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

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

The proposed clinical trial is a phase I, open-label, multi-center, dose-escalation study of ALT-803 in patients with surgically incurable advanced solid tumors: melanoma, renal cell, non-small cell lung and squamous cell head and neck cancer

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Biological: ALT-803

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington, Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N-803 IV 0.3/0.5 ug/kg	Biological: ALT-803; N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
Experimental: N-803 IV 1.0 ug/kg	Biological: ALT-803; N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
Experimental: N-803 IV 3.0 ug/kg	Biological: ALT-803; N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
Experimental: N-803 IV 6.0 ug/kg	Biological: ALT-803; N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
Experimental: N-803 Subcutaneous 6.0 ug/kg	Biological: ALT-803; N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
Experimental: N-803 Subcutaneous 10.0 ug/kg	Biological: ALT-803; N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
Experimental: N-803 Subcutaneous 15.0 ug/kg	Biological: ALT-803; N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
Experimental: N-803 Subcutaneous 20.0 ug/kg	Biological: ALT-803; N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
Experimental: N-803 Intratumoral 10.0 ug/kg followed by N-803 15.0 ug/kg subcutaneous	Biological: ALT-803; N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity	The safety endpoint is the MTD of ALT-803, defined as the dose level below that at which ≥2 of 6 patients experience a DLT.	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Developed Anti-drug Antibodies to ALT-803	Immunogenicity of ALT-803 assessed by ELISA	14 days post final dose, up to 135 days
To Evaluate the Effect of Escalating Doses of ALT-803: Pharmacokinetics (Half Life and Tmax)	Pharmacokinetics of ALT-803 assessed by ELISA	24 hours post dose
To Evaluate the Effect of Escalating Doses of ALT-803: Pharmacokinetics (Cmax)	Pharmacokinetics of ALT-803 assessed by ELISA	24 hours after first dose
To Evaluate the Effect of Escalating Doses of ALT-803: Pharmacokinetics (AUC 0-t, AUC0-24, AUC0-infinity)	Pharmacokinetics of ALT-803 assessed by ELISA	24 hours after first dose
To Evaluate the Effect of Escalating Doses of ALT-803: Interferon Gamma (IFN-γ)	The level of immune response to autochthonous viral and tumor antigens by interferon gamma (IFN-γ) ELISPOT	Cycle 1 Week 1, pre-dose; Cycle 1 Week 1, 30 minutes post dose; Cycle 1 Week 1, 2 hours post dose; Cycle 1 Week 1, 4 hours post dose; Cycle 1 Week 1, 8 hours post dose; Cycle 1 Week 1, 24 hours post dose
Objective Response Rate	Number of patients with CR, PR, SD, and PD	Up to 6 months

Collaborators and Investigators

• Sponsor: Altor BioScience
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Marc Ernstoff, MD, Roswell Park Cancer Institute

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: September 11, 2013
• First Submitted That Met QC Criteria: September 17, 2013
• First Posted (Estimated): September 20, 2013

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 20, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: cancer; solid tumors; metastatic; melanoma; IL-15; unresectable; renal cell; non-small cell lung; squamous cell head and neck
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CITN06-ALT-803, QUILT-3.003; U01CA154967 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED