A Phase I/Ib Study of NIZ985 in Combination With PDR001 in Adults With Metastatic Cancers

Inclusion Criteria:

1. Histologically confirmed solid tumor malignancy that is metastatic or unresectable and
have progressed on at least 1 prior therapy and for whom standard curative or
palliative measures do not exist or are associated with minimal subject survival
benefit.

Evaluable or measurable disease, defined as by Response Evaluation Criteria in Solid
Tumors (RECIST).

2. Recovered to ≤ grade 1 NCI CTCAE version 4.0 from toxicity of prior chemotherapy or
biologic therapy administered more than 4 weeks earlier.

3. Subjects on bisphosphonates for any cancer or on hormone therapy for prostate cancer
may continue this therapy. However, subjects with prostate cancer must have confirmed
metastatic disease that has progressed despite hormonal therapy producing castrate
levels of testosterone.

4. Age ≥18 years.

5. ECOG performance status ≤1 (Karnofsky ≥70%).

6. Normal organ and marrow function:

- leukocytes ≥3,000/mcL

- absolute neutrophil count (ANC) ≥1,500/mcL

- platelets ≥100,000/mcL

- total bilirubin within normal institutional limits

- AST/ALT ≤2.5 × ULN

- creatinine <1.5 × institutional ULN OR

- creatinine clearance ≥60 mL/min/1.73 m2 for subjects with serum creatinine levels
>1.5 × higher than ULN.

7. DLCO/VA and FEV1 ≥ 50% of predicted on PFTs.

8. Subjects with inactive central nervous system (CNS) metastasis are eligible..

9. Women of child-bearing potential and men must agree to use adequate contraception
prior to study entry, during the treatment portion of the study and for 4 months after
completion of hetIL-15 administration.

10. Able to provide written informed consent.

11. Life expectancy > 3 months.

Exclusion Criteria:

1. Prior IL-15 treatment or cytotoxic therapy, immunotherapy, radiotherapy, major
surgery, antitumor vaccines or monoclonal antibodies in the 4 weeks prior or for
checkpoint inhibitors such as anti-CTLA-4 or anti PD1/PD-L1 or nitrosoureas or
mitomycin C for 6 weeks prior to C1D1.

2. Primary brain cancers or active CNS metastases should be excluded from this clinical
trial

3. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to hetIL-15.

4. Concurrent anticancer therapy (including other investigational agents) with the
exception of hormone therapy for prostate cancer.

5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, cognitive impairment, active substance abuse, or psychiatric
illness/social situations that, in the view of the Investigator, would preclude safe
treatment or the ability to give informed consent and limit compliance with study
requirements.

6. HIV positive patients.

7. Positive hepatitis B or C serology.

8. History of severe asthma or absolute requirement for chronic inhaled corticosteroid
medications.

9. History of autoimmune disease, with the exception of an autoimmune event associated
with prior ipilimumab (anti-CTLA-4) therapy that has been completely resolved for more
than 4 weeks prior to C1D1.