Hypersensitivity Reactions to Selpercatinib Treatment with or Without Prior Immune Checkpoint Inhibitor Therapy in Patients with Non-Small-Cell Lung Cancer in LIBRETTO-001.

Abstract

Introduction: Immune checkpoint inhibitor (ICI) therapy has been shown to increase the risk/severity of immune-mediated adverse events with subsequent kinase inhibitor treatment in oncogenically-driven cancers. We explored the risk for hypersensitivity with selpercatinib, a first-in-class highly selective and potent, CNS-active RET inhibitor, in prior ICI-treated patients with RET fusion-positive non-small-cell lung cancer (NSCLC) compared with their ICI-naïve counterparts.

Methods: Data from patients enrolled by 16-December-2019 in the ongoing phase 1/2 LIBRETTO-001 (NCT03157128) trial were analyzed for hypersensitivity reactions reported using preferred terms hypersensitivity/drug hypersensitivity and defined as a constellation of symptoms/findings characterized by maculopapular rash, often preceded by fever with arthralgias/myalgias, followed by ≥1 of the following signs/symptoms: thrombocytopenia, increased AST/ALT, hypotension, tachycardia, and/or increased creatinine.

Results: Twenty-two of 329 (7%) patients experienced a grade 1-3 hypersensitivity reaction that met the defined constellation of events were attributed to selpercatinib by investigators, and more often in prior ICI-treated (n=17, 77%) than ICI-naïve (n=5, 23%) patients. Nineteen patients with selpercatinib-related hypersensitivity resumed selpercatinib post-hypersensitivity with dose modification/supportive care. Seventeen patients, of whom 14 received prior ICI therapy, were still on treatment at twice-daily doses of 40 mg (n=5), 80 mg (n=4), 120 mg (n=4), and 160 mg (n=4).

Conclusions: Rates of selpercatinib-related hypersensitivity were low overall and as with other kinase inhibitors, occurred predominantly in prior ICI-treated patients. Hypersensitivity to selpercatinib can be managed with supportive care measures regardless of prior ICI status and are reversible.