business decision

Phase I/Ib multicenter clinical trial. Single agent dose escalation of NIZ985 followed by expansion. Second escalation of NIZ985 in combination with PDR001 followed by expansion

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.