A Phase 1 Study to Evaluate MEDI6383 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors

This is a Phase 1, multicenter, open-label, dose-escalation, and dose-expansion study to
evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics, and
antitumor activity of MEDI6383 alone and in combination with MEDI4736 in adult subjects with
recurrent or metastatic solid tumors.

Inclusion Criteria:

1. Male and female subjects; age ≥ 18

2. Written informed consent must be obtained

3. Subjects must meet the following criteria:

1. Have recurrent or metastatic solid tumors

2. Must have received and have progressed, are refractory, or are intolerant to
standard therapy appropriate for the specific tumor type. Subjects should not
have received more than 5 prior lines of therapy for recurrent or metastatic
disease including both standards of care and investigational therapies

4. Subjects must have at least 1 lesion

5. Subjects must consent to provide archived tumor specimens and / or tumor biopsy for
correlative biomarker studies.

6. Eastern Cooperative Oncology Group performance score of 0 or 1

7. In the opinion of the invesgator likely to complete ≥ 8 weeks of treatment.

8. Adequate organ function as determined by:

i. Absolute neutrophil count ≥ 1.5 x 109/L (1,500/mm3) ii.Platelet count ≥ 100 x 109/L
(100,000/mm3) iii.Hemoglobin ≥ 9.0 g/dL within first 2 weeks prior to first dose of
investigational product iv.Calculated creatinine clearance* (CrCl) or 24 hour urine
CrCl > 50 mL/min v.Total bilirubin ≤ 1.5× ULN; for subjects with documented/suspected
Gilbert's disease, bilirubin ≤ 3× ULN vi.Aspartate transaminase (AST) and alanine
transaminase (ALT) ≤ 2.5× ULN vii.Serum Electrolytes within normal limits

9. Females of childbearing potential who are sexually active with a nonsterilized male
partner must use 2 methods of highly effective contraception from screening, and must
agree to continue using such precautions for 90 days after the final dose of
investigational product; 10) Nonsterilized males who are sexually active with a female
partner of childbearing potential must use a highly effective method of contraception
from Day 1 through 90 days after receipt of the final dose of investigational product

Exclusion Criteria:

1. Prior treatment with TNFRSF agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR)
.

2. Subjects who have received prior therapy with regimens containing CTLA-4, PDL-1, or
PD-1 antagonists are NOT permitted to enroll unless all of the following apply:

- Must not have experienced a toxicity that led to permanent discontinuation of
prior immunotherapy

- All AEs while receiving prior immunotherapy must have resolved to ≤ Grade 1 or
baseline prior to screening for this study.

3. Must not have experienced a ≥ Grade 3 AE or neurologic or ocular AE of any grade while
receiving prior immunotherapy

4. History of severe allergic reactions to any unknown allergens or any components of the
study drug formulations

5. Active or prior documented autoimmune disease within the past 2 years.

6. Untreated central nervous system metastatic disease l

7. Concurrent enrollment in another clinical study, unless it is an observational (non
interventional) clinical study or the follow-up period of an interventional study

8. Receipt of anticancer therapy within 28 days prior to the first dose of
Investigational Product

9. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer
treatment.

10. Unresolved toxicities from prior anticancer therapy

11. Systemic anticoagulation or daily aspirin dose exceeding 325 mg per day

12. Current or prior use of immunosuppressive medication within 14 days prior to the first
dose of MEDI6383. )

13. History of primary immunodeficiency, solid organ transplantation, or tuberculosis

14. True positive test results for human immunodeficiency virus (HIV) or hepatitis B or C

15. Receipt of live, attenuated vaccine within 28 days prior to the first dose of
investigational products )

16. Pregnant or breastfeeding women

17. Major surgery (as defined by the investigator) within 4 weeks prior to first dose of
MEDI6383 or still recovering from prior surgery. Local surgery of isolated lesions for
palliative intent is acceptable

18. Other invasive malignancy within 2 years