A Multiple Ascending Dose Study of MEDI7247 in Advanced or Metastatic Solid Tumors

Inclusion Criteria:

1. Confirmed diagnosis of advanced or metastatic select solid tumors and either
progression on or documented intolerance to standard therapies

2. Age ≥ 18 years at the time of screening.

3. Written informed consent and any locally required authorization

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

5. At least 1 measurable target lesion by CT or MRI per RECIST Version 1.1 (excluding
mCRPC)

6. Adequate Liver Function: Aspartate Aminotransferase (AST) and Alanine Aminotransferase
(ALT) ≤ 2.5 × ULN (upper limit normal), Albumin > 3 g/dL, and serum total bilirubin
(TBL) ≤ 1.5 × ULN; (unless bilirubin rise is due to Gilbert's syndrome, hepatic
metastases or of non-hepatic origin, in which case TBL ≤ 3 × ULN is allowed)

7. Creatinine Clearance (CrCL) ≥ 40 mL/min

8. Adequate Hematopoesis: Absolute Neutrophil Count (ANC) ≥ 1,500/μL, Platelets ≥
100,000/μL, and Hgb ≥ 9 g/dL unassisted by transfusion or growth factor within 14 days
of screening

9. Provision of archival or fresh tumor tissue at screening

10. Female patients of childbearing potential who are sexually active with a nonsterilized
male partner must use at least one highly effective method of contraception, and must
agree to continue using such precautions for 90 days after the last dose of
investigational product.

11. Nonsterilized male patients who are sexually active with a female partner of
childbearing potential must use a male condom plus spermicide from 7 days
post-screening and for 90 days after receipt of the last dose of investigational
product.

Exclusion Criteria:

1. Active central nervous system (CNS) metastases, unless adequately treated and patients
have neurologically returned to baseline (except for residual signs or symptoms
related to the CNS treatment) and prednisolone 10 mg or less for more than 2 weeks
prior to enrollment. For SCLC, a brain MRI scan that was conducted ≤ 28 days from Day
1 is required.

2. Residual toxicity from prior anticancer therapy not resolved to NCI CTCAE v4.03 Grade
1, with the exception of alopecia/vitiligo at the time of first dose of
investigational product. For patients previously receiving immunotherapy, toxicities
that are unlikely to recover to Grade 1.

3. Royal Marsden Hospital (RMH) prognostic score 2 and 3 at baseline.

4. Treatment with anticancer therapy including chemotherapy, radiation therapy,
immunotherapy, biologic, or any investigational therapy within 21 days, or prior
palliative radiotherapy within 2 weeks of the first dose of investigational product.

5 Prior treatment with other Pyrrolobenzodiazepine-Antibody Drug Conjugates.

6 History of previous malignancies (except for locally curable cancers) unless a complete
remission was achieved at least 3 years prior to study entry AND no additional therapy is
required during the study period (except adjuvant hormonal therapy and bisphosphonate).

7. Failure to recover from major surgery or significant traumatic injury within 21 days of
first dose of study treatment.

8 History of hepatic sinusoidal obstruction syndrome, also called veno-occlusive disease 9.
History of capillary leak syndrome. 10 Blood transfusion within 14 days of study entry
except when needed for disease related anemia.

11. New York Heart Association classes III-IV congestive heart failure or serious cardiac
arrhythmia requiring treatment, history of myocardial infarction, unstable angina, vascular
stent, or coronary artery bypass graft within 6 months of the first dose of investigational
product. 12. Active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or
hepatitis C virus (HCV) infections at the time of screening.

13. Current severe active systemic disease including active concurrent malignancy 14.
Pregnancy and/or breastfeeding at time of screening 15. Concurrent enrollment in anther
clinical study involving an investigational treatment that is not an extension of another
MedImmune study with the same investigational product.