A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Subjects with Advanced Non-Small Cell Lung Cancer

The purpose of this study is to evaluate the safety and pharmacokinetics, establish one or more recommended phase 2 dose (RP2D) regimens, and to assess the preliminary efficacy of JNJ-61186372 in participants with advanced non-small cell lung cancer (NSCLC).

This open label, multicenter, first-in-human study consists of 2 parts. Part 1 is a dose escalation and Part 2 is a dose expansion cohort. In Part 1, participants with evaluable non-small cell lung cancer (NSCLC) will be enrolled into cohorts at increasing dose levels of JNJ-61186372, which will be administered in 28 day treatment cycles. The dose will be escalated until the maximum tolerated dose (MTD, or maximum administered dose [MAD], if no MTD is found) is reached. Part 1 will follow a traditional 3+3 design. At each dose level, 3 participants will complete Cycle 1. If no dose limiting toxicity (DLT) occurs in these 3 participants, then escalation will continue in a new cohort of 3 participants. Data from Part 1 will be used to determine one or more recommended phase 2 dose (RP2D) regimen(s). In Part 2, participants with documented epidermal growth factor receptor (EGFR) mutations and measurable disease, whose disease has progressed after treatment with a marketed EGFR inhibitor, will be enrolled and receive JNJ-61186372 at the RP2D determined in Part 1. For both parts, the study consists of 3 periods: a Screening period (up to 28 days prior to the first dose of study drug); a Treatment period (first dose of study drug until the last dose of study drug); and a Follow Up period (through 30 days after the last dose). All participants will be followed for survival in the post-treatment follow-up period until the end of study and safety will be monitored throughout the study.

Inclusion Criteria:
• Participant must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) that is metastatic or unresectable.
• For Part 2 only: Participants must also have an activating epidermal growth factor receptor (EGFR) mutation documented at the time of diagnosis.
• For Part 1: Participant must have evaluable disease. For Part 2: Participant must have measurable disease according to Response Criteria in Solid Tumors (RECIST) v1.1
• For Part 2: Participants disease must have most recently progressed following treatment with a marketed EGFR inhibitor. Exception: In subjects diagnosed with mutations associated with de novo EGFR inhibitor resistance, only previous treatment with combination platinum-based chemotherapy is required.
• Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion Criteria:
• Participant has uncontrolled inter-current illness
• Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives whichever is longer, before the first administration of JNJ-61186372. For Part 2 only: Prior treatment with chemotherapy for metastatic disease is not allowed unless the tumor mutation carries de-novo resistance to EGFR tyrosine kinase inhibitor (TKI) (eg, exon 20 insertions)
• Participants with untreated brain metastases. Participants with treated metastases that are stable based upon central nervous system (CNS) imaging and who are off or receiving low-dose corticosteroid treatment (=<10 mg prednisone or equivalent) for at least 2 weeks prior to study treatment are eligible
• Participant has a history of malignancy other than the disease under study within 5 years before Screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with or minimal risk of recurrence within a year from screening).
Phase I
Rachel Sanborn, M.D.
Janssen Research & Development
Brenda Fisher
  • Oncology and Hematology Care Westside
  • Providence Cancer Institute Franz Clinic