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Phase I Study of ALT-801 in Patients With Progressive Metastatic Malignancies

Phase 1
18 Years
Not Enrolling
Progressive Metastatic Malignancies

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Trial Information

Phase I Study of ALT-801 in Patients With Progressive Metastatic Malignancies

Most current cancer treatment strategies involve the use of chemotherapeutic or biological
drugs that exhibit variable efficacy and considerable toxicity. The limitations are often
the result of the adverse side effects of the therapeutic drug on normal tissues. One
approach to control these effects is to target the therapy to the tumor site. Of the
identified tumor antigens, the human p53 tumor suppressor protein is overexpressed in a wide
range of human malignancies. p53 is an intracellular tumor suppressor protein that acts to
arrest the proliferation of cells. When mutated, it loses its ability to suppress abnormal
proliferation and exhibits a longer half-life than the wild-type protein, allowing for its
accumulation in tumors. In addition, p53 overexpression correlates with tumor transformation
and aggression and is associated with lower overall survival rates and resistance to
chemotherapeutic intervention in cancer patients. Therefore, p53 appears to be a marker for
a considerable number of human malignancies and represents a good target for
immunotherapeutics. However, p53 cannot be used as a target for antibodies because it is
not displayed independently on the cell surface. Instead, the p53 protein is processed
intracellularly into peptide fragments that are then displayed on the cell surface in the
context of MHC. These peptide/MHC complexes are recognized by T-cells via their T-cell
receptors (TCRs). Recently it has been confirmed that the peptide fragment is significantly
elevated in a wide range of human tumor tissues, particularly in melanoma, renal, lung,
breast, colorectal, bladder, ovary, stomach, esophagus, lymphoma, liver, leukemia, and head
& neck cancer. Targeted approaches to concentrate therapeutic cytokines at the tumor sites
that express p53 could provide considerable advantages over current treatment.

Interleukin-2 (IL-2) is a well-characterized growth factor for immune effector cells which
play critical roles in tumor control and rejection. A recombinant human IL-2 has been
approved for treating metastatic melanoma and renal cell carcinoma. However, the major
drawback of IL-2 therapy is its severe systemic toxicity. As a result, use of high dose IL-2
is limited to specialized programs with experienced personnel and it is generally offered to
patients who are responsive and have excellent organ function. Thus, there is a critical
need for innovative strategies that enhance the effects of IL-2 or reduce its toxicity
without compromising clinical benefits.

The study drug, ALT-801, is a biologic compound composed of interleukin-2 (IL-2) genetically
fused to a humanized soluble T-cell receptor directed against the p53-derived antigen. This
study is to evaluate whether directing IL-2 activity using ALT-801 to the patient's tumor
sites that overexpress p53 results in clinical benefits.

The study drug will be administered by bolus intravenous infusion in an in-patient hospital
setting under the supervision of a qualified physician experienced in the use of anti-cancer
agents including high dose IL-2. An intensive care facility and specialists skilled in
cardiopulmonary or intensive care medicine must be available. There are two treatment
cycles. For each treatment cycle, patients will be admitted to the hospital, remain in the
hospital during the study drug infusion period, and be discharged from the hospital the day
after the last infusion at the Principal Investigator's discretion. There is a 10-day
resting period between the treatment cycles. Tumor assessments will be done at weeks 7 and
11 after starting the study drug.

Inclusion Criteria



- Locally advanced or metastatic malignancies

- Histologically or cytologically confirmed

- Evaluable

- Surgically and medically incurable

- Not responding to standard therapy or no other standard therapy exists

- HLA-A2.1/p53 positive


- No prior Proleukin therapy within one year

- No concurrent radiotherapy, chemotherapy, or other immunotherapy

- More than 4 weeks since prior major radiotherapy

- More than 4 weeks since prior cytotoxic therapy

- More than 6 weeks since prior nitrosoureas therapy

- More than 8 weeks since prior monoclonal antibody therapy


Life expectancy

- > 3 months

Performance status

- ECOG 0 or 1

Bone marrow reserve

- Absolute neutrophil count (AGC/ANC) ≥ 1,500/uL

- Platelets ≥100,000/uL

- Hemoglobin ≥ 10g/dL

Renal function

- Serum creatinine ≤ 1.5 X ULN

Hepatic function

- Total bilirubin ≤ 1.5 X ULN

- AST ≤ 2.5 X ULN

- Alkaline phosphatase ≤ 2.5 X ULN

- PT INR ≤ 1.5 X ULN

- aPTT ≤ 1.5 X ULN


- May be safely tapered off anti-hypertensives if currently on anti-hypertensives

- New York Heart Association classification I or II

- No congestive heart failure <6 months

- No unstable angina pectoris <6 months

- No myocardial infarction <6 months

- No history of ventricular arrhythmias

- Normal cardiac stress test required if any of the following is present:

- Over age 50

- History of abnormal EKG

- Symptoms of cardiac ischemia or arrhythmia


- Normal pulmonary function test (FEV1 ≥ 75% of predicted value) if any of the
following is present:

- Prolonged history of cigarette smoking

- Symptoms of respiratory dysfunction


- No known autoimmune disease

- No known HIV positive

- No psychiatric illness/social situations that would limit study compliance

- No history or evidence of CNS disease

- No active systemic infection requiring parental antibiotic therapy

- No systemic steroid therapy required

- No prior organ allograft

- Not receiving other investigational agents

- Not receiving chronic medication for asthma

- Not pregnant or nursing

- Fertile patients must use effective contraception

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate the safety and toxicity of ALT-801 in patients with progressive metastatic malignancies.

Outcome Time Frame:

18 months

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

May 2007

Completion Date:

October 2009

Related Keywords:

  • Progressive Metastatic Malignancies
  • cancer
  • p53
  • immunotherapy
  • targeted
  • metastatic
  • malignancy
  • malignancies
  • interleukin-2
  • IL-2
  • fusion protein
  • antitumor
  • melanoma
  • renal cancer
  • lung cancer
  • kidney cancer
  • breast cancer
  • colorectal cancer
  • colon cancer
  • renal cell carcinoma
  • advanced cancer
  • head and neck cancer
  • breast tumors
  • cancer of head and neck
  • esophagus cancer
  • lymphoma
  • ovarian cancer
  • ovary cancer
  • bladder cancer
  • stomach cancer
  • TCR
  • T-cell receptor
  • P53 gene
  • p53 tumor suppressor protein
  • Neoplasms



MD Anderson Cancer Center Orlando Orlando, Florida  32806
H. Lee Moffitt Cancer Center & Research Institute Tampa, Florida  33612
University of Colorado, Anschutz Cancer Pavillion Aurora, Colorado  80010
University of Washington, Seattle Cancer Care Center Seattle, Washington  98109