Study of ONT-10 and Varlilumab to Treat Advanced Ovarian or Breast Cancer

This is a two-part Phase 1b, open-label study of ONT 10 administered in combination with
varlilumab. Two different doses of varlilumab will be studied in combination with the single
agent recommended dose of ONT 10. Intermediate and/or lower doses of varlilumab or ONT-10 may
also be studied at the recommendation of the safety monitoring committee (SMC). Treatment
will be administered in cycles of 12 weeks each. All patients will receive a single dose of
cyclophosphamide on Day -3. During Cycle 1, patients will receive ONT-10 administered SC once
per week for 8 weeks followed by ONT-10 once every 6 weeks starting with Cycle 2, in
combination with varlilumab administered IV once every 3 weeks x 3 doses, and then once every
6 weeks for cycles 2 through 5.

Each cohort will enroll an initial group of 6 evaluable patients with either breast or
ovarian carcinoma. Initial enrollment into a cohort will be staggered, with the first patient
treated in any new cohort to be followed for a minimum of two weeks for the occurrence of
Unacceptable Toxicity prior to enrollment of the remaining 5 patients. Subsequent enrollment
into a cohort may then continue without a staggered schedule until 6 patients treated are
considered evaluable. Up to 24 additional evaluable patients may be enrolled and treated in
Part 2 at the RD of varlilumab and ONT-10 identified in Part 1, including approximately equal
numbers of patients with breast carcinoma (n~12) and ovarian carcinoma (n~12). Treatment in
Part 2 will follow the same schedule as in Part 1.

Inclusion Criteria:

1. Be at least 18 years of age at the time of consent

2. Life expectancy of at least 6 months, in the opinion of the investigator

3. Have histologically confirmed breast or ovarian carcinoma

4. Have evidence of persistent, recurrent, or progressive disease for which there is no
known or established treatment available with curative intent, after at least one
course of systemic therapy for locally advanced or metastatic disease , including
chemotherapy, targeted therapy (small molecule or antibody based), or hormonal therapy

5. Measurable or evaluable disease by RECIST 1.1

6. ECOG performed status of 0 or 1

7. Adequate hematologic function defined by:

8. WBC count ≥ 3.0 x 103 cells/µL

9. Lymphocyte count ≥ 0.8 x 103 cells/µL

10. Platelet count ≥ 75 x 103 /µL, and

11. Hemoglobin ≥ 9 g/dL

12. Have renal and hepatic function as defined by:

13. AST and ALT ≤ 2.5 X ULN

14. Total bilirubin ≤ 1.5 X ULN. Patients with elevated bilirubin known to be due to
Gilbert's disease may be enrolled after approval from the medical monitor, and

15. Creatinine clearance ≥ 50 mL/min

16. If female of child bearing potential, have a negative pregnancy test at screening

17. If fertile male or female of child-bearing potential, agree to consistently use a
highly effective method of birth control (including birth control pills, barrier
device, or intrauterine device, abstinence or other methods prescribed by a licensed
healthcare provider) from the time of consent through 70 days following the last dose
of study drug

18. Patient or a legally authorized representative of a patient must be able and willing
to sign informed consent document that has been approved by an IRB

Exclusion Criteria:

1. Has medical, social, or psychological factors that, in the opinion of the
Investigator, could impact safety or compliance with study procedures

2. Is pregnant, breastfeeding, or planning a pregnancy

3. Has received treatment with any systemic anticancer therapy, wide-field radiation, or
experimental agent within 4 weeks of receiving cyclophosphamide on Day -3, with the
exception of anticancer hormonal therapy, which may not be given within 2 weeks of
receiving cyclophosphamide on Day -3. All residual toxicity related to prior
anticancer therapies (excluding vitiligo, endocrinopathies on stable replacement
therapy, alopecia and Grade 2 fatigue) must resolve to Grade 1 severity or less or
return to baseline prior to receipt of study treatment.

4. Has received treatment with focal radiotherapy within 2 weeks, or radiopharmaceuticals
(e.g., strontium, samarium) within 8 weeks of receiving cyclophosphamide on Day -3

5. Has untreated or uncontrolled CNS metastases, including patients who require
glucocorticoid therapy for CNS metastases

6. Has received prior treatment with ONT-10 or varlilumab, or prior treatment with other
MUC1 vaccines or CD27-targeted agents

7. Has active autoimmune disease or a documented history of autoimmune disease, or
history of potential autoimmune syndrome that required systemic steroids or
immunosuppressive medications, except for patients with vitiligo, endocrinopathies,
type 1 diabetes, or patients with resolved childhood asthma/atopy or other syndromes
which would not be expected to recur in the absence of an external trigger (e.g.,
drug-related serum sickness or post-streptococcal glomerulonephritis). Patients with
mild asthma who require intermittent use of bronchodilators (such as albuterol) who
have not been hospitalized for asthma in the preceding 3 years will not be excluded
from this study.

8. Has recognized immunodeficiency disease, including cellular immunodeficiencies,
hypogammaglobulinemia, or dysgammaglobulinemia, and/or other hereditary congenital
immunodeficiencies

9. Has any pre-existing medical condition requiring systemic chronic steroid or
immunosuppressive therapy

a) Inhaled corticosteroids for COPD or topical steroids are allowed

10. Known to be positive for HIV, or to have active hepatitis B, or hepatitis C, or have
active infection of any kind requiring systemic therapy

11. Administration of any other vaccine ≤ 4 weeks of receiving cyclophosphamide on Day -3

12. Underlying medical condition that, in the Investigator's opinion, will make the
administration of study treatment hazardous or obscure the interpretation of toxicity
determination of adverse events. This includes other prior malignancy, except for
adequately treated basal or squamous cell skin cancer or in situ cancer; or any other
cancer from which the patient has been disease-free for at least 3 years.

13. Significant cardiovascular disease including unstable angina pectoris, uncontrolled
hypertension (persistent systolic blood pressure > 150 mmHg and/or diastolic blood
pressure > 100 mmHg on antihypertensive medications) or arrhythmia, congestive heart
failure (NYHA Class III or IV) related to primary cardiac disease, ischemic or severe
valvular heart disease, or myocardial infarction within 6 months prior to the first
dose of study treatment