Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer

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 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 previous treatment 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 30 days after the last dose of study drug);
and a Follow Up period (approximately 6 months). 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. Participants must have either
progressed after receiving prior therapy for metastatic disease, or be ineligible for,
or have refused all other currently available therapeutic options

- For Part 2 only: Participants must also have disease with a previously diagnosed
activating epidermal growth factor receptor (EGFR) mutation (includes both inhibitor
sensitive primary mutations such as Exon 19 deletion and L858R [Cohort C], as well as
marketed tyrosine kinase inhibitor [TKI] -resistant mutations such as Exon 20
insertion [Cohort C and D]). Documentation of EGFR mutation eligibility by
CLIA-certified laboratory (or equivalent) testing is required

- 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: Cohort A and B: Participants disease must have most recently progressed
following treatment with a marketed EGFR inhibitor. Exception: In participants
diagnosed with mutations associated with de novo EGFR inhibitor resistance (for
example, exon 20 insertions), only previous treatment with combination platinum-based
chemotherapy is required. Cohort C: Participants must have documented EGFR or
mesenchymal-epithelial transition (cMET) alterations mediating resistance to previous
treatment with a third generation TKI (for example, osimertinib), or in the case of
primary Exon 20ins disease, previous treatment with a TKI with known activity against
Exon 20ins disease (for example, poziotinib). Cohort D: Participants must have been
previously diagnosed with an EGFR Exon 20 insertion

- 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

- 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 [any grade], Grade less than or equal to [<=] 2 peripheral
neuropathy, and Grade less than [<] 2 hypothyroidism stable on hormone replacement).
For Part 2 only: Cohorts A and B: 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). Cohort C: Prior treatment
with more than 2 lines of cytotoxic chemotherapy for metastatic disease (maintenance
therapy is not included). Cohort D: Previous treatment with an EGFR TKI with activity
against EGFR Exon 20 insertions (such as poziotinib)

- Participants with untreated brain metastases. Participants with treated metastases
that are clinically stable and asymptomatic for at least 2 weeks 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 3
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)

- 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