A Study of MEDI9197 in Participants with Solid Tumors or CTCL and in Combination with Durvalumab and/or Palliative Radiation in Participants with Solid Tumors

Exclusion Criteria

• Inclusion Criteria for All Participants (Parts 1, 2 and 3)
• 1. Written informed consent and any locally required authorizations.
• 2. Male and female participants at least 18 years at the time of screening.
• 3. Adequate organ function within 14 days of enrollment confirmed by laboratory results.
• 4. Systemic corticosteroids at doses exceeding 12 mg/day prednisone or equivalent.
• 5. Eastern Cooperative Oncology Group 0 or 1.
• 6. Highly effective method of contraception from the date of the screening pregnancy test, and continued precautions for 6 months after the final dose of investigational product.
• 7. Baseline Child-Pugh Score of A1 to B7.
• 8. Life expectancy >=12 weeks, as estimated by Royal Marsden Hospital Score of 0 or 1 at baseline.
• 9. Participants with hepatocellular carcinoma (HCC) are eligible if the tumor is defined as nodular type 1 or 2 only.
• Additional Inclusion Criteria for Participants in Parts 1 and 3
• 10. Metastatic/locally advanced solid tumor malignancy that has progressed on, is refractory to, or for which there is no standard of care therapy.
• 11. For participants with cutaneous/subcutaneous lesions, participants must have more than one measurable target lesion, at baseline, with a minimum of one lesion that meets protocol specified criteria.
• 12. For participants with deep-seated lesions, participants must have more than one measurable target lesion at baseline (RECIST v1.1), with a minimum of one deep-seated lesion suitable for image-guided injection and that meets protocol specified criteria.
• Additional Inclusion Criteria for Participants in Part 2 (Closed to Enrollment as of Protocol Amendment 6)
• 13. Clinical diagnosis of CTCL, including documentation of a skin biopsy with histological findings consistent with CTCL or unconfirmed diagnosis of CTCL with confirmation biopsy at screening.
• 14. Stage IB, IIA, or IIB disease: T1, T2 or T3 (patches, plaques or tumors) with measurable lesions.
• 15. Previous treatment with at least one standard therapy used to treat the stage of disease at study entry; Stage IB, IIA or IIB CTCL.
• 16. Measurable skin disease with at least 2 lesions amenable to response assessment.
• 17. At least one lesion must be amenable to injection, ie, >= 1.5 cm in the longest diameter.
• Any of the following would exclude the subject from participation in the study:
• 1. Participants who have received prior immunotherapy [(including but not limited to CTLA-4, oncolytic virus, oncolytic peptide-all require 100 day washout), programmed death ligand (PDL) -1, or programmed cell death 1 antagonists-both require 14 day washout)] are NOT permitted to enroll, with protocol exceptions.
• 2. Pregnant or lactating.
• 3. Active bacterial, fungal, or viral infections, including chronic or active hepatitis B, chronic or active hepatitis C, or active hepatitis A. Prior documented infections must have resolved.
• 4. Active or prior documented autoimmune or inflammatory disorders, with exceptions per protocol. Includes known allergy to sesame oil and/or nuts.
• 5. Immune-deficiency states - myelodysplastic disorders, marrow failures, human immunodeficiency virus (HIV) infection, history of solid organ transplant or bone marrow allograft, or recent pregnancy.
• 6. Requires continuous (daily) anticoagulation or antiplatelet therapy (including anti aggregants), acetylsalicylic acid (ASA) or nonsteroidal anti-inflammatory drugs (NSAIDs).
• 7. History of coagulopathy resulting in uncontrolled bleeding or other bleeding disorders.
• 8. Rapidly progressing disease per protocol.
• 9. Untreated or uncontrolled central nervous system (CNS) involvement.
• 10. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment; with exceptions per protocol.
• 11. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to National Cancer Institute Common Terminology Criteria for Adverse Events v4.03 Grade 0 or 1, with exception of alopecia, vitiligo.
• 12. Uncontrolled concurrent illness.
• 13. Cardiac exclusions: New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled hypertension, acute coronary syndrome within 6 months, clinical important cardiac arrhythmia, mean QTC interval corrected for heart rate >500ms.
• 14. Major surgery within 4 weeks prior to study entry or still recovering from prior surgery.
• 15. Receipt of live, attenuated vaccine within 28 days prior to study entry.
• 16. Receipt of any systemic anticancer therapy not mentioned above within the last 2 weeks or 5 half-lives.
• 17. Cognitive disorder such that informed consent cannot be obtained directly from the subject
• 18. Subjects who have previously participated in this study and received MEDI9197, or concurrent enrollment in another clinical study involving an investigational treatment.
• 19. Subjects who have received prior toll-like receptor agonists, both systemic and topical.
• 20. Participants who have received prior therapeutic radiation within 28 days of dosing. All toxicities from prior radiotherapy must have resolved to =< Grade 1 or baseline prior to dosing.
• 21. Body weight < 35 kg
• 22. Participants enrolling in Part 3 (ie, receiving durvalumab) must not have a history of interstitial lung disease or pneumonitis.