Nivolumab (Opdivo®) Plus ABI-009 (Nab-rapamycin) for Advanced Sarcoma

The primary objective of this study is to investigate the maximum tolerated dose of ABI-009,
an mTOR inhibitor, when given sequentially with nivolumab in advanced UPS, LPS, CS, OS and
Ewing sarcoma.

The secondary objectives are to investigate the disease control rate (DCR) and progression
free survival (PFS) using nivolumab/ABI-009 combination therapy in advanced UPS, LPS, CS, OS
and Ewing sarcoma.

The exploratory objectives are (1) To correlate progression free survival (PFS) based on
Immune-related Response Criteria (irRECIST) with that based on RECIST v1.1, and (2) To
correlate PFS with PD-1 and PD-L1 expression in patients' tumors.

Inclusion Criteria:

A patient will be eligible for inclusion in this study only if all of the following
criteria are met:

1. Patients must have a histologically confirmed diagnosis of UPS, LPS, CS, OS or Ewing
sarcoma that is either metastatic or locally advanced and for which surgery is not a
recommended option.

2. Patients must have one or more measurable target lesions by CT scan or MRI. Measurable
disease by RECIST v1.1.

3. Patients must not have been previously treated with a PD-1 inhibitor in combination
with an mTOR inhibitor.

4. Prior treatment (investigational or other), chemotherapy, radiotherapy, surgery, or
other therapeutic agents (except immunotherapy and mTOR inhibitors) is allowed, if
completed after 5 half-lives or ≥28 days prior to enrollment, whichever is shorter.

5. Eligible patients, 18 years or older, with Eastern Cooperative Oncology Group (ECOG)
performance status 0 or 1.

6. Patients must have the following blood chemistry levels at screening (obtained ≤14
days prior to enrollment (local laboratory):

1. total bilirubin ≤1.5 x upper limit of normal (ULN) mg/dl

2. AST ≤2.5 x ULN (≤5 x ULN if attributable to liver metastases)

3. serum creatinine ≤1.5 x ULN

7. Adequate biological parameters as demonstrated by the following blood counts at
screening (obtained ≤14 days prior to enrollment, local laboratory):

1. Absolute neutrophil count (ANC) ≥1.5 × 109/L;

2. Platelet count ≥100,000/mm3 (100 × 109/L);

3. Hemoglobin ≥9 g/dL.

8. Serum triglyceride <300 mg/dL; serum cholesterol < 350 mg/dL.

9. Male or non-pregnant and non-breast feeding female:

Females of child-bearing potential must agree to use effective contraception without
interruption from 28 days xprior to starting IP and while on study medication and have
a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing
pregnancy testing during the course of the study, and after the end of study
treatment. A second form of birth control is required even if she has had a tubal
ligation.

Male patients must practice abstinence or agree to use a condom during sexual contact
with a pregnant female or a female of childbearing potential while participating in
the study. A second form of birth control is required even if he has undergone a
successful vasectomy.

10. Life expectancy of >3 months, as determined by the investigator.

11. Ability to understand and sign informed consent.

12. Willingness and ability to comply with scheduled visits, laboratory tests, and other
study procedures.

Exclusion Criteria:

A patient will not be eligible for inclusion in this study if any of the following criteria
apply:

1. Concurrent or prior immunotherapy with a PD-1 inhibitor in combination with an mTOr
inhibitor.

2. Known active uncontrolled or symptomatic central nervous system (CNS) metastases. A
patient with controlled and asymptomatic CNS metastases may participate in this study.
As such, the patient must have completed any prior treatment for CNS metastases ≥28
days (including radiotherapy and/or surgery) prior to start of treatment in this study
and should not be receiving chronic corticosteroid therapy for the CNS metastases.

3. Active gastrointestinal bleeding.

4. Pre-existing thyroid abnormality is allowed provided thyroid function can be
controlled with medication.

5. Uncontrolled serious medical or psychiatric illness. Patients with a "currently
active" second malignancy other than non-melanoma skin cancers, carcinoma in situ of
the cervix, resected incidental prostate cancer (staged pT2 with Gleason Score ≤ 6 and
postoperative PSA <0.5 ng/mL), or other adequately treated carcinoma-in-situ are
ineligible. Patients are not considered to have a "currently active" malignancy if
they have completed therapy and are free of disease for ≥1 year).

6. Liver-directed therapy within 2 months of enrollment. Prior treatment with
radiotherapy (including radio-labeled spheres and/or cyberknife, hepatic arterial
embolization (with or without chemotherapy) or cyrotherapy/ablation) is allowed if
these therapies did not affect the areas of measurable disease being used for this
protocol.

7. Recent infection requiring systemic anti-infective treatment that was completed ≤14
days prior to enrollment (with the exception of uncomplicated urinary tract infection
or upper respiratory tract infection).

8. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy.

9. Unstable coronary artery disease or myocardial infarction during preceding 6 months.

10. Receiving any concomitant antitumor therapy.

11. Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary
hypertension.

12. Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving
the first dose of ABI-009. Additionally, use of any known CYP3A4 substrates with
narrow therapeutic window (such as fentanyl, alfentanil, astemizole, cisapride,
dihydroergotamine, pimozide, quinidine, terfanide) within the 14 days prior to
receiving the first dose of ABI-009.

13. Known Human Immunodeficiency Virus (HIV).

14. Active Hepatitis B or Hepatitis C.

15. Non-oncology vaccine therapy used for prevention of infectious disease within 4 weeks
of trial enrollment

16. Autoimmune disease including rheumatoid arthritis, systemic progressive sclerosis
(scleroderma), systemic lupus erythematosus, autoimmune vasculitis and motor
neuropathy considered to be of autoimmune origin (e.g. Guillain-Barre Syndrome)

17. Systemic immunosuppression, including HIV positive status with or without AIDS

18. Skin rash (psoriasis, eczema) affecting > 25% body surface area

19. Inflammatory bowel disease (Crohn's or ulcerative colitis)

20. Ongoing or uncontrolled diarrhea within 4 weeks of trial enrollment

21. Recent history of acute diverticulitis, intraabdominal abscess or gastrointestinal
obstruction within 6 months of trial enrollment, which are known risk factors for
bowel perforation

22. Current, active or previous history of heavy alcohol abuse

23. Pituitary endocrinopathy

24. Adrenal insufficiency or excess