1291P Hypersensitivity reactions (HR) to selpercatinib in RET fusion+ non-small cell lung cancer (NSCLC) patients (pts) following immune checkpoint inhibition (CPI)

Abstract

Background: Selpercatinib (LOXO-292), a highly selective and potent RET kinase inhibitor, demonstrated marked and durable antitumor activity in pts with RET fusion+ NSCLC in an ongoing phase 1/2 trial. We evaluated best responses to last prior therapy received before enrollment and to selpercatinib by last prior therapy subgroups.Methods: Pts with RET fusion+ NSCLC enrolled in the global, multicenter, LIBRETTO-001 trial (NCT03157128) received the recommended phase 2 selpercatinib dose (160 mg twice daily) after dose escalation. This analysis assessed outcomes by category of last systemic therapy received prior to enrollment. Efficacy was analyzed in the first 105 consecutively enrolled pts pretreated with platinum chemotherapy (primary analysis set [PAS]). Adverse events (AEs) were measured in all pretreated pts who received selpercatinib by data cutoff date of 16-Dec-2019. abstracts Annals of Oncology Volume 31 -Issue S4 -2020 S835

Severe Immune Checkpoint Inhibitor Hepatitis in KRAS G12C-Mutant NSCLC Potentially Triggered by Sotorasib: Case Report

“…Nevertheless, our case confirmed CPI-mediated, immune-related hepatitis consistent with the hypothesis that in some CPI-exposed patients, sotorasib may induce a proinflammatory state sufficient to trigger immune-related hepatitis. This is consistent with emerging evidence for CPI-mediated, immune-related AEs requiring a priming event, with established triggers including small molecule drugs osimertinib 3 and selpercatinib 4 and cytomegalovirus reactivation. 5 We therefore identify for the first time that sotorasib may trigger CPI-mediated, immune-related hepatitis in an anti–programmed cell death protein-1 immunotherapy exposed patient.…”

Hallmarks of RET and Co-occuring Genomic Alterations in RET-aberrant Cancers

“…It is defined as a constellation of events in the initial treatment weeks: maculopapular rash, often preceded by fever, with associated arthralgias or myalgias followed by thrombocytopenia and/or AST/ALT increase (common) and/or blood pressure decrease, tachycardia, and/or creatinine increase (less common). About 11% (17/152) in previously treated patients with ICI and 3% (5/177) in ICI-na€ ve patients were found to have treatment-related hypersensitivity reactions, with most patients being successfully treated with dose modification and concomitant steroids (44).…”

Hypersensitivity Reactions to Selpercatinib Treatment With or Without Prior Immune Checkpoint Inhibitor Therapy in Patients With NSCLC in LIBRETTO-001

“…7 Of the 30 cases reported in the overall population, the proportion of patients who experienced a hypersensitivity reaction was highest among patients with RET fusion-positive NSCLC (25 of 329 patients, 8%). 9 Published reports of immune-related reactions to kinase inhibitors in patients previously treated with immune checkpoint inhibitor (ICI) therapy suggest that immunotherapy may increase the risk for and the severity of immune-mediated hypersensitivity reactions with subsequent kinase inhibitor therapy. [10][11][12][13][14][15][16] A detailed characterization of drug-associated hypersensitivity in the global, multicenter, prospective LIBRETTO-001 trial and the conditioning effect of prior ICI therapy have not been reported.…”