A Study of MEDI5395 in Combination With Durvalumab in Participants With Select Advanced Solid Tumors

Inclusion Criteria

• The participant must consent to take precautionary measures to prevent Newcastle Disease Virus (NDV) transmission to humans and birds
• Participants must have histologic documentation of advanced solid tumor and received and have progressed, are refractory, or are intolerant to standard therapy for the specific tumor type. All participants are required to have had at least one prior line of treatment in the recurrent or metastatic setting
• Participants must have at least 1 measurable lesion and an additional non-lymph node non-target lesion that can be biopsied at acceptable risk as judged by the investigator. (Note: if a non-target lesion is not available or cannot be biopsied, a RECIST target, non-lymph node lesion, lesion >= 2 cm in longest diameter may be used for non-excisional biopsy
• All participants must consent to provide tumor tissue for correlative studies
• The ECOG performance status of 0 to 1
• Adequate organ function
• Use of highly effective contraception (females) or male condom plus spermicide (males)

Exclusion Criteria

• Rapidly progressing disease defined as a participant that cannot tolerate a break of at least 8 weeks from systemic anticancer therapy.
• Primary central nervous system (CNS) disease is excluded
• Participants who have received prior check point inhibitor immunotherapy within 28 days and/or oncolytic virus therapy within 90 days prior to the first dose of MEDI5395
• Unresolved toxicities from prior anticancer therapy that led to permanent discontinuation of prior immunotherapy or that required immunosuppression other than corticosteroids
• History of severe allergic reactions to any of the study drug components
• Infectious disease exclusions including tuberculosis, Human immunodeficiency virus (HIV), hepatitis A, B or C, active bacterial, fungal or viral infections plus receipt of live attenuated vaccine prior to first dose of MEDI5395. (NOTE: Participants with evidence of fully recovered past hepatitis B infection who developed immunity OR hepatitis B/C with undetectable virus load and are on medications may be permitted).
• Positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic test at screening
• Any conditions requiring use of any systemic immunosuppressant including systemic corticosteroids, methotrexate, azathioprine, tumor necrosis factor (TNF) inhibitor, and/or interleukin 6 (IL-6) blockers
• Active autoimmune disease or chronic inflammatory condition (Exceptions include vitiligo, alopecia, hypothyroidism on stable treatment, diverticulosis, controlled celiac disease, and chronic skin conditions not requiring systemic therapy)
• Active acquired immune-deficiency states
• Participants who are regularly exposed to poultry or birds
• Current active hepatitis or biliary disease (except for Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease)
• Clinically significant pulmonary disease and cardiac disease
• Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of participant safety or study results.