NAUTIKA1: A Multicenter, Phase II, Neoadjuvant and Adjuvant Study of Multiple Therapies in Biomarker-Selected Patients with Resectable Stages IB-III Non-Small Cell Lung Cancer

This trial will evaluate the efficacy and safety of various therapies in participants
with Stage IB, IIA, IIB, IIIA, or selected IIIB resectable and untreated NSCLC tumors
that meet protocol-specified biomarker criteria.

Inclusion Criteria for Neoadjuvant Therapy:

- Pathologically documented NSCLC:

- Newly diagnosed early-stage NSCLC stages IB, IIA, IIB, IIIA, or selected IIIB (T3N2
only) NSCLC of squamous or non-squamous histology. Staging should be based on the
8th edition of the American Joint Committee on Cancer (AJCC)/Union Internationale
Contre le Cancer (UICC) NSCLC staging system

- T4 primary NSCLC will be allowed only on the basis of size. Invasion of the
diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve,
esophagus, vertebral body, carina, and separate tumor nodules in a different
ipsilateral lobe is not permitted

- All participants will undergo clinical staging using computed tomography (CT) and
positron emission tomography (PET) scanning, as well as brain imaging using magnetic
resonance imaging (MRI). Invasive mediastinal staging by either mediastinoscopy or
endo-bronchial ultrasonography is highly encouraged for participants with
radiographically suspected mediastinal nodal disease (i.e., N2) but not mandated if
the CT or PET scans showed no evidence of N2 disease

- Molecular testing results from clinical laboratory improvement amendments
(CLIA)-certified laboratories and showing at least one of the following
abnormalities: ALK fusion, ROS1 fusion, NTRK1/2/3 fusion; BRAF V600 mutation, RET
fusion, PD-L1 expression in ≥ 1% tumor cells as determined by Food and Drug
Administration (FDA)-approved test, KRAS G12C mutation

- Measurable disease, as defined by RECIST v1.1

- NSCLC must have a solid or subsolid appearance on CT scan and cannot have a purely
ground glass opacity appearance. For subsolid lesions, the tumor size (i.e.,
clinical T stage) should be measured based on the solid component only, exclusive of
the ground glass opacity component

- Evaluated by the attending surgeon prior to study enrollment to verify that the
primary tumor and any involved lymph nodes are technically completely resectable and
verify that the participant is medically operable

- Adequate pulmonary function to be eligible for surgical resection with curative
intent

- Adequate cardiac function to be eligible for surgical resection with curative intent

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Adequate hematologic and end-organ function

- Negative hepatitis B surface antigen (HBsAg) test at screening for cohort

- Negative total hepatitits B core antibody (HBcAb) test at screening for cohort, or
positive total HBcAb test followed by a negative hepatitis B virus (HBV)
deoxyribonucleic acid (DNA) test at screening

- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV
antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening

- Male participants must be willing to use acceptable methods of contraception

- Female participants of childbearing potential must agree to use acceptable methods
of contraception

Inclusion Criteria for Adjuvant Therapy (TKI Cohorts and KRAS G12C cohort [if continuing
on Divarasib]):

- Participants whose tumors lack radiographic progression

- ECOG Performance Status of 0 or 1

- Adequate hematologic and end-organ function

Exclusion Criteria

- NSCLC that is clinically T4 by virtue of mediastinal organ invasion or Stage IIIB by
virtue of N3 disease

- Any prior therapy for lung cancer, including chemotherapy, targeted therapy,
immunotherapy, or radiotherapy, within 2 years

- Participants with prior lung cancer

- Major surgical procedure within 28 days prior to Cycle 1, Day 1

- Malignancies other than the disease under study within 3 years prior to Cycle 1, Day
1, with the exception of participants with a negligible risk of metastasis or death
and with expected curative outcome

- Treatment with an investigational agent for any condition within 4 weeks prior to
Cycle 1, Day 1

- Participants known to be positive for human immunodeficiency virus (HIV) are
excluded if they meet any of the following criteria: cluster of differentiation 4
(CD4)+ T-cell count of <350 cells/microliters (cells/µL); detectable HIV viral load;
history of an opportunistic infection within the past 12 months; on stable
antiretroviral therapy for <4 weeks

- Severe infection within 4 weeks prior to initiation of study treatment, including
but not limited to hospitalization for complications of infections, or any active
infection that, in the opinion of the investigator, could impact participant safety

- Pregnant or lactating, or intending to become pregnant during the study