Patients are only eligible after signing the informed consent form and must meet all of the
following criteria to be eligible the Medical Access Program.

Inclusion Criteria:

- Patients must be ≥18 years of age (follow local regulatory requirements if the legal
age of consent for participation is >18 years old).

- Patient has histologically or cytologically documented advanced or metastatic NSCLC
with documented non-squamous histology that is not amenable to curative surgery or
radiation.

- Patient had disease progression while on/after receiving their most recent treatment
regimen for advanced or metastatic disease.

- Patient has met the following prior therapy requirements:

- Patients without actionable genomic alterations must have received platinum-based
chemotherapy and PD-(L)1 therapy combined or in either sequence.

- Patients with actionable genomic alterations must meet the following prior
therapy requirements for advanced or metastatic NSCLC: at least 1 targeted
therapy and platinum-based chemotherapy either combined or in either sequence.

- Patient has adequate bone marrow reserve and organ function, based on local laboratory
data, in the opinion of the treating physician.

- If the patient is a female and of childbearing potential, a negative urine or serum
pregnancy test must be provided at time of treatment initiation request.

- If the patient (male and female) is of reproductive/childbearing potential, they must
agree to use a highly effective form of contraception or avoid intercourse during the
program and upon completion of this program and for at least 7 months for females and
4 months for males after the last dose of Dato-DXd.

- At the time of entering the program, the patient agrees that if they are:

- A male patient, they must not freeze or donate sperm at any time during this
program and for at least 4 months after the last dose of Dato-DXd. Preservation
of sperm should be considered prior to enrollment in this program.

- A female patient, they must not donate, or retrieve for their own use, ova at any
time during this program and for at least 7 months after the last dose of
Dato-DXd. Preservation of ova should be considered prior to enrollment in this
program.

- Patients must have a life expectancy of >3 months as determined by the treating
physician.

- Patient is willing and able to provide written informed consent indicating that they
understand the purpose of the Medical Access Program and are willing and able to
participate.

Patients who meet any of the following criteria will not be eligible for the Medical Access
Program.

Exclusion Criteria:

- Patient has a history of non-infectious ILD/pneumonitis that required steroids, has
current ILD/pneumonitis, or have suspected ILD/pneumonitis that cannot be ruled out by
imaging at the time of entering the program.

- Patient has clinically severe respiratory compromise (based on your assessment)
resulting from intercurrent pulmonary illnesses including, but not limited to:

- Any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months prior
to program enrollment, severe asthma, severe chronic obstructive pulmonary
disease, moderate to severe restrictive lung disease, or moderate to severe
pleural effusion).

- Any autoimmune, connective tissue or inflammatory disorders with pulmonary
involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis), OR

- Prior complete pneumonectomy.

- Patient has clinically significant unresolved toxicities from previous anticancer
therapy, defined as toxicities (other than alopecia) not yet resolved to National
Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version
5.0, Grade >1 at start of treatment within the program. Patients with chronic Grade 2
toxicities may be eligible at the discretion of the treating physician after
consultation with the Sponsor Medical Approvers or designees within this program.

- Patient has active or uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV)
infection.

- Patient has active Hepatitis C. (Active Hepatitis C is defined by a positive Hep C Ab
result, quantitative HCV RNA results greater than the lower limits of detection of the
assay, and an ALT or AST greater or equal 2 times the upper limit of normal.)

- Patient has uncontrolled Hepatitis B. (Patients with Hepatitis B [positive HBs antigen
test] must meet the following criteria to be eligible: have an HBV-DNA Viral Load
<2000 IU/mL off treatment or have an HBV-DNA Viral Load <2000 IU/mL on oral antiviral
therapy for at least 4 weeks and during the participation in the study.)

- Patient has known human immunodeficiency virus (HIV) infection that is not well
controlled. All of the following criteria are required to define an HIV infection that
is well controlled:

- Undetectable viral RNA.

- CD4+ count ≥350.

- No history of acquired immune deficiency syndrome-defining opportunistic
infection within the past 12 months, and stable for at least 4 weeks on the same
anti-HIV medications (meaning there are no expected further changes in that time
to the number or type of antiretroviral drugs in the regimen).

- If an HIV infection meets the above criteria, monitoring of viral RNA load and
CD4+ count is recommended.

- Patient has a history of severe hypersensitivity reactions to either the drug or
inactive ingredients (including but not limited to polysorbate 80) of Dato-DXd.

- Patient has a history of severe hypersensitivity reactions to other monoclonal
antibodies.

- Female patients cannot be pregnant or breastfeeding, or intend to become pregnant.

- Patient has prior or ongoing clinically relevant illness, medical condition, surgical
history, physical finding, or laboratory abnormality that, in the treating physician's
opinion, could affect the safety of the patient if prescribed Dato-DXd.

- Patient has clinically significant corneal disease.

- Patient is currently participating in or is in active follow up (as defined by the
protocol) for a fam-trastuzumab deruxtecan-nxki (in the United States [US]) or
trastuzumab deruxtecan (ex US) or Dato-DXd clinical study.

- Patient is eligible for any available oncology clinical trial.

- Patient has received a prior TopoI inhibitor.

- Patient has received prior radiotherapy to the brain within 2 weeks of start of
Dato-DXd treatment or received radiotherapy to the chest within 4 weeks of start of
Dato-DXd treatment, or the patient has experienced radiation-related toxicities
requiring corticosteroids.