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QUILT-2.023: A Study of ALT-803, a Fusion Protein Activator of Natural Killer and T-Cells, in Combination With Pembrolizumab vs Pembrolizumab Alone as First-Line Treatment for Patients With Metastatic NSCLC.

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ClinicalTrials.gov Identifier: NCT03520686
Recruitment Status : Recruiting
First Posted : May 10, 2018
Last Update Posted : November 21, 2018
Sponsor:
Collaborator:
NantCell, Inc.
Information provided by (Responsible Party):
Altor BioScience

Brief Summary:
This is a phase 2, open-label, randomized study to compare the safety and efficacy of combination therapy with ALT-803 and pembrolizumab (experimental arm) versus pembrolizumab alone (control arm), as first-line treatment for subjects with metastatic NSCLC in which pembrolizumab is indicated for first-line treatment.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Drug: ALT-803 + Pembrolizumab Drug: Pembrolizumab Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 388 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Randomized Study of ALT-803, a Fusion Protein Activator of Natural Killer and T-Cells, in Combination With Pembrolizumab vs Pembrolizumab Alone as First-Line Treatment for Patients With Metastatic NSCLC.
Actual Study Start Date : May 18, 2018
Estimated Primary Completion Date : April 18, 2021
Estimated Study Completion Date : April 18, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A Drug: ALT-803 + Pembrolizumab

The treatment plan in the experimental arm will consist of repeated 3-week cycles for a maximum treatment period of 2 years, in accordance with the following dosing regimen:

Day 1, every 3 weeks:

  • Pembrolizumab (200 mg intravenous infusion [IV])
  • ALT-803 (15 μg/kg subcutaneously [SC])

Active Comparator: Group B Drug: Pembrolizumab

The reference treatment will consist of repeated 3-week cycles for a maximum treatment period of 2 years, in accordance with the following dosing regimen:

Day 1, every 3 weeks:

• Pembrolizumab (200 mg IV)





Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 24 Months ]
    Defined by RECIST Version 1.1 based on BICR


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 24 Months ]
    Defined by RECIST Version 1.1 based on BICR

  2. Overall Survival (OS) [ Time Frame: 24 Months ]
  3. Duration of Response (DOR) [ Time Frame: 24 Months ]
    Defined by RECIST Version 1.1 based on BICR.

  4. Disease-specific survival (DSS) [ Time Frame: 24 Months ]
  5. Disease Control Rate (DCR) [ Time Frame: 2 Months ]
    Confirmed CR, PR, or SD lasting for at least 2 months by RECIST Version 1.1 based on BICR

  6. PFS [ Time Frame: 24 Months ]
    Defined by irRC based on BICR.

  7. Overall Response Rate (ORR) [ Time Frame: 24 Months ]
    Defined by irRC based on BICR.

  8. Duration of Response (DOR) [ Time Frame: 24 Months ]
    Defined by irRC based on BICR.


Other Outcome Measures:
  1. Incidence of treatment-emergent AEs and SAEs [ Time Frame: 24 Months ]
    Graded using the NCI CTCAE Version 4.03

  2. Serum concentration of ALT-803 [ Time Frame: 24 Months ]
    maximum observed concentration (Cmax)

  3. Immunogenicity profile of ALT-803 in combination with pembrolizumab. [ Time Frame: 24 Months ]
    Detection of anti-drug antibodies

  4. Tumor molecular profiles and correlations with subject outcomes [ Time Frame: 9 Weeks ]
    Genomic sequencing of tumor cells from tissue

  5. Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. [ Time Frame: 24 Months ]
    Expression levels of specific tumor- and immune-related analytes in ctDNA and ctRNA will be measured by qPCR



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years old.
  2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
  3. Histologically-confirmed stage 4 NSCLC that: has not been treated with prior chemotherapy for metastatic disease and has high PD-L1 expression (ie, a TPS ≥ 50%), as determined by an FDA-approved test. Previous neoadjuvant/adjuvant chemotherapy is allowed if completed ≥ 6 months before diagnosis of metastatic disease.The subject's tumor must not harbor an EGFR sensitizing (activating) mutation or ALK translocation. EGFR sensitizing mutations are those mutations that are amenable to treatment with tyrosine kinase inhibitors including erlotinib, gefitinib, or afatinib. Investigators must be able to produce the source documentation of the EGFR mutation and ALK translocation status in all subjects with non-squamous histologies AND for subjects in whom testing is clinically recommended. If either an EGFR sensitizing mutation of ALK translocation is detected, additional information regarding the mutation status of the other molecule is not required. If unable to test for these molecular changes, formalin fixed paraffin embedded tumor tissue of any age should be submitted to a central laboratory designated by the Sponsor for such testing. Subjects with non-squamous histologies will not be randomized until the EGFR mutation status and/or ALK translocation status is available in source documentation at the site. For patients enrolled who are known to have a tumor of predominantly squamous histology, molecular testing for EGFR and ALK translocation will not be required as this is not standard of care and is not part of current diagnostic guidelines.
  4. Life expectancy of ≥ 3 months.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  6. Have at least 1 measurable lesion of ≥ 1.0 cm. Confidential and Proprietary 6 ALT-803 and Pembrolizumab for NSCLC Altor BioScience Clinical Trial Protocol: QUILT-2.023
  7. Must be willing to release tumor biopsy specimen used for diagnosis of metastatic NSCLC (if available) for additional exploratory tumor molecular profiling.
  8. Must be willing to provide blood samples prior to the start of treatment on this study for exploratory tumor molecular profiling analyses.
  9. Must be willing to provide a tumor biopsy specimen 9 weeks after the start of treatment for exploratory analyses, if considered safe by the Investigator.
  10. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
  11. Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 1 year after completion of therapy, and non-sterile male subjects must agree to use a condom for up to 4 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and abstinence.

Exclusion Criteria:

  1. Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the subject at high risk for treatment-related complications.
  2. A history of prior malignancy. Subjects with a history of basal or squamous cell carcinoma of the skin, superficial bladder cancer, or in situ cervical cancer, or those that have received curative therapy with no disease recurrence for ≥ 5 years, may be enrolled.
  3. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma).
  4. History of organ transplant requiring immunosuppression; or history of pneumonitis or interstitial lung disease requiring treatment with systemic steroids; or a history of receiving systemic steroid therapy or any other immunosuppressive medication ≤ 3 days prior to study initiation. Daily steroid replacement therapy (eg, prednisone or hydrocortisone) and corticosteroid use to manage AEs are permitted.
  5. Prior systemic chemotherapy, major surgery, or thoracic radiation within 3 weeks of study initiation.
  6. Requirement for other forms of anticancer treatment while on trial, including maintenance therapy, other radiation therapy, and/or surgery.
  7. Known CNS metastases or carcinomatous meningitis. Subjects with previously treated, stable CNS metastases (no evidence of progression for ≥ 4 weeks, and resolution of neurologic symptoms to baseline state) are permitted in this study.
  8. History of receiving a live vaccine 30 days prior to study treatment.
  9. History of human immunodeficiency virus (HIV), or known active hepatitis B or C infection.
  10. An active infection requiring systemic IV therapy.
  11. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
  12. Inadequate organ function, evidenced by the following laboratory results:

    1. Absolute neutrophil count < 1,500 cells/mm3.
    2. Platelet count < 100,000 cells/mm3.
    3. Total bilirubin greater the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
    4. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 1.5 × ULN.
    5. Alkaline phosphatase (ALP) levels > 2.5 × ULN.
    6. Serum creatinine > 2.0 mg/dL or 177 μmol/L or creatinine clearance < 40 mL/min (using the Cockcroft-Gault formula)
  13. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication. Subjects with uncontrolled hypertension should be medically managed on a stable regimen to control hypertension prior to study entry.
  14. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
  15. Known hypersensitivity to any component of the study medication(s).
  16. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
  17. Participation in an investigational drug study or history of receiving any investigational treatment within 30 days prior to screening for this study, except for testosterone-lowering therapy in men with prostate cancer.
  18. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
  19. Concurrent participation in any interventional clinical trial.
  20. Pregnant and nursing women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03520686


Contacts
Contact: Liza Hernandez, BS 954-433-8600 ext 879 lizahernandez@altorbioscence.com
Contact: Kyle Conradi, BS 954-433-8600 ext 812 kyleconradi@altorbioscience.com

Locations
United States, Alaska
Alaska Urological Institute - Alaska Clinical Research Center Recruiting
Anchorage, Alaska, United States, 99503
Contact: Ashli Meek       Ameed@akmed.com   
Principal Investigator: Musaberk Goksel, MD         
United States, California
Chan Soon-Shiong Institute for Medicine Recruiting
El Segundo, California, United States, 90245
Contact: Jessica Daly       Jessica.Daly@cssifm.org   
Principal Investigator: Mira Kistler, MD         
United States, Missouri
Mercy Research Joplin Recruiting
Joplin, Missouri, United States, 64804
Contact: Esmeralda Carrillo       Esmeralda.Carrillo@mercy.net   
Principal Investigator: Samir M Dalia, MD         
Mercy Clinic Cancer & Hematology - Chub O'Reilly Cancer Center Recruiting
Springfield, Missouri, United States, 65804
Contact: Pearlena Hamlet       pearlena.hamlet@mercy.net   
Principal Investigator: Mohan Tummala, MD         
United States, South Carolina
Medical University of South Carolina (MUSC) - Hollings Cancer Center (HCC) Recruiting
Charleston, South Carolina, United States, 29425
Contact: Eleanor Hardy       hardyel@musc.edu   
Principal Investigator: John Wrangle, MD.         
Saint Francis Cancer Center/Con Secours St. Francis Health System Recruiting
Greenville, South Carolina, United States, 29607
Contact: Melissa Beckman       melissa_beckman@bshsi.org   
Principal Investigator: Robert Siegel, MD.         
Sponsors and Collaborators
Altor BioScience
NantCell, Inc.

Responsible Party: Altor BioScience
ClinicalTrials.gov Identifier: NCT03520686     History of Changes
Other Study ID Numbers: QUILT-2.023
First Posted: May 10, 2018    Key Record Dates
Last Update Posted: November 21, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Altor BioScience:
Pembrolizumab
ALT-803
Non-Small Cell Lung Cancer
Immunotherapy

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pembrolizumab
Antineoplastic Agents