Phase 1b DV281 With an Anti-PD-1 Inhibitor in NSCLC

Pre-clinical studies support the proposed dosing schema to be tested and a potential benefit
of the combination of inhaled DV281 with nivolumab for subjects with advanced NSCLC. This
study (DV9-NSC-01) is designed for establishing an immunologically optimal RP2D for inhaled
DV281 in combination with an approved anti-PD-1 inhibitor. This trial, studying the potential
to enhance the efficacy of an approved anti-PD-1 inhibitor in subjects with advanced NSCLC,
addresses an unmet need for NSCLC patients having tumors that do not respond or do not
respond adequately to anti-PD-1 inhibitor monotherapy.

Inclusion Criteria:

- Have documented histologically or cytologically confirmed advanced NSCLC as the
dominant histology.

- If confirmed EGFR or ALK directed testing warrants actionable targeted therapy, must
have confirmed disease progression on targeted therapy or cannot tolerate targeted
therapy.

- Aged 18 years and older on the day of signing informed consent

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2 for Dose
Escalation phase and ECOG PS 0 to 1 for Dose Expansion phase

- Adequate organ function as indicated by laboratory values

- Life expectancy, in the opinion of the investigator, of at least 3 months

Exclusion Criteria

- Condition of the subjects lung anatomy is such that proper delivery of inhaled DV281
to the specific location of intra-thoracic tumor(s) could be compromised

- Any known additional malignancy that is progressing or required active treatment in
the last 3 years

- Current or history of clinically significant non-infectious pneumonitis

- History of clinically severe lung disease, asthma, or chronic obstructive pulmonary
disease (COPD) requiring emergency management and/or hospitalization in the last year

- Received more than 30 Gy of conventional radiation therapy in the thoracic region
within 26 weeks prior to study enrollment

- Is expected to require any other form of anti-cancer therapy while in the trial.
Zoledronic acid or denosumab as supportive care for bone metastases will be allowed if
started prior to study enrollment

- Diagnosis of immunodeficiency or is receiving systemic steroid therapy (>10 mg of
prednisone or equivalent) or any other form of immunosuppressive therapy (including
immune modulators or systemic corticosteroids) that cannot be discontinued safely
within 14 days prior to study enrollment

- Has a medical condition that requires immunosuppression

- Active autoimmune disease requiring systemic treatment in the past 2 years or a
disease that requires immunosuppressive medication including systemic lupus
erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, or
autoimmune thrombocytopenia. Replacement therapy (eg, thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency)
is not considered a form of systemic treatment.

- Known central nervous system metastases, brain metastases, or carcinomatous meningitis