ALT-803 Plus Nivolumab in Patients With Pretreated, Advanced or Metastatic Non-Small Cell Lung Cancer

NCT02523469 | Completed Phase 1 Results DMC

• 1 other identifier: 102323
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of the study is to define the safety and tolerability of this drug combination. The study will also define the response rate of patients with advanced and unresectable NSCLC.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Presence or Absence of a Dose Limiting Toxicity (DLT) of ALT-803 in Combination With Nivolumab

  A continual reassessment method (CRM) design will be used to identify the maximum tolerated dose (MTD) for Phase Ib patients

  Cycles 1-4: Weeks 1-6 of each cycle

• Objective Response Rate

  The phase II portion of the study looks to define the objective response rate (using immune-related RECIST) of ALT-803 added to nivolumab in patients with advanced and unresectable non-small cell lung cancer. Objective response rate will be defined by the best overall response, which is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease, the smallest measurements recorded since the treatment started). The subject's best response assignment will depend on the achievement of both measurement and confirmation criteria.

  While on study, at the end of each 6 week cycle; if off study, every 3 months, UP TO 3 YEARS

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  Up to 6 months

• Overall Survival (OS)

  From first dose until death or last known alive, up to 15 months.

• Duration of Response (DoR)

  Up to 6 months

Study Arms (8)

Cohort 1: ALT-803 6 µg/kg + Nivolumab 3 mg/kg

EXPERIMENTAL

Participants receive ALT-803 6 µg/kg + Nivolumab 3 mg/kg IV per protocol

Biological: ALT-803; Biological: Nivolumab

Cohort 2: ALT-803 10 µg/kg + Nivolumab 3 mg/kg

EXPERIMENTAL

Participants receive ALT-803 10 µg/kg + Nivolumab 3 mg/kg IV per protocol

Biological: ALT-803; Biological: Nivolumab

Cohort 3: ALT-803 15 µg/kg + Nivolumab 3 mg/kg

EXPERIMENTAL

Participants receive ALT-803 15 µg/kg + Nivolumab 3 mg/kg IV per protocol

Biological: ALT-803; Biological: Nivolumab

Cohort 4: ALT-803 20 µg/kg + Nivolumab 3 mg/kg (RP2D)

EXPERIMENTAL

Participants receive ALT-803 20 µg/kg + Nivolumab 3 mg/kg IV per protocol

Biological: ALT-803; Biological: Nivolumab

Arm A: RP2D ALT-803 + Nivolumab (Nivo-naïve)

EXPERIMENTAL

Participants receive ALT-803 20 µg/kg + Nivolumab 3 mg/kg IV; Nivolumab-naïve population

Biological: ALT-803; Biological: Nivolumab

Arm B: RP2D ALT-803 + Nivolumab (Nivo-progressor)

EXPERIMENTAL

Participants receive ALT-803 20 µg/kg + Nivolumab 3 mg/kg IV; prior Nivolumab exposure

Biological: ALT-803; Biological: Nivolumab

Exploratory Arm 1

NO INTERVENTION

ALT-803 ± Nivolumab for biomarker analysis only

Exploratory Arm 2

NO INTERVENTION

ALT-803 ± Nivolumab for biomarker analysis only

Interventions

ALT-803 BIOLOGICAL

ALT-803 administered IV at doses per arm (6, 10, 15, 20 µg/kg)

Arm A: RP2D ALT-803 + Nivolumab (Nivo-naïve); Arm B: RP2D ALT-803 + Nivolumab (Nivo-progressor); Cohort 1: ALT-803 6 µg/kg + Nivolumab 3 mg/kg; Cohort 2: ALT-803 10 µg/kg + Nivolumab 3 mg/kg; Cohort 3: ALT-803 15 µg/kg + Nivolumab 3 mg/kg; Cohort 4: ALT-803 20 µg/kg + Nivolumab 3 mg/kg (RP2D)

Nivolumab BIOLOGICAL

Nivolumab administered IV at 3 mg/kg per protocol

Also known as: OPDIVO

Arm A: RP2D ALT-803 + Nivolumab (Nivo-naïve); Arm B: RP2D ALT-803 + Nivolumab (Nivo-progressor); Cohort 1: ALT-803 6 µg/kg + Nivolumab 3 mg/kg; Cohort 2: ALT-803 10 µg/kg + Nivolumab 3 mg/kg; Cohort 3: ALT-803 15 µg/kg + Nivolumab 3 mg/kg; Cohort 4: ALT-803 20 µg/kg + Nivolumab 3 mg/kg (RP2D)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of NSCLC who present with Stage IIIB/Stage IV disease (according to version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology) or recurrent disease following radiation therapy or surgical resection.
• Patient must be eligible for treatment with nivolumab. Patients previously treated with nivolumab, pembrolizumab or atezolizumab, and who have progressed are eligible.
• Patients with targetable with EGFR or ALK mutations are eligible after disease recurrence or progression after at least one targeted therapy for advanced or metastatic disease.
• Measurable disease as defined by RECIST 1.1 criteria.
• Age ≥ 18 years
• Performance status: ECOG performance status of ≤1 (Appendix A)
• Adequate organ system function within 14 days of registration:
• ANC ≥ 750/μL (≥0.75 X 109/L) PLT ≥ 100,000/μL (≥ 30 X 109/L) HGB \> 8g/dL Total bilirubin \< 2.0 x ULN AST \< 3.0 X ULN ALT \< 3.0 X ULN eGFR\* \> 45mL/min
• \*using Cockcroft \& Gault equation (see Appendix B)
• Negative serum pregnancy test if WOCBP (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized).
• Female participants of childbearing potential must adhere to using a medically accepted method of birth control up to 28 days prior to screening and agree to continue its use during the study or be surgically sterilized (e.g., hysterectomy or tubal ligation) and males must agree to use barrier methods of birth control while on study. WOCBP must agree to use effective contraception during treatment and for at least 5 months following the last dose of study treatment.
• Prior to any study specific activities, the patient must be aware of the nature of his/her disease and willingly consent to the study after being informed of study procedures, the experimental therapy, possible alternatives, risks and potential benefits.

You may not qualify if:

• While prior therapy with nivolumab, pembrolizumab, or atezolizumab is allowed, any prior therapy with other anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) is not allowed.
• NYHA Class III or IV heart failure (Appendix C), uncontrollable supraventricular arrhythmias, any history of a ventricular arrhythmia, or other clinical signs of severe cardiac dysfunction.
• Symptomatic congestive heart failure, unstable angina pectoris, or myocardial infarction within 6 months of registration.
• Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval greater than 500 milliseconds).
• Patients with CNS metastases with the following exceptions: Patient untreated CNS metastases with 5 or fewer sites of disease, with no single site larger than 20mm, are eligible if they are asymptomatic and not requiring steroids at any dose. Patients with asymptomatic CNS metastases may be treated with radiosurgery before or during therapy on trial without treatment delays. Patients with treated, symptomatic CNS metastases are eligible if they are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to registration AND either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
• Known autoimmune disease requiring active treatment. Subjects with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of registration are excluded. Inhaled or topical steroids, and adrenal replacement steroid doses \< 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Subjects with a history of interstitial lung disease and/or pneumonitis.
• Known HIV-positive.
• Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.
• Positive hepatitis C serology or active hepatitis B infection. Chronic asymptomatic viral hepatitis is allowed.
• Women who are pregnant or nursing.
• Psychiatric illness/social situations that would limit compliance with study requirements.
• Any ongoing toxicity from prior anti-cancer treatment that, in the judgment of the investigator, may interfere with study treatment. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must resolve to grade 1 (NCI CTCAE version 4) or baseline prior to registration.
• Anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days of registration.
• Other illness that in the opinion of the investigator would exclude the patient from participating in this study, including uncontrolled diabetes mellitus, cardiac disease.

Sponsors & Collaborators

• Altor BioScience: collaborator
• Medical University of South Carolina: lead

Study Sites (4)

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• Wrangle JM, Velcheti V, Patel MR, Garrett-Mayer E, Hill EG, Ravenel JG, Miller JS, Farhad M, Anderton K, Lindsey K, Taffaro-Neskey M, Sherman C, Suriano S, Swiderska-Syn M, Sion A, Harris J, Edwards AR, Rytlewski JA, Sanders CM, Yusko EC, Robinson MD, Krieg C, Redmond WL, Egan JO, Rhode PR, Jeng EK, Rock AD, Wong HC, Rubinstein MP. ALT-803, an IL-15 superagonist, in combination with nivolumab in patients with metastatic non-small cell lung cancer: a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2018 May;19(5):694-704. doi: 10.1016/S1470-2045(18)30148-7. Epub 2018 Apr 5.

  PMID: 29628312 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

ALT-803; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The results should be interpreted with caution. Although 67 participants were enrolled, only 53 started treatment; this is explained in Pre-assignment Details. Exploratory arms were included in the protocol but had no participants assigned. Follow-up was limited for some participants, which may affect estimates for PFS, OS, and DoR. Analyses were descriptive and not adjusted for multiple comparisons. Missing data and early discontinuations may also impact results.

Results Point of Contact

• Title: Alan Brisendine, CCRP - Clinical Research Manager
• Organization: Medical University of South Carolina, Hollings Cancer Center

brisend@musc.edu

843-792-9007

Study Officials

• John Wrangle, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2015
• First Posted: August 14, 2015
• Study Start: January 8, 2016
• Primary Completion: February 24, 2023
• Study Completion: February 24, 2023
• Last Updated: February 17, 2026
• Results First Posted: February 17, 2026

Record last verified: 2026-01

Locations

US (4)