A Phase 1 Study of Recombinant Human IL15 (rhIL15) in Adults With Advanced Solid Tumors: Melanoma, Renal Cell, Non-Small Cell Lung and Head and Neck Cancer

Inclusion Criteria:

- Patients must have histological or cytological confirmed malignancy in the following
disease groups: melanoma, non-small cell lung carcinoma, renal cell carcinoma or head
and neck carcinoma, for which no standard effective or curative options are available

- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

- Documented evidence of disease progression during 6 month period prior to the time of
enrollment

- Prior therapy requirements:

- At least >= 1 prior completed chemotherapy regimen

- At least 4 weeks from last dose of prior chemotherapy with resolution of the
acute toxic effects of the therapy

- At least 2 weeks from completion of prior radiation therapy

- At least 4 weeks from last dose of prior investigational therapy

- Not receiving any current anti-cancer therapy

- At least 4 weeks from last dose of interferon or interleukin (IL)-2 therapy

- At least 12 weeks from completion of antibody therapy with anti-checkpoint
antibodies, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and
anti-programmed cell death 1 (PD1)

- At least 4 weeks from last dose of prior other biologic agents

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky >=
70%)

- Absolute lymphocytes >= 800/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin within normal institutional limits

- Prothrombin time (PT)/partial thromboplastin time (PTT) =< 1.5 x upper limit of
normal (ULN)

- Hemoglobin (Hgb) >= 10 g/dL

- Alkaline phosphatase =< 2.5 x ULN

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2 x institutional upper limit of normal

- Serum creatinine < 1.5 x ULN or creatinine clearance > 60 mL/min/1.73 m2 for patients
with creatinine levels above institutional normal

- Thyroid function thyroxine (T4), thyroid stimulating hormone (TSH) within normal
limits; pre-existing hypothyroidism is acceptable as long as patient has been stable
on thyroid replacement for four months prior to entering the study

- No known central nervous system (CNS) metastases or neurological symptoms possibly
related to active CNS metastasis

- Females of childbearing potential must have a negative pregnancy test within 48 hours
prior to initiation of protocol therapy; note: subjects are considered not of child
bearing potential if they are surgically sterile, they have undergone a hysterectomy,
bilateral tubal ligation, or bilateral oophorectomy or they are postmenopausal;
menopause is the age associated with complete cessation of menstrual cycles, menses,
and implies the loss of reproductive potential; by a practical definition, it assumes
menopause after 1 year without menses with an appropriate clinical profile at the
appropriate age

- Ability to understand and the willingness to sign a written informed consent document

- No history of any hematopoietic malignancy

- No active (as defined by requiring immunosuppressive therapy) or history of
clinically significant autoimmune disease (as defined by previously requiring
immunosuppressive therapy)

- No evidence of a clinically significant active infection

- No systemic or inhaled corticosteroids or immunosuppressive therapy within 30 days
prior to initiation of protocol therapy; note: use of topical corticosteroids and/or
eye drops containing glucocorticosteroids is acceptable

- No history of severe asthma, as defined by prior or current use of systemic
corticosteroids for disease control, with the exception of physiological replacement
doses of cortisone acetate or equivalent, as defined by a dose of 10mg or less; note:
history of mild asthma not requiring daily therapy is eligible

- No history of pulmonary disease such as emphysema or chronic obstructive pulmonary
disease (COPD), (forced expiratory volume in one second [FEV1] >= 2L or >= 75% of
predicted for height and age); pulmonary function tests (PFTs) are required in
patients with significant pulmonary or smoking history

- No history of human immunodeficiency virus (HIV), active or chronic hepatitis B,
hepatitis C or human T-cell lymphotropic virus (HTLV-I) infection; note: a positive
hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface
antibody [HBsAb] positive and hepatitis B core antibody [HBcAb] negative), or a fully
resolved acute hepatitis B virus (HBV) infection is not an exclusion criterion

- Females of childbearing potential and males must be willing to use an effective
method of contraception (hormonal, barrier method of birth control or abstinence)
from the time the consent is signed, during the duration of study participation and 4
months after discontinuation of protocol therapy

- Females must not be breastfeeding

- No evidence of clinically significant congestive heart failure, (ejection fraction of
45% or greater)

- No platelet or blood transfusions within two weeks of obtaining baseline laboratory
values

- No blood modifiers while enrolled in the study (growth factors such as
erythropoiesis-stimulating agent [ESA], filgrastim [G-CSF], platelet or blood
transfusions)

Exclusion Criteria:

- Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or
mitomycin C), or radiotherapy within 2 weeks prior to entering the study or those who
have not recovered from adverse events due to agents administered more than 4 weeks
earlier

- Class II or greater congestive heart failure as described in the New York Heart
Association Functional Classification criteria

- Patients with primary brain cancer or known brain metastases should be excluded from
this clinical trial

- Patients who have received prior anti-CTLA4 or anti-PD1 therapy less than 12 weeks
prior to enrollment

- Patients who have received prior biologic agents less than 4 weeks prior to
enrollment

- Patients who have received prior interferon or IL-2 therapy less than 4 weeks prior
to enrollment

- Patients who are receiving any other investigational agents

- ECOG score greater than 1 (Karnofsky < 70%)

- HIV-positive patients

- Positive hepatitis C serology

- Inability to home monitor blood pressure

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements