• Number of subjects with adverse events (AEs) serious adverse events (SAEs) and dose limiting toxicities (DLTs). [ Time Frame: From time of informed consent until 90 days after the last dose of investigational product (MEDI1191 or durvalumab). ]
  The occurrence of DLTs will be used to establish the maximum tolerated dose (MTD) of MEDI1191.
• Objective response rate (ORR) in patients within expansion arms. [ Time Frame: Estimated to be from time of informed consent up to 3.5 years. ]
  The ORR is defined as the proportion of subjects with confirmed response (CR) or confirmed partial response (PR).

• Number of advanced solid tumor subjects with adverse events (AEs) serious adverse events (SAEs) and dose limiting toxicities (DLTs). [ Time Frame: From time of informed consent until 90 days after the last dose of investigational product (MEDI1191 or durvalumab). ]
  The occurrence of DLTs will be used to establish the maximum tolerated dose (MTD) of MEDI1191.
• Objective response rate (ORR) in advanced solid tumor subjects. [ Time Frame: Estimated to be from time of informed consent up to 3.5 years. ]
  The ORR is defined as the proportion of subjects with confirmed response (CR) or confirmed partial response (PR).
• Disease Control Rate (DCR). [ Time Frame: Estimated to be from time of informed consent up to 3.5 years. ]
  The DCR will be estimated by the proportion of disease control. Disease control is defined as CR, PR or stable disease.
• Duration of Response (DoR). [ Time Frame: Estimated to be from time of informed consent up to 3.5 years. ]
  The DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.
• Time To Response (TTR). [ Time Frame: Estimated to be from time of informed consent up to 3.5 years . ]
  The TTR is defined as the time from the start of treatment with any investigational product until the first documentation of a subsequently confirmed objective response.
• Progression Free Survival (PFS). [ Time Frame: Estimated to be from time of informed consent up to 3.5 years. ]
  PFS will be measured from the start of treatment with any investigational product until the first documentation of disease progression or death due to any cause, whichever occurs first.
• Overall Survival (OS). [ Time Frame: Estimated to be from time of informed consent up to 3.5 years. ]
  OS will be measured from the start of treatment with investigational product until death due to any cause.
• Maximum observed concentration (Cmax) of MEDI1191 and durvalumab [ Time Frame: From first dose of MEDI1191 through to 30 days after last dose of investigational product. ]
  The endpoints for assessment of PK of MEDI1191 and durvalumab include individual MEDI1191 and durvalumab concentrations in serum at different timepoints after administration.
• Area under the concentration-time curve (AUC) of MEDI1191 [ Time Frame: From first dose of MEDI1191 through to 30 days after last dose of investigational product. ]
  The endpoints for assessment of PK of MEDI1191 include MEDI1191 concentrations in serum at different timepoints after administration.
• Clearance of MEDI1191 [ Time Frame: From first dose of MEDI1191 through to 30 days after last dose of investigational product. ]
  The endpoints for assessment of PK of MEDI1191 include MEDI1191 concentrations in serum at different timepoints after administration.
• Immunogenicity of MEDI1191 [ Time Frame: From first dose of MEDI1191 through to 3.5 years after last dose of investigational product. ]
  The endpoints for assessment of immunogenicity of MEDI1191 include the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).

• Solid Tumors
• Cancer

• Biological: MEDI1191
  Subjects will receive MEDI1191 (at least twice)
• Biological: Durvalumab
  Subject will receive durvalumab every 4 weeks

• Experimental: MEDI1191 escalation in combination with durvalumab
  MEDI1191 escalation in sequential and concurrent combination with durvalumab
  Interventions:

  • Biological: MEDI1191
  • Biological: Durvalumab
• Experimental: MEDI1191 expansion in combination with durvalumab
  MEDI1191 expansion in concurrent combination with durvalumab
  Interventions:

  • Biological: MEDI1191
  • Biological: Durvalumab

Inclusion Criteria:

• ECOG 0 to 1.
• Adequate organ function within 2 weeks of starting study treatment.
• Prior to the first dose of MEDI1191, subjects with central nervous system (CNS) metastases must have been treated and must be asymptomatic.
• Cessation of systemic corticosteroids at doses exceeding 12 mg/day prednisone or equivalent, methotrexate, azathioprine, ustekinumab (Stelara®), and tumor necrosis factor (TNF)-α/IL-6 blockers for at least 7 days prior to the first dose of MEDI1191.
• Subjects must have at least one lesion suitable for intratumoral dosing for superficial lesions but at least two lesion suitable for intratumoral dosing for deep-seated lesions.
• Subjects must have at least one non-injected lesion that can be measured by RECIST v1.1.
• Histologic or cytologic confirmation of advanced solid tumor.
• Received and have progressed on or refractory to at least 1 line of standard systemic therapy in the recurrent/metastatic setting.
• Highly effective method of contraception from screening, and must agree to continue using such precautions for 3 months after the final dose of investigational product.
• Nonsterilized male subjects who are sexually active with a female partner of childbearing potential must use a male condom with spermicide from Day 1 through 6 months after receipt of the final dose of investigational product.

Exclusion Criteria:

• Subjects who have received prior IL-12 either alone or as part of a treatment regimen.
• Subjects who were administered any live attenuated vaccines within 30 days prior to first MEDI1191 injection.
• Known allergy or hypersensitivity to any component of MEDI1191 or durvalumab formulations.
• Active or prior documented autoimmune disorders within the past 5 years prior to the first scheduled dose of study treatment except alopecia, hypothyroidism (stable of hormone replacement), chronic skin condition (does not require systemic therapy), and celiac disease (controlled by diet alone).
• Immune-deficiency states - myelodysplastic disorders, marrow failure states, human immunodeficiency virus infection, history of solid organ transplant, bone marrow allograft, or active tuberculosis.
• History of coagulopathy resulting in uncontrolled bleeding or other bleeding disorders.
• Require continuous anticoagulation or antiplatelet therapy (except for ≤ 100 mg acetylsalicylic acid [ASA]) which cannot be interrupted for more than 7 days for IT delivery of MEDI1191.
• Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for cancer.

• Receipt of any conventional or investigational anticancer therapy within 21 days or palliative radiotherapy within 7 days prior to the first dose of study treatment. For subjects who have received prior immunotherapy, the following additional exclusion criteria apply:

  1. Received only one dose of prior immunotherapy agent alone or as part of a combination regimen
  2. Experienced a toxicity that led to permanent discontinuation of prior immunotherapy
  3. All AEs while receiving prior immunotherapy did not resolve to ≤ Grade 1 or baseline prior to screening for this study.
  4. Experienced a ≥ Grade 3 AE (including pneumonitis) or neurologic, ocular, or cardiac AE of any grade while receiving prior immunotherapy.
  5. Required the use of additional immunosuppression other than corticosteroids for the management of an AE, or experienced recurrence of an AE if re-challenged, or is currently requiring a maintenance dose of > 12 mg prednisone or equivalent per day.
• Any toxicity from prior therapy that has not completely resolved to ≤ Grade 1 or baseline at the time of consent.
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose of MEDI1191, except intranasal, topical, inhaled corticosteroids, local steroid injections, systemic corticosteroids at physiologic doses not to exceed 12 mg/day of prednisone or equivalent, or steroids as premedication for hypersensitivity reactions.
• Cardiac exclusions: New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled hypertension, acute coronary syndrome within 6 months.
• Any condition that would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
• Uncontrolled intercurrent illness.
• Untreated, active hepatitis B or C.
• Major surgery within 4 weeks prior to first dose of MEDI1191 or still recovering from prior surgery.
• Subjects with untreated active major depression with suicidal ideation and/or plan.
• Female subjects who are pregnant, lactating, or intend to become pregnant during their participation in this study.