An Efficacy and Safety Study of JNJ-64041757, a Live Attenuated Listeria Monocytogenes Immunotherapy, in Combination With Nivolumab Versus Nivolumab Monotherapy in Participants With Advanced Adenocarcinoma of the Lung

This study evaluates safety and efficacy of JNJ-64041757 with nivolumab. The total study
duration will be up to 3 years. It will consist of safety run-in and randomized phase which
will comprise of Screening phase(Day(D) -28 to D -1),Treatment Phase,End of Adverse Event
Evaluation Period (100 D after last dose of nivolumab)and Post-treatment Follow-up
Phase(Every 3 Months). The primary hypothesis is that addition of JNJ-640417577 to nivolumab
will result in higher objective response rate compared with nivolumab monotherapy in at least
one of programmed death receptor ligand 1 subgroups in participants with relapsed or
refractory StageIIIB or StageIV adenocarcinoma of lung. The study procedures include blood
culture bacterial shedding assessments, pharmacokinetics, immunogenicity, and biomarkers.
Safety will be monitored throughout study.

Inclusion Criteria:

- Disease-related criteria: Histologically documented adenocarcinoma of the lung; Stage
IIIB or Stage IV disease; Biopsy material available for central assessment of
programmed death receptor ligand 1 (PD-L1) and mesothelin

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Progressive disease during or after platinum-based doublet chemotherapy

- A woman of childbearing potential must have a negative serum or urine pregnancy test
within 14 days before the first dose of nivolumab

- Willing and able to adhere to the prohibitions and restrictions specified in this
protocol

Exclusion Criteria:

- Tumor with activating epidermal growth factor receptor (EGFR) mutation or ALK
translocation

- More than 1 prior line of chemotherapy for metastatic disease (Phase 2)

- History of disallowed therapies, as follows: In Phase 1b only: Prior exposure to
anti-programmed death receptor-1(PD1), anti programmed death receptor ligand 1
(PD-L1), anti-programmed death receptor ligand 2 (PD-L2), anti-CD137, or
anti-cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody within 28 days
before the first dose of study agent, In Phase 2 only: Prior exposure to anti-PD1,
anti PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte associated antigen
4 (CTLA-4) antibody, History of listeriosis or vaccination with a Listeria-based
vaccine or prophylactic vaccine within 28 days before the first dose of study agent,
Chemotherapy within 28 days before the first dose of study agent, Radiation within 14
days before the first dose of study agent

- History of any other condition that may require the initiation of anti-tumor necrosis
factor alpha (TNF alpha) therapies or other immunosuppressant medications during the
study

- Active second malignancy within 2 years prior to Cycle 1 Day 1 (Phase 1b) or
randomization (Phase 2)