A Phase I/II, Open-label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of rilvegostomig (AZD2936) Anti-TIGIT/Anti-PD-1 Bispecific Antibody in Participants with Advanced or Metastatic Non-small Cell Lung Cancer (ARTEMIDE-01)

Disease for part D only:
•Stage IV squamous or non-squamous NSCLC.
•PD-L1 TPS >= 50%
•provision of archival tumor tissue (or fresh tumor tissue biopsy must
be confirmed if archival tumor tissue is not available and if clinically
feasible) is mandatory at screening for all study parts
•No sensitizing EGFR mutations or ALK fusions.
•No documented test result for other known genomic alteration for which a
targeted therapy is approved in first line per local standard of care (ROS1,
NTRK fusions, BRAF, V600E mutation, etc.)

Prior therapy:
•Part D (Dose Expansion): Must meet one of the definitions below:
(i) No prior treatment for NSCLC, and not in need of rapid disease control via
chemotherapy-containing regimen, or
(ii) Prior treatment for NSCLC with one regimen consisting of chemotherapy only.
•No unresolved toxicities of >= Grade 2 (CTCAE v5.0) from prior therapy
(excluding
vitiligo, alopecia, endocrine disorders that are controlled with replacement
hormone
therapy, asymptomatic laboratory abnormalities).

Overall condition:
•ECOG performance status 0 or 1 at enrolment.
•Life expectancy of >= 12 weeks at enrolment.
•Adequate bone marrow, liver and kidney function.

- Participants with either of the following are excluded:
(a) Sensitizing epidermal growth factor receptor mutations or anaplastic
lymphoma kinase fusions (documented test result is mandatory for patients with
non-squamous histology). For patients with squamous histology mutation, testing
is mandatory only
if participant is a never smoker or in the presence of a mixed histology.
(b) Documented test result for any other known genomic alteration for which a
targeted therapy is approved in first line per local standard of care (eg,
ROS1, NTRK fusions, BRAF, V600E mutation, etc).

- part D only:
Any prior systemic treatment with an immune-oncology agent, including but
not limited to anti-PD-1, anti-PD-L1, anti-CTLA-4. Treatment with one previous
systemic chemotherapy will be allowed.

- Symptomatic central nervous system (CNS) metastasis.
(a) Note: Participants with known CNS lesions should be asymptomatic,
adequately treated with stereotactic radiation therapy, craniotomy, gamma knife
therapy, or whole brain radiotherapy, with no subsequent evidence of CNS
progression (documented with magnetic resonance imaging [MRI] scans showing the
absence of brain metastasis progression after radiotherapeutic intervention);
participants must not require steroid exceeding 10 mg prednisone or 2 mg/day of
dexamethasone or equivalent; participants with a history of CNS metastases must
have MRI of the brain at screening. Participants with CNS metastases who are
receiving steroids must be on a stable dose of steroids for >= 7 days prior to
study entry and prior to baseline imaging.

- Thromboembolic event within 3 months before the first dose of investigational
product.

- History of organ transplant.

- Active primary immunodeficiency/active infectious disease(s):
(a) Active infection including tuberculosis (TB) (clinical evaluation that
includes clinical history, physical examination, and radiographic findings and
TB testing in line with local practice).
(b) Human immunodeficiency virus (HIV) (positive for HIV-1 or HIV-2 antibodies).
(c) Chronic or active hepatitis B, chronic or active hepatitis C; however,
participants who have chronic hepatitis B and are receiving suppressive
antiviral therapy are allowed to be enrolled if alanine aminotransferase (ALT)
is normal and viral load is controlled. Controlled hepatitis B viral load is
defined as serum hepatitis B virus DNA < 100 U/mL by polymerase chain reaction
(PCR). Participants with controlled hepatitis B viral load must remain on
antiviral therapy, per institutional practice, during the study treatment and
follow-up period to ensure adequate viral suppression. Participants who have
chronic hepatitis C are allowed to be enrolled if ALT is normal and hepatitis C
virus (HCV) RNA undetectable by PCR, either spontaneously or in response to a
successful prior course of anti-hepatitis C therapy (Regev et al,
2020).Controlled hepatitis C viral load is defined as undetectable hepatitis C
RNA by PCR
either spontaneously or in response to a successful prior course of
anti-hepatitis C therapy.
(d) Acute hepatitis A.
(e) For all participants in the study, all local institutional standards for
coronavirus disease 2019 (COVID-19) must be followed for testing. For
participants with a known previous COVID-19 infection, either negative PCR test
must be documented prior to the first dose or a minimum of 10 days must have
elapsed since the last positive COVID-19 test.

- History of arrhythmia (such as multifocal premature ventricular contractions,
bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires
treatment (National Cancer Institute [NCI] CTCAE v5.0 Grade 3); symptomatic or
uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained
ventricular tachycardia.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or
active known infection, cardiomyopathy of any etiology, symptomatic congestive
heart failure (as defined by New York Heart Association class >= 3), ILD,
uncontrolled hypertension, uncontrolled diabetes mellitus, unstable angina
pectoris, history of myocardial infarction within the past 6 months, serious
chronic gastrointestinal conditions associated with diarrhea (eg, active
inflammatory bowel disease), active non-infectious skin disease
(including any grade rash, urticarial, dermatitis, ulceration, or psoriasis,
but excluding stable plaque psoriasis from the definition of active disease),
active or prior documented autoimmune or inflammatory disorders requiring
chronic treatment with steroids or other
immunosuppressive treatment.

- Other invasive malignancy within 2 years prior to screening.

- Psychiatric illness/social situations/substance abuse disorders that would
limit compliance with study requirements, substantially increase risk of
incurring AEs, or compromise the ability of the participant to give written
informed consent.

Prior/Concomitant Therapy
- Current or prior use of immunosuppressive medication within 14 days before
the first dose of investigational product is excluded. The following are
exceptions to this criterion:
(a) Intranasal, inhaled, topical steroids, or local steroid injections (eg,
intraarticular injection).
(b) Systemic corticosteroids at physiological doses not to exceed 10 mg/day of
prednisone or equivalent.
(c) Steroids as premedication for hypersensitivity reactions (eg, computed
tomography [CT] scan premedication).
(d) Any concurrent chemotherapy, radiotherapy, investigational, biologic, or
hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for
noncancer-related conditions (eg, insulin for diabetes and hormone replacement
therapy) is acceptable.

- Receipt of live attenuated vaccine within 30 days prior to the first dose of
study intervention. Note: Participants should not receive live vaccine while
receiving study intervention and up to 30 days after the last dose of study
intervention. COVID-19 vaccination should not be given for 72 hours prior to
administration of the first dose of IP or during the DLT period.

Prior/Concurrent Clinical Study Experience
- Concurrent enrolment into another interventional clinical trial, unless it is
an observational (non-interventional) clinical study or during the follow-up
period of an interventional study.

- Known allergy or hypersensitivity to AZD2936 or any of the excipients of
AZD2936.

Other Exclusions
- Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca staff and/or staff at the study site).

- Pregnant or lactating female, or intend to become pregnant during the study.

- Judgement by the investigator that the individual should not participate in
the study.