JNJ-61186372 (JNJ-372), an EGFR-cMET bispecific antibody, in advanced non-small cell lung cancer (NSCLC): An update on phase I results

Abstract

Background: JNJ-372 has demonstrated activity in EGFR and cMET-driven tumormodels. In an ongoing phase 1 study of JNJ-372 in patients (pts) with advancedNSCLC, 1050mg was identified as a recommended phase 2 dose in dose escalation (Part 1) and is being explored in the dose expansion of pts with EGFR-mutated (mut)NSCLC(Part 2). Methods: Pts were treated with JNJ-372 IV weekly x 4Wfor cycle 1, then biweekly thereafter. Pharmacokinetic (PK) sampling was taken at multiple time points for all pts in Part 1 and for the first 6 pts in Part 2. Disease evaluations were performed every 8 weeks. Tumors were characterized at baseline through next-generation sequencing of ctDNA and/or tumor tissue. Results: As of April 13th, 2018, 55 pts received JNJ-372 in Part 1 (n=30) or Part 2 (n=25), with 21 pts (38%) continuing therapy. Median agewas 63y, 40%weremale, 96% were Asian, andmedian prior systemic therapies was 2. Themost frequent (≥15%) adverse events (AEs) were infusion-related reaction (56%), rash/acneiform dermatitis (53%), dyspnea (20%), paronychia (24%), nausea (22%), constipation (18%), stomatitis (18%), decreased appetite (18%), pruritus (16%), fatigue (16%), and peripheral edema (16%). AEs weremostly grade 1-2, with 3 ≥grade 3 treatment-related AEs (myalgia, neutropenia, and peripheral edema, all grade 3). PK was linear and dose proportional at doses ≥350mg, with faster clearance PK at the 140-mg dose. Of the 30 response-evaluable pts with EGFRmut disease, treated at doses ≥700mg, there are 8 partial responses (PRs; 4 confirmed PRs). This includes 6 pts with L858R or Exon19del primary mutations, and acquired resistance to first and/or third-generation EGFR tyrosine kinase inhibitors (TKIs), and 2 pts with primary Exon20ins disease. Activity was also observed in 2 pts with EGFRwt disease (squamous cell carcinoma and pleomorphic adenocarcinoma), each with -20%change in sumof largest diameter. The longest duration of treatment was 13.6 months. Conclusions: JNJ-372 is a novel EGFR-cMET bispecific antibody with a manageable safety profile consistent with EGFR and cMET inhibition. Preliminary evidence suggests JNJ-372 can have activity in EGFR-driven NSCLC, including pts resistant to EGFR TKIs.