Re-sensitization to pembrolizumab following PSMA-CD3 T-cell redirection therapy with JNJ-081 in a patient with mismatch repair-deficient metastatic castration-resistant prostate cancer: a case report

Checkpoint inhibitor therapy has completely changed the way some solid tumors are treated, but it hasn’t shown much success in metastatic castration-resistant prostate cancers ( mCRPC ). A small( 3 & ndash, 5 %) but clinically distinct subset of mCRPC tumors develops a hypermutation phenotype with an elevated tumor mutational burden and high microsatellite instability ( MSI – H )( dMMR ). In prostate tumors, dMMR / MSI – H status has been demonstrated to be a predictive biomarker for response to pembrolizumab. In this report, we describe the case of a patient with mCRPC who had somatic dMMR and had taken pembrolizumab following an initial response. He signed up for a clinical trial with JNJ – 081, an antigen-CD3 bispecific T-cell engager antibody for the prostate, and he only partially responded due to cytokine release syndrome. His prostate-specific antigen decreased from a high of 20.01 to undetectable after 6 weeks and continued to be undiscernible for & gt, 11 months after being reinitiated on pembrolizumab during progression. This is the first instance of bispecific T-cell engager-mediated re-sensitization to checkpoint inhibitor therapy in any cancer that has been reported to our knowledge.

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Categorized as Oncology

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