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QUILT 2.023: A Study of N803 in Combination With Pembrolizumab vs Pembrolizumab Alone as First-Line Treatment for Patients With Stage 3 or 4 NSCLC.

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ClinicalTrials.gov Identifier: NCT03520686
Recruitment Status : Recruiting
First Posted : May 10, 2018
Last Update Posted : October 11, 2019
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 N-803 and pembrolizumab (experimental arm) versus pembrolizumab alone (control arm), as first-line treatment for subjects with stage 3 or 4 advanced or metastatic NSCLC in which pembrolizumab is indicated for first-line treatment.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 388 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: QUILT 2.023: A Phase 2, Open-Label, Randomized Study of N803, a Fusion Protein Activator of Natural Killer and T-Cells, in Combination With Pembrolizumab vs Pembrolizumab Alone as First-Line Treatment for Patients With Advanced or 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: N-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])
  • N-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 iRECIST based on BICR.

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

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


Other Outcome Measures:
  1. Incidence of treatment-emergent AEs and SAEs [ Time Frame: 24 Months ]
    Graded using the NCI CTCAE Version 5.0

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

  3. Immunogenicity profile of N-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



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 3 or 4 NSCLC disease. Subjects with stage 3 disease must not be candidates for treatment with surgical resection or chemoradiation.
  4. Subjects must not have received prior systemic chemotherapy for advanced or metastatic NSCLC. Previous neoadjuvant/adjuvant chemotherapy is allowed if completed ≥ 6 months before diagnosis of metastatic disease.
  5. NSCLC tumors must have PD-L1 expression (i.e. a TPS ≥1%) as determined by an FDA-approved test.
  6. 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.
  7. Life expectancy of ≥ 3 months.
  8. ECOG performance status of 0 or 1.
  9. Measurable tumor lesions according to RECIST 1.1.
  10. 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. Must be willing to release tumor biopsy specimen used for diagnosis of metastatic NSCLC (if available) for additional exploratory tumor molecular profiling.

11. Must be willing to provide blood samples prior to the start of treatment on this study for exploratory research.

12. 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.

13. Ability to attend required study visits and return for adequate follow-up, as required by this protocol 14. 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), hormonal therapy, 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. Tumors that harbor an EGFR sensitizing (activating) mutation or ALK translocation.
  3. 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.
  4. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma).
  5. 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.
  6. Prior systemic chemotherapy, major surgery, or thoracic radiation within 3 weeks of study initiation.
  7. Requirement for other forms of anticancer treatment while on trial, including maintenance therapy, other radiation therapy, and/or surgery.
  8. 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.
  9. History of receiving a live vaccine 30 days prior to study treatment.
  10. History of human immunodeficiency virus (HIV), or known active hepatitis B or C infection.
  11. An active infection requiring systemic IV therapy.
  12. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
  13. 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)
  14. 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.
  15. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
  16. Known hypersensitivity to any component of the study medication(s).
  17. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
  18. 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.
  19. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
  20. Concurrent participation in any interventional clinical trial.
  21. 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
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Contact: Ann Vollmer, BA 310-882-3202 ann.vollmer@nantkwest.com
Contact: Dea Hamilton, BSN 919-583-6767 dea.hamilton@nantkwest.com

Locations
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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: Clinical Trials Navigator       patients@cssifm.org   
Principal Investigator: Mira Kistler, MD         
Adventist Health Glendale Recruiting
Glendale, California, United States, 92106
Contact: Javier Valeriano    818-409-8009    javier.valeriano@ah.org   
Principal Investigator: Mihran Shirinian, MD         
United States, Florida
Baptist Health South Florida - Miami Cancer Institute Recruiting
Miami, Florida, United States, 33176
Contact: Winston Dukes    614-668-8279    moraced@baptisthealth.net   
Principal Investigator: Miguel A Villalona Calero, MD         
United States, Illinois
Healthcare Research Network Recruiting
Tinley Park, Illinois, United States, 60487
Contact: Brian Springer    708-745-9971    bspringer@healthcareresearchnetwork.com   
Principal Investigator: Suby Rao, MD         
United States, Kentucky
Baptist Health - Lexington Recruiting
Lexington, Kentucky, United States, 40503
Contact: Cortney Grimes    502-721-6012    cortney.grimes@bhsi.com   
Principal Investigator: Firas Badin, MD         
Baptist Health Louisville Recruiting
Louisville, Kentucky, United States, 40503
Contact: Cortney Grimes    859-260-6295    cortney.grimes@bhsi.com   
Principal Investigator: Wangjian Zhong, 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, Montana
St. Vincent Frontier Cancer Center Recruiting
Billings, Montana, United States, 59102
Contact: Sabrina Leonhardt    406-238-6290    sabrina.leonhardt@sclhealth.org   
Contact: Kailey Prokop    406-238-6290    kailey.prokop@sclhealth.org   
Principal Investigator: Patrick W Cobb, MD         
United States, Oklahoma
Mercy Research Oklahoma City Recruiting
Oklahoma City, Oklahoma, United States, 73120
Contact: Sheryl Freeland, RN    405-752-3402    sheryl.freeland@mercy.net   
Principal Investigator: Carla Kurkjian, MD         
United States, Pennsylvania
LeHigh Valley Recruiting
Allentown, Pennsylvania, United States, 18103
Contact: Alexandra Bauman    610-402-9543    alexandra_L.Baumann@lvhn.org   
Principal Investigator: Brian Patson, MD         
United States, South Carolina
Medical University of South Carolina (MUSC) - Hollings Cancer Center (HCC) Recruiting
Charleston, South Carolina, United States, 29425
Contact: Alexandra Leitner, MPH       leitnera@musc.edu   
Principal Investigator: John Wrangle, MD.         
Saint Francis Cancer Center/Bon Secours St. Francis Health System Recruiting
Greenville, South Carolina, United States, 29607
Contact: Melissa Beckman       melissa_beckman@bshsi.org   
Principal Investigator: Robert Siegel, MD.         
United States, Tennessee
University of Tennessee Medical Center Recruiting
Knoxville, Tennessee, United States, 37920
Contact: Emily Byers, BSN, RN    865-305-7136    ebyers@utuck.edu   
Principal Investigator: Joseph Kelley, MD         
United States, Virginia
Bon Secours Richmond Recruiting
Richmond, Virginia, United States, 23114
Contact: Melissa Godsey    804-893-8611    melissa_godsey@bshsi.org   
Principal Investigator: William J Irvin, MD         
Sponsors and Collaborators
Altor BioScience
NantCell, Inc.

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Responsible Party: Altor BioScience
ClinicalTrials.gov Identifier: NCT03520686     History of Changes
Other Study ID Numbers: QUILT2.023
First Posted: May 10, 2018    Key Record Dates
Last Update Posted: October 11, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Altor BioScience:
Pembrolizumab
N-803
Non-Small Cell Lung Cancer
Immunotherapy
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents