A Study of Daratumumab in Combination With Atezolizumab Compared With Atezolizumab Alone in Participants With Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer

This randomized (study medication assigned to participants by chance), multicenter study will
provide study treatment (atezolizumab alone or atezolizumab+daratumumab) to participants with
previously treated advanced or metastatic NSCLC to assess the anti-tumor activity and safety.
Participants who receive atezolizumab treatment with confirmed disease progression based on
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be eligible to crossover to
treatment (atezolizumab + daratumumab) if they meet crossover eligibility criteria. It is
expected that 100 participants will enroll in the study including 6 participants in the
safety run in phase. Data Monitoring Committee (DMC) will review ongoing data, and may
formulate recommendations on study conduct, including expansion of enrollment of some PD-L1
subgroups, resulting in greater than 96 participants. The participants in the safety run in
phase will be administered the combination of daratumumab and atezolizumab to determine the
safety and tolerability that will be evaluated by the Safety Evaluation Team (SET) for dose
limiting toxicity before the random assignment of participants in a 1:1 ratio in 2 treatment
arms. The study consists of 3 phases: Screening Phase (up to 28 days), Treatment Phase and
Post-Treatment Follow-up Phase which will continue until death, lost to follow-up, withdrawal
of consent, or the End of the Study [the study end is approximately 6 to 12 months after that
last participant is enrolled]. Participants will undergo tumor assessments (RECIST 1.1),
immunogenicity, pharmacokinetics, biomarkers and safety evaluations (adverse events,
laboratory tests, electrocardiogram [ECGs], vital sign measurements, physical examinations,
Eastern Cooperative Oncology Group [ECOG] performance status score) over the time.

Inclusion Criteria:

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

- Have histologically or cytologically confirmed advanced or metastatic non-small cell
lung cancer (NSCLC) (Stage IIIb or greater)

- Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1

- Tumor cell programmed death-ligand 1 (PD-L1) score of tumor cells (TC)1-3 and immune
cell PD-L1 score of tumor-infiltrating immune cells (IC)0-3 as determined by an
immunohistochemistry (IHC) assay performed by the central laboratory on tissue
obtained after the last line of therapy

- A woman of childbearing potential must have a negative highly sensitive serum
(beta-human chorionic gonadotropin [beta- hCG]) at Screening within 14 days prior to
study drug administration

Inclusion Criteria for Crossover:

- Participants must have been randomized to Arm A of the study and had radiographic
disease progression according to RECIST 1.1

- Participants must have a mandatory biopsy at the time of disease progression according
to RECIST 1.1 prior to crossing over. If not clinically feasible, discussion with
Sponsor is required

- The first dose of atezolizumab in the crossover arm should be within 42 days of last
dose but no less than 21 days from the last dose prior to crossing over

Exclusion Criteria:

- Received any of the following prescribed medications or therapies in the past:

1. Anti-cluster of differentiation(CD)38 therapy, including daratumumab

2. CD137 agonists, immune checkpoint inhibitors including but not limited to CTLA-4,
anti-PD-1, and anti-PD-L1 therapies

- Known to be seropositive for human immunodeficiency virus (HIV)

- Prior allogeneic bone marrow transplantation or solid organ transplant

- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins

- Active hepatitis B, defined by a positive test for hepatitis B surface antigen [HBsAg]
or prior history of hepatitis B, defined by presence of antibodies to hepatitis B core
antigen [anti-HBc], regardless of hepatitis B surface antibody [anti-HBs] status;
active hepatitis C or prior history of hepatitis C (anti-HCV positive), except in the
setting of a sustained virologic response (SVR), defined as aviremia 12 weeks after
completion of antiviral therapy. If hepatitis C virus (HCV) antibodies are detected,
an HCV RNA test for viral load by polymerase chain reaction (PCR) should be performed
at least 12 weeks after completion of antiviral therapy to rule out active infection

Exclusion Criteria for Crossover:

- Received any subsequent anti-cancer therapies from the time between the last dose of
atezolizumab prior to the first administration of study drug after crossing over

- Whole brain radiation within 28 days or other radiotherapy within 14 days prior to
first administration of study drug after crossing over