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

NCT ID: NCT01946789

Last Updated: 2025-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2017-12-31

Brief Summary

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

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.

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

N-803 IV 0.3/0.5 ug/kg

Group Type: EXPERIMENTAL

ALT-803

Intervention Type: BIOLOGICAL

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.

N-803 IV 1.0 ug/kg

Group Type: EXPERIMENTAL

ALT-803

Intervention Type: BIOLOGICAL

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.

N-803 IV 3.0 ug/kg

Group Type: EXPERIMENTAL

ALT-803

Intervention Type: BIOLOGICAL

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.

N-803 IV 6.0 ug/kg

Group Type: EXPERIMENTAL

ALT-803

Intervention Type: BIOLOGICAL

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.

N-803 Subcutaneous 6.0 ug/kg

Group Type: EXPERIMENTAL

ALT-803

Intervention Type: BIOLOGICAL

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.

N-803 Subcutaneous 10.0 ug/kg

Group Type: EXPERIMENTAL

ALT-803

Intervention Type: BIOLOGICAL

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.

N-803 Subcutaneous 15.0 ug/kg

Group Type: EXPERIMENTAL

ALT-803

Intervention Type: BIOLOGICAL

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.

N-803 Subcutaneous 20.0 ug/kg

Group Type: EXPERIMENTAL

ALT-803

Intervention Type: BIOLOGICAL

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.

N-803 Intratumoral 10.0 ug/kg followed by N-803 15.0 ug/kg subcutaneous

Group Type: EXPERIMENTAL

ALT-803

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Altor BioScience

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Ernstoff, MD

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

University of Minnesota

Minneapolis, Minnesota, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

University of Washington, Seattle Cancer Care Alliance

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/30045932/

Related Info

Other Identifiers

U01CA154967

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CITN06-ALT-803, QUILT-3.003

Identifier Type: -

Identifier Source: org_study_id