Safety & Immunogenicity of JNJ-64041757, Live-attenuated Double-deleted Listeria Immunotherapy, in Subjects With Non Small Cell Lung Cancer

This is a first-in-human (FIH), Phase 1, open-label, multicenter and 2-part study in
participants with advanced (Stage IIIb) or metastatic (Stage IV) non-small cell lung cancer
(NSCLC) (adenocarcinoma). Part 1 of study will be Dose Escalation phase to determine the
recommended Phase 2 dose (RP2D) based on safety and pharmacodynamic assessments and Part 2
will be Dose Expansion Phase to evaluate 2 expansion cohorts (Cohort 2A and 2B) after the
RP2D for JNJ-64041757 is determined in Part 1. The study will consist of a Screening Period
(from signing of informed consent until immediately before the first dose), an open-label
Treatment Period (from the first dose of study drug until the End-of-Treatment Visit); and a
Post treatment Follow-up Period (after the End-of Treatment Visit until study
discontinuation). Dose limiting toxicity (DLT) in part 1, antigen-specific T-cell response in
part 2 and incidence of adverse events in both the parts will be primarily evaluated.

Inclusion Criteria:

- Disease-related criteria for Part 1 and Part 2: 1) Histologically or cytologically
documented non-small cell lung cancer (NSCLC) - adenocarcinoma; 2) Stage III b or IV
disease; 3) Tested for presence of echinoderm microtubule-associated protein-like 4
anaplastic lymphoma kinase (EML4-ALK) rearrangement; 4) Received at least 2 prior
lines of Food and Drug Administration (FDA)-approved systemic therapy, of which one
therapy has to be a platinum-containing regimen OR failed or completed a first-line
platinum-containing regimen and refused a second-line regimen despite being informed
about the different therapeutic options and their specific clinical benefit by the
investigator; the content of this informed consent discussion including the
therapeutic options reviewed by the investigator needs to be documented and the
subject needs to sign a specific consent form; Disease-related criteria for Cohort 2B
only: 1) Mesothelin protein overexpression, defined by immunohistochemistry (IHC) as
detection of the protein by greater than or equal (>=) 50 percent (%) of tumor cells
on archived tumor material; 2) Primary tumor or metastatic lesion(s) amenable to tumor
core biopsies

- At least 1 measurable tumor lesion per RECIST v1.1 (exception: subjects in Part 1 are
not required to present with measurable disease)

- Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 to 1

- At least 28 days since the last chemotherapy or immunotherapy prior to the first dose;
at least 14 days since the last radiation prior to the first dose (exception:
palliative radiotherapy for pain can be used greater than or equal to (>=) 7 days
prior to or after infusion)

Exclusion Criteria:

- Untreated brain metastases. Subjects must have completed treatment for brain
metastasis, and be neurologically stable off steroids, for at least 28 days prior to
first dose of study drug

- History of listeriosis or vaccination with a listeria-based vaccine or prophylactic
vaccine (eg, influenza, pneumococcal, diphtheria, tetanus, and pertussis [dTP/dTAP])
within 28 days of study treatment

- Known allergy to both penicillin and trimethoprim/sulfamethoxazole. Participants who
are allergic to only one of these antibiotics are allowed to enroll

- Concurrent treatment with anti-Tumor necrosis factor alpha (TNF alpha) therapies,
systemic corticosteroids (prednisone dose greater than [>]10 mg per day or equivalent)
or other immune suppressive drugs within the 2 weeks prior to Screening. Steroids that
are topical, inhaled, nasal (spray) or ophthalmic solution are permitted

- Positive test result for human immunodeficiency virus (HIV) or acquired immune
deficiency syndrome (AIDS)