A Phase 1/2 Study of Motolimod (VTX-2337) and MEDI4736 in Subjects With Recurrent, Platinum-Resistant Ovarian Cancer for Whom Pegylated Liposomal Doxorubicin (PLD) is Indicated

Inclusion Criteria:

1. Subjects must have recurrent or persistent platinum-resistant epithelial ovarian,
fallopian tube, or primary peritoneal carcinoma with measureable disease (as defined
by RECIST 1.1.) after first or second line platinum-based chemotherapy, for which
treatment with PLD is indicated. Platinum-based therapy is defined as treatment with
carboplatin, cisplatin or another organoplatinum compound. Platinum-resistant is
defined as having a platinum-free interval (PFI) of < 12 months after first- or
second-line platinum-based chemotherapy, or having disease progression while receiving
second-line platinum-based chemotherapy.

Subjects are allowed to have received, but are not required to have received:

- one additional cytotoxic regimen and/or PARP inhibitor for management of
recurrent or persistent disease.

- biologic therapy (e.g., bevacizumab) as part of their primary treatment regimen
or part of their treatment for management of recurrent or persistent disease.

2. Histologic documentation of the original primary tumor.

3. Documented radiographic disease progression < 12 months after the last dose of first-
or second-line platinum-based chemotherapy.

4. Subjects in Phase 2 must have disease amenable to biopsy and must be willing to
undergo pre- and post-treatment tumor biopsies. Optional for Phase 1.

Note: archival tissue will be requested for all subjects preferably from primary tumor
site prior to cancer treatment; however, archival tissue is not a requirement for
study entry.

5. ECOG performance status of 0 or 1.

6. Laboratory parameters for vital functions should be in the normal range. Laboratory
abnormalities that are not clinically significant are generally permitted, except for
the following laboratory parameters, which must be within the ranges specified,
regardless of clinical significance:

- Hemoglobin: ≥ 9 g/dL

- Neutrophil count: ≥ 1.5 x 109/L

- Platelet count: ≥ 100,000/mm3

- Serum creatinine, ≤ 1.5x Institutional Upper Limit of Normal (ULN), or Creatinine
Clearance ≥ 50 mL/min (by Cockcroft-Gault formula)

- Serum bilirubin: ≤ 1.2 mg/dL

- AST/ALT: ≤ 2.5 x ULN

- Alkaline phosphatase: ≤ 2.5 x ULN

7. Age ≥18 years.

8. Able and willing to give valid written informed consent.

9. Body weight > 30 kg

Exclusion Criteria:

1. Prior exposure to doxorubicin, PLD or any other anthracycline, motolimod and other TLR
agonists, MEDI4736 or checkpoint inhibitors, such as anti-CTLA4 and
anti-PD1/anti-PD-L1 antibodies.

2. Subjects with platinum-refractory disease, defined as disease progression while
receiving first line platinum-based therapy.

3. Clinically significant persistent immune-related adverse events following prior
therapy.

4. Subjects with history or evidence upon physical examination of CNS disease, including
primary brain tumor, seizures not controlled with standard medical therapy, any brain
metastases, or, within six months prior to Day 1 of this study, history of
cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or
subarachnoid hemorrhage.

5. Subjects with clinically significant cardiovascular disease. This includes:

1. Resisted hypertension

2. Myocardial infarction or unstable angina within 6 months prior to Day 1 of the
study.

3. History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic
medications, except for atrial fibrillation that is well controlled with
anti-arrhythmic medication.

4. Baseline ejection fraction ≤ 50% as assessed by echocardiogram or MUGA.

5. New York Heart Association (NYHA) Class II or higher congestive heart failure.

6. Grade 2 or higher peripheral ischemia, except for brief (< 24 hrs) episodes of
ischemia managed non-surgically and without permanent deficit.

6. History of pneumonitis or interstitial lung disease.

7. Active, suspected or prior documented autoimmune disease (including inflammatory bowel
disease, celiac disease, Wegner's granulomatosis, active Hashimoto's thyroiditis,
rheumatoid arthritis, lupus, scleroderma and its variants, multiple sclerosis,
myasthenia gravis). Vitiligo, type I diabetes mellitus, residual hypothyroidism due to
autoimmune condition only requiring hormone replacement, psoriasis not requiring
systemic treatment, or conditions not expected to recur in the absence of an external
trigger are permitted.

8. Other malignancy within 2 years prior to Day 1 of the study, except for those treated
with surgical intervention only.

9. Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who
require drainage gastrostomy tube and/or parenteral hydration or nutrition.

10. Known immunodeficiency or HIV, Hepatitis B or Hepatitis C positivity.

11. History of severe allergic reactions to any unknown allergens or components of the
study drugs.

12. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding
disorders).

13. Prior treatment in any other interventional clinical trial within 4 weeks prior to Day
1 of the study.

14. Mental impairment that may compromise compliance with the requirements of the study.

15. Lack of availability for immunological and clinical follow-up assessment.

16. Women who are breastfeeding or pregnant as evidenced by positive serum pregnancy test

17. Subjects unwilling to use acceptable methods of contraception.

-Female subjects should refrain from breastfeeding throughout this period.

18. Any condition that, in the clinical judgment of the treating physician, is likely to
prevent the subject from complying with any aspect of the protocol or that may put the
subject at unacceptable risk.

19. Subjects must not donate blood while on study and for at least 90 days following the
last MEDI4736 treatment.

20. History of allogeneic organ transplant