Patient case: 60-year-old female with gastric cancer; genetic feature: EGFR

Clinical trial: A Dose Escalation Study of JNJ-61186372 in Participants With Advanced Non-Small Cell Lung Cancer

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

Detailed description: This open label (all participants know the identity of the study drug), multicenter (more than one study site), 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 the recommended phase 2 dose (RP2D). In Part 2, participants with documented epidermal growth factor receptor (EGFR) mutations and measurable disease, whose disease has progressed during 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). Participants' safety will be monitored throughout the study.

Eligibility: Inclusion Criteria:
  -  Participant must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) that is metastatic or unresectable. Participants must have either progressed on prior therapy, or be ineligible for, or have refused all other currently available therapeutic options
  -  For Part 2 only: Participants must also have a documented epidermal growth factor receptor (EGFR) mutation (including primary mutations such as exon 19 deletion, L858R or acquired mutation T790M, or other mutations considered to be activating)
  -  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 progressed during treatment with a marketed EGFR inhibitor
  -  Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  Exclusion Criteria:
  -  Participant has uncontrolled inter-current illness, including but not limited to poorly controlled hypertension, other cardiovascular disease, or diabetes, ongoing or active infection, or psychiatric illness/social situation that would limit compliance with study requirements or confound study results
  -  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 agents with long half-lives, the maximum required time since last dose is 4 weeks. Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less, except for alopecia and peripheral neuropathy
  -  Participants with untreated brain metastases. Participants with treated metastases that are stable based upon central nervous system (CNS) imaging and who are off corticosteroid treatment 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 minimal risk of recurrence)
  -  Participant has not fully recovered from major surgery or significant traumatic injury prior the first dose of study drug or expects to have major surgery during the study period or within 6 months after the last dose of study drug

Relevance to patient case: not relevant