Second Line Gemcitabine and Nivolumab in Treating Participants With Metastatic Small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. To compare response rate (RR) of gemcitabine and nivolumab (G+N) after 4 cycles (8 weeks)
to historical controls treated with nivolumab alone.

SECONDARY OBJECTIVES:

I. To compare median overall survival (OS) of G+N to historical controls treated with
nivolumab alone.

II. To compare median progression-free survival (PFS) of G+N to historical controls treated
with nivolumab alone.

III. To evaluate for tolerability of G+N at each treatment cycle and then every 8 weeks after
treatment is completed.

EXPLORATORY OBJECTIVES:

I. To correlate immunophenotypic changes among lymphocytes (quantitative measurements of CD4
and CD8 T-cells) with radiographic response and overall survival before treatment, after
treatment and between 8-12 weeks after treatment.

II. Among those patients with tumor mutation burden (TMB) status available, to describe the
association between TMB (low, medium, or high) and RR, OS, and PFS.

III. Assess the patient perspective of symptomatic adverse events using self-reported items
from the National Cancer Institute (NCI) Patient Reported Outcomes-Common Terminology
Criteria for Adverse Events (PRO-CTCAE).

OUTLINE:

Participants receive gemcitabine intravenously (IV) over 30 minutes and nivolumab IV over 60
minutes on day 1. Treatment repeats every 2 weeks for up to 4 courses in the absence of
disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 30 days, 6-10 weeks, and
every 8 weeks thereafter.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed incurable SCLC and have
had prior treatment with platinum-based chemotherapy.

- Patients should not be demonstrating end-organ damage due to rapid progression of
disease based on the most recent assessment of the treating physician.

- Patients must have radiographically measurable metastatic disease by Response
Evaluation Criteria in Solid Tumors (RECIST) criteria.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

- Absolute neutrophil count >= 1,500/mcL.

- Platelets >= 100,000/mcL.

- Chemotherapy agents are known to be teratogenic, therefore women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier method
of birth control) prior to study entry and for the duration of study participation.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately.

- Ability to understand and the willingness to sign an Institutional Review Board
(IRB)-approved informed consent document.

Exclusion Criteria:

- Previously received gemcitabine or nivolumab. Patients who have previously received
other types of immune checkpoint inhibitors (besides nivolumab) can be enrolled.

- Emergent need for palliative radiation.

- Patients may not be receiving any other investigational agents for the treatment of
NSCLC.

- History of allergic reaction to gemcitabine.

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant women are excluded from this study because of the potential for teratogenic
or abortifacient effects with chemotherapy. Because there is an unknown but potential
risk for adverse events in nursing infants secondary to treatment of the mother with
chemotherapy, breastfeeding should be discontinued.