Inclusion Criteria:

- STEP 1 REGISTRATION

- Patient must be ≥ 70 years of age

- Patient must have histologically or cytologically confirmed non-small cell lung cancer
(NSCLC) with PD-L1 Tumor Proportion Score (TPS) range of 1-49%

- Patient must have Stage IIIB, IIIC or IV disease and not be candidates for combined
chemo-radiation. NOTE: Prior chemo-radiation therapy (RT) for stage III with
recurrence is allowed

- Patient must have a tumor that is negative for EGFR mutation/ALK translocations or
other actionable first line mutations in which patients would receive first-line oral
tyrosine kinase inhibitors

- Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2

- Patient must agree not to father children while on study and for 6 months after the
last dose of protocol treatment

- Patient must have the ability to understand and the willingness to sign a written
informed consent document. Patients with impaired decision-making capacity (IDMC) who
have a legally authorized representative (LAR) or caregiver and/or family member
available will also be considered eligible

- Absolute neutrophil count (ANC) ≥ 1,500/mcL (obtained within 14 days prior to Step 1
registration)

- Platelets ≥ 75,000/mcL (obtained within 14 days prior to Step 1 registration)

- Hemoglobin (Hgb) ≥ 8.0 g/dL (obtained within 14 days prior to Step 1 registration)

- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (obtained within 14
days prior to Step 1 registration)

- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
≤ 3.0 × institutional ULN (obtained within 14 days prior to Step 1 registration)

- Creatinine clearance (CrCL) ≥ 45 mL/min (estimated using Cockcroft-Gault method with
actual body weight or measured) (obtained within 14 days prior to Step 1 registration)

- Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral
therapy with undetectable viral load within 6 months of Step 1 registration are
eligible for this trial

- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated

- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have undetectable HCV viral

- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial

- Patient must be English or Spanish speaking to be eligible for the QOL component of
the study

- NOTE: Sites cannot translate the associated QOL forms

- Patient must not have symptomatic central nervous system disease (CNS) metastases.
Patients with a clinical history of CNS metastases or cord compression are eligible if
they have been definitively treated and are clinically stable for at least 14 days
prior to Step 1 registration and off all steroids for at least 24 hours prior to Step
1 registration. Patients with asymptomatic CNS metastases are eligible

- Patient must not have had any prior cytotoxic chemotherapy regimen for metastatic
disease. Chemotherapy given in the setting of adjuvant therapy or locally advanced
disease is allowed as long as treatment was completed, and they have fully recovered
from treatment related adverse events prior to Step 1 registration

- Patient must not have had any prior immunotherapy for metastatic disease.
Immunotherapy given in the setting of adjuvant therapy or locally advanced disease is
allowed as long as treatment was completed greater than 6 months prior to Step 1
registration

- Patient must not have a history of uncontrolled autoimmune conditions with the
following exceptions, which are allowed: alopecia, vitiligo, rheumatoid arthritis,
psoriasis/psoriatic arthritis, Hashimoto's thyroiditis, lupus, inflammatory bowel
disease

- Patient must not be on immunosuppressive medication, including steroids (if doses
exceed the equivalent of prednisone 10 mg daily). Short courses of steroids which are
discontinued prior to randomization are acceptable. Patients on inhaled, intranasal
and/or topical steroids are eligible

- Investigator must declare their intended chemotherapy regimen should their patient be
randomized to Arm B (doublet vs singlet)

- STEP 2 RANDOMIZATION

- Patient must have completed the baseline Geriatric Assessment (GA) after Step 1
registration and prior to Step 2 randomization

Exclusion Criteria: 

• Less than 70 years of age. 

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 4/1/2024. Questions regarding updates should be directed to the study team contact