K inhibitors (46.8%), CPIs (21.3%), tyrosine kinase inhibitors (8.5%) or ADCs (8.5%). Overall, 32 of 42 evaluable patients (76.2%) had clinical response by Week 4, with decreased ercAE grade (mean 2.4 to 0.9, p&lt;0.0001), improved quality of life, reduced rash BSA, decreased peripheral and skin eosinophils (all p&lt;0.0001), and cytokine changes. Clinical response by Week 4 was seen in all patients with ercAEs from alpelisib (PI3K inhibitor; n=18) or enfortumab vedotin (ADC; n=4); p-value for both: p&lt;0.05. Mild-to-moderate mucositis, diarrhea, and xerosis were the most common AEs, all unrelated to benralizumab.

Conclusions: Benralizumab demonstrated favorable safety and efficacy for Grade 2/3 ercAEs from cancer therapies, especially alpelisib and enfortumab vedotin. Larger placebo-controlled trials are warranted to confirm these preliminary findings.

Citation Format: Mario E. Lacouture, Tara Maier, Alexander Pan, Anna Chen, George Dranitsaris, Neil J. Shah, Sarat Chandarlapaty, Chau Dang, Devika Gajria, Allison Gordon, Neil Iyengar, Pedram Razavi, Mark Robson, Ezra Rosen, Serena Wong, Ucalene Harris, Kwami Ketosugbo, Cindy Bravo, Manu Jain, Alina Markova. Benralizumab for treatment of eosinophil-related cutaneous adverse events associated with checkpoint inhibitors and anticancer targeted therapies: Phase 2 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3412.