Interleukin-2 Plus Monoclonal Antibody Therapy in Treating Patients With Solid Tumors

OBJECTIVES: I. Determine the toxic effects of humanized anti-HER2 monoclonal antibodies when
administered in combination with interleukin-2 (IL-2) in patients with solid tumors. II.
Measure in vitro cytotoxicity using peripheral blood mononuclear cells, plasma, and target
cell lines that express HER2 in this patient population. III. Phenotypically characterize
effector cells at the time of antibody administration and 24 hours after three days of
intermediate dose IL-2 pulsing in these patients. IV. Measure antitumor response in these
patients.

OUTLINE: Cohorts of 6 patients are enrolled at 4 antibody dose levels. After at least 6
patients have been treated on study for at least 30 days, the next dose level may be
initiated provided that fewer than 2 of the first 6 evaluable patients experience dose
limiting toxicity (DLT) related to either the antibody or the combination of antibody with
interleukin-2 (IL-2). If 2 or more patients experience DLT, the next cohort is enrolled at
the antibody dose midway between the current and previous dose levels. An additional 6
patients are entered at the maximum tolerated dose. On course 1, patients receive IL-2
subcutaneously (SQ) daily on days 1-7 and humanized anti-HER-2 monoclonal antibodies IV over
90 minutes on day 7. Patients receive intermediate dose pulsed IL-2 SQ on days 8-10 and low
dose IL-2 SQ on days 11-20. On course 2 and all subsequent courses, patients receive
humanized anti-HER2 monoclonal antibodies IV immediately prior to IL-2 (SQ) on day 1 and
intermediate dose pulsed IL-2 (SQ) on days 1-3. Patients receive low dose IL-2 (SQ) on days
4-14. Treatment may be delayed up to 7 days to allow for recovery and for tumor restaging,
but daily low dose IL-2 is continued in this interval. Patients are followed at 4 weeks and
then every 8 weeks until progression or death.

PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS: Histologically confirmed nonhematologic malignancy Refractory
disease or disease for which no effective standard therapy exists HER2 overexpression in
tumor tissue Measurable or evaluable disease No CNS metastases Hormone receptor status:
Not specified

PATIENT CHARACTERISTICS: Age: 18 and over Menopausal status: Not specified Performance
status: CALGB 0-1 Life expectancy: At least 3 months Hematopoietic: Absolute granulocyte
count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater
than 1.5 times normal SGOT no greater than 5 times normal Alkaline phosphatase no greater
than 5 times normal Renal: BUN no greater than 1.5 times normal Creatinine no greater than
1.5 times normal Cardiovascular: No uncontrolled or severe cardiac disease LVEF at least
45% by MUGA or echocardiogram Other: HIV negative No immunologic disease (e.g., autoimmune
disease) Negative viral hepatitis antibodies No psychiatric conditions which would prevent
compliance with treatment Not pregnant or nursing Fertile patients must use effective
contraception No active uncontrolled bacterial, viral, or fungal infection Prior or
concurrent malignancy allowed

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior interleukin-2 (IL-2) and/or herceptin
allowed No concurrent immunosuppressive drugs or other immunomodulators (other than IL-2)
Chemotherapy: At least 6 weeks since nitrosoureas, melphalan, or mitomycin More than 4
weeks since other chemotherapy Endocrine therapy: No concurrent corticosteroids
Radiotherapy: More than 4 weeks since prior radiotherapy Surgery: At least 4 weeks since
major surgery