A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803 in Patients With Advanced Solid Tumors

This trial will investigate the safety and immunogenicity, immunomodulatory properties, and
clinical benefits of treatment with weekly doses of ALT-803 in patients with advanced solid
tumors.

ENTRY CRITERIA:

DISEASE CHARACTERISTICS:

- Histological or cytological confirmed malignancy in the following disease groups:
melanoma that is metastatic or unresectable, non-small cell lung carcinoma, renal cell
carcinoma or squamous cell head and neck carcinoma, for which standard curative or
palliative measures do not exist or are no longer effective.

- Primary site may be cutaneous or unknown, but mucosal and ocular primaries are
excluded.

- Patients with non-small lung cancer must have had prior EGFR and ALK testing. Patients
with sensitizing mutations in EGFR or ALK rearrangements should have been treated with
prior targeted agents and have had progression or discontinued due to toxicity from
these agents.

- No patients with known brain metastases.

PRIOR/CONCURRENT THERAPY:

- At least one prior therapy using an agent with the potential for prolonged remission.

- Patients with BRAF v600 mutation should be excluded or may be included after
experiencing progression following treatment with BRAF inhibitor regimen or if they
consent to forgo FDA-approved therapies that increase median survival.

- At least 4 weeks from last dose of prior chemotherapy or immunomodulator therapy with
full recovery of acute toxicities. For patients coming off molecularly-targeted
therapy, at least 2 weeks since last dose and recovery from laboratory and
constitutional toxicities.

- At least 2 weeks from completion of prior radiation therapy with full recovery from
toxicities.

- At least 4 weeks from last dose of prior investigational therapy with recovery to meet
baseline eligibility criteria.

- Not receiving any current anticancer therapy

- No patients who have had chemotherapy, targeted therapy, or radiotherapy and have not
recovered from acute toxicity to their pretreatment baseline or to a grade 1 level
within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
For resolution of autoimmune toxicity from prior immune therapy, patients must be off
steroids for at least 30 days without relapse of autoimmune toxicity, or it must be at
least 30 days from their last dose of infliximab or related immunosuppressive therapy
without relapse of autoimmune toxicity.

- No patients who are receiving any other investigational agents.

- No patients who are receiving chronic systemic or regular inhaled corticosteroid use
within 7 days prior to initiation of protocol therapy.

- No immunosuppressive therapy within 30 days prior to treatment start.

PATIENT CHARACTERISTICS

- Age >18 years

- Both men and women of all races and ethnic groups are eligible.

Performance Status

- ECOG performance status ≤1

- Life expectancy of greater than 6 months.

Bone Marrow Function

- leukocytes ≥3,000/mcL

- absolute lymphocyte count ≥500/mcL

- absolute neutrophil count ≥1,000/mcL (without hematopoietic growth factors)

- platelets ≥100,000/mcL (without transfusion)

- hemoglobin ≥ 10 gm/dL (may be transfused but must be stable without clinical evidence
of ongoing blood loss or hemolysis)

Hepatic Function

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

Kidney Function

- Creatinine within normal institutional limits OR

- Creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above
institutional normal.

Pulmonary Function

• No history of severe COPD or emphysema or interstitial lung disease currently on home
supplemental oxygen. Patients with NSCLC with stable COPD or emphysema not requiring
supplemental oxygen are eligible.

Cardiac Function

- No symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.
Patients who have underlying risk factors for cardiac disease should be excluded or
undergo clearance stress-based cardiac function testing. The pre-treatment QTc must be
<500 msec.

- No class II or greater congestive heart failure as described in the New York Heart
Association Functional Classification criteria or serious arrhythmias likely to
increase the risk of cardiac complications of cytokine therapy.

Other

- Women of child-bearing potential and men must agree to use adequate contraception.

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

- No uncontrolled inter-current illness or psychiatric illness/social situations that
would limit compliance with study requirements.

- No pregnant women.

- No HIV-positive patients.

- No positive hepatitis C serology or active hepatitis B infection.

- No active bacterial or fungal infection.

- No inability to home monitor blood pressure.

- Patients with thyroid disease should be excluded unless euthyroid on suppressive or
replacement therapy.