JNJ-61186372 (JNJ-372), an EGFR-cMET bispecific antibody, in advanced non-small cell lung cancer (NSCLC): An update on phase I results (2018)

Background: JNJ-372 has demonstrated activity in EGFR and cMET-driven tumor models. In an ongoing phase 1 study of JNJ-372 in patients (pts) with advanced NSCLC, 1050 mg 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 4W for 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 age was 63y, 40% were male, 96% were Asian, and median prior systemic therapies was 2. The most 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 were mostly 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 ≥350 mg, with faster clearance PK at the 140-mg dose. Of the 30 response-evaluable pts with EGFRmut disease, treated at doses ≥700 mg, 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 sum of 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. Clinical trial identification: NCT02609776 First posted: November 20, 2015. Editorial acknowledgement: Writing support was provided by Tracy T. Cao, PhD of Janssen Global Services, LLC. and funded by Janssen Global Services, LLC. Legal entity responsible for the study: Janssen Research & Development. Funding: Janssen Research & Development. Disclosure: B.C. Cho: Research funding: Janssen, Novartis, AstraZeneca, Yuhan, Champions Oncology, Abbvie, Dong-A ST, Ono, MOGAM; Honoraria: AstraZeneca, Novartis, MSD, Ono, Roche; Consulting or Advisory role: Janssen, AstraZeneca, Novartis, MSD, Roche, Yuhan; Speakers’ bureau: Novartis J-Y. Han: Research funding: Roche. E. Haura: Research funding: Lilly, Novartis, Boehringer Ingelheim, Janssen, Ignyta, Forma Therapeutics; Consulting or Advisory role: Janssen; Patent: Patent pending on PLA technology related to kinase inhibitor sensitivity biomarkers; Travel/Accommodations: Bristol-Myers Squibb, Roche. J. Bauml: Research funding: Merck, Novartis, Carevive Systems, Janssen, Bayer; Consulting or Advisory Role: Clovis, Bristol-Myers Squibb, Celgene, Boehringer-Ingelheim, AstraZeneca, Genentech, Guardant Health. R.E. Sanborn: Research funding: Merck (investigator-initiated study), Bristol-Myers Squibb (institutional research support), MedImmune (institutional research support); Honoraria: AstraZeneca; Consulting or Advisory Role: AstraZeneca, Seattle Genetics, Takeda, Genentech, Abbvie, Celldex; Travel/Accommodations: Janssen. M. Curtis, E. Attiyeh, N. Haddish-Berhane, K. Bae, R. Knoblauch, L. Sherman, M.V. Lorenzi: Employment: Janssen Stock: Johnson & Johnson. All other authors have declared no conflicts of interest.