Details

Details

Title A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803, a Novel Recombinant IL-15 Complex in Patients with Advanced Solid Tumors: Melanoma, Renal Cell, Non-Small Cell Lung and Squamous Cell Head and Neck Cancer

IRB ALTR1614

CC 15-164

Hospital Main Campus

Stage N/A

Phase Phase 1

Disease Head and Neck, Lung - NSCLC (Non-small cell lung cancer), Melanoma, Renal

Drug ALT-803

Description

Description

Primary Objectives
  1. To study the safety of escalating doses of ALT-803 in patients with advanced solid tumors (melanoma, renal cell, non-small cell lung and squamous cell head and neck cancer) and screen the selected dose in an expanded cohort for evidence of antitumor activity
  2. To evaluate the effect of escalating doses of ALT-803 on the peripheral blood white blood cell (WBC) and absolute lymphocyte (ALC) counts
Secondary Objectives

To evaluate the effect of escalating doses of ALT-803 on:

  • The number and phenotype of peripheral blood mononuclear cells (PBMCs), including T and natural killer (NK) cells by multiparameter flow cytometry
  • The level of immune response to autochthonous viral and tumor antigens by interferongamma (IFN-γ) ELISPOT
  • Immunogenicity and pharmacokinetics of ALT-803
  • Overall objective response rate (ORR) and response duration

Inclusion Criteria

Inclusion Criteria

  1. Patients must have 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. The primary site may be cutaneous or unknown, but mucosal and ocular primaries are excluded. NOTE: 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.li>
  2. Prior therapy requirements:
    • At least one prior therapy using an agent with the potential for prolonged remission (generally includes interleukin-2, checkpoint-blocking antibodies, or adoptive cell therapy)
    • At least 4 weeks from last dose of prior chemotherapy or immunomodulator therapy with resolution of the acute toxicities. For patients coming off molecularly-targeted therapy, at least 2 weeks since last dose and recovery from laboratory and constitutional toxicities. Patients must meet entry eligibility criteria.
    • At least 2 weeks from completion of prior radiation therapy with no residual radiation 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

    NOTE: Any patient whose tumors carry a BRAF v600 mutation should either be excluded, or may be included after experiencing progression following treatment with BRAF inhibitor regimen or if they consent and agree to forgo FDA-approved therapies that increase median survival.

  3. Age >18 years at the time of consent. Because no dosing or adverse event (AE) data are currently available on the use of ALT-803 in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
  4. ECOG performance status ≤1 (Karnofsky ≥70%, see Appendix A).
  5. Both men and women of all races and ethnic groups are eligible for this trial
  6. Life expectancy of greater than 6 months
  7. Patients must have normal organ and marrow function as defined below:
    • leukocytes ≥3,000/mcL
    • absolute lymphocytes count ≥500/mcL
    • absolute neutrophil count ≥1,000/mcL (without hematopoietic growth factors)
    • platelets ≥100,000/mcL (without transfusion)
    • hemoglobin ≥10 g/dL (may be transfused but must be stable without clinical evidence of ongoing blood loss or hemolysis)
    • total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT) ≤2.5 x institutional upper limit of normal
    • Creatinine within normal institutional limits OR
    • Creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
  8. 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.
  9. The effects of ALT-803 on the developing human fetus are unknown. Thus, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) before study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception before the study, for the duration of study participation, and 4 months after the completion of ALT-803 administration.
  10. Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria

Exclusion Criteria

  1. 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. NOTE: Patients with chronic residual prior therapy-related toxicity (e.g. vitiligo, alopecia, low grade neuropathy), or in the consensus opinion of the CITN/CTEP investigators would not impact the safety of the patient or the integrity of the study, are not excluded. NOTE: 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.
  2. Patients who are receiving any other investigational agents.
  3. Patients with known brain metastases should be excluded from this clinical trial because IL-15 might induce substantial swelling of intracranial lesions, their general poor prognosis, and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Previously treated brain metastases, neurologically stable, and no ongoing or anticipated need for steroid therapy are eligible.
  4. Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant lung disease or psychiatric illness/social situations that would limit compliance with study requirements. Patient who, in the clinical judgment of the investigator, 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.
  5. Patients with thyroid disease should be excluded unless euthyroid on suppressive or replacement therapy.
  6. Pregnant women are excluded from this study because ALT-803 is an anticancer immunotherapeutic agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ALT-803, breastfeeding should be discontinued if the mother is treated with ALT-803. These potential risks may also apply to other agents used in this study.
  7. HIV-positive patients, because the effect of IL-15 on viral loads, HIV immunity, and infectivity of proliferating T cells is unknown and a separate question.
  8. Positive hepatitis C serology or active hepatitis B infection, because of the risk of hepatic inflammation and the possible confounding of the assessment of drug toxicity.
  9. Active bacterial or fungal infection. All prior infections must be resolved following optimal therapy.
  10. Chronic systemic or regular inhaled corticosteroid use within 7 days prior to initiation of protocol therapy.
  11. Immunosuppressive therapy within 30 days prior to initiation of protocol therapy.
  12. Inability to home monitor blood pressure.
  13. 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 (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmias requiring chronic therapy).