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Marrow Infiltrating Lymphocytes - Non-Small Cell Lung Cancer (MILs™ - NSCLC) Alone or in Combination With Nivolumab in Locally Advanced and Unresectable or Metastatic NSCLC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04069936
Recruitment Status : Recruiting
First Posted : August 28, 2019
Last Update Posted : April 29, 2020
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
WindMIL Therapeutics

Brief Summary:
The purpose of this study is to determine the safety and efficacy of MILs™ - NSCLC alone and in combination with nivolumab in subjects with locally advanced and unresectable or metastatic NSCLC who are refractory or relapsing to a PD-1 containing regimen.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Lung Cancer Lung Cancer Metastatic Lung Cancer, Non-small Cell Non Small Cell Lung Cancer Metastatic NSCLC Non-small Cell Lung Cancer Non-small Cell Lung Cancer Metastatic Biological: MILs™ - NSCLC Biological: nivolumab Phase 2

Detailed Description:
This study will examine the safety and efficacy of Marrow Infiltrating Lymphocytes-Non-Small Cell Lung Cancer (MILs™ - NSCLC) combined with nivolumab in subjects with locally advanced and unresectable and metastatic NSCLC who were refractory to, or have relapsed on, an anti-PD-1 containing regimen. MILs™ - NSCLC are an adoptive cell therapy product derived via the activation and expansion of bone marrow T cells. Subjects will have bone marrow harvested during the Screening Period which will be used to manufacture the MILs™ - NSCLC. The MILs™ - NSCLC will then be administered on Day 0. Nivolumab will be administered on Day 1 and will continue every four weeks until treatment discontinuation.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 23 participants
Intervention Model: Sequential Assignment
Intervention Model Description: In Part 1, approximately 3-6 subjects will be treated with MILs™ - NSCLC alone. Following Part 1, approximately 20 subjects will be treated with MILs™ - NSCLC plus nivolumab.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2a, Open-Label, Multi-Center Study to Assess the Efficacy and Safety of Marrow Infiltrating Lymphocytes - Non-Small Cell Lung Cancer (MILs™ - NSCLC) Alone or in Combination With Nivolumab in Subjects With Locally Advanced and Unresectable or Metastatic NSCLC Previously Treated With Anti-PD-1
Actual Study Start Date : October 15, 2019
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : June 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: MILs™ - NSCLC plus nivolumab
Locally advanced and unresectable and metastatic NSCLC subjects previously treated with anti-programmed cell death-1 (PD-1) will be treated with MILs™ - NSCLC plus nivolumab.
Biological: MILs™ - NSCLC
To evaluate the safety of MILs™ - NSCLC alone in subjects with locally advanced and unresectable or metastatic NSCLC
Other Name: Marrow Infiltrating Lymphocytes

Biological: nivolumab
To evaluate the efficacy of MILs™ - NSCLC in combination with nivolumab in subjects with locally advanced and unresectable or metastatic NSCLC




Primary Outcome Measures :
  1. Adverse Events per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 [ Time Frame: From ICF through 100 days after the last dose of study treatment ]
    Incidence, intensity, and type of AE

  2. Serious Adverse Events per NCI-CTCAE version 5.0 [ Time Frame: From ICF through 100 days after the last dose of study treatment ]
    Incidence, intensity, and type of SAE

  3. Overall Response Rate (ORR) of MILs™ - NSCLC in combination with nivolumab [ Time Frame: 24 months ]
    Proportion of subjects with reduction in tumor burden of a predefined amount per RECIST 1.1


Secondary Outcome Measures :
  1. Duration of response [ Time Frame: up to 5 years after treatment discontinuation ]
    Duration from first documented evidence of CR or PR until the first documented evidence of PD or death due to any cause, whichever occurs first

  2. Disease control rate [ Time Frame: up to 5 years after treatment discontinuation ]
    Proportion of subjects in the efficacy population who achieve an Investigator-assessed confirmed CR, PR, or SD per RECIST 1.1

  3. Progression-free survival [ Time Frame: up to 5 years after treatment discontinuation ]
    Date of first the administration of MILs™ - NSCLC until documented PD or death due to any cause, whichever occurs first

  4. Overall survival [ Time Frame: up to 5 years after treatment discontinuation ]
    Duration from the date of administration of MILs™ - NSCLC until death due to any cause

  5. Overall Response Rate (ORR) of MILs™ - NSCLC [ Time Frame: 24 months ]
    Proportion of subjects with reduction in tumor burden of a predefined amount per RECIST 1.1

  6. Safety of MILs™ - NSCLC alone and in combination with nivolumab as assessed by vital signs (pulse rate) [ Time Frame: From ICF through 100 days after the last dose of study treatment ]
    Pulse rate in beats/minute

  7. Safety of MILs™ - NSCLC alone and in combination with nivolumab as assessed by vital signs (weight) [ Time Frame: From ICF through 100 days after the last dose of study treatment ]
    Weight in pounds

  8. Safety of MILs™ - NSCLC alone and in combination with nivolumab as assessed by vital signs (blood pressure) [ Time Frame: From ICF through 100 days after the last dose of study treatment ]
    Systolic and diastolic blood pressure in mmHg

  9. Safety of MILs™ - NSCLC alone and in combination with nivolumab as assessed by vital signs (respiratory rate) [ Time Frame: From ICF through 100 days after the last dose of study treatment ]
    Respiratory rate in breaths/minute

  10. Safety of MILs™ - NSCLC alone and in combination with nivolumab as assessed by vital signs (temperature) [ Time Frame: From ICF through 100 days after the last dose of study treatment ]
    Termperature in Fahrenheit

  11. Safety of MILs™ - NSCLC alone and in combination with nivolumab by liver function (e.g. ALT (U/L), AST (U/L), albumin (g/dL), total bilirubin (mg/dL)), kidney function (e.g. creatinine (mg/dL) and endocrine function (e.g. T3 free (ng/dL),T4 free (ng/dL)) [ Time Frame: From ICF through 100 days after the last dose of study treatment ]
    Clinical chemistry results will be summarized and changes from baseline provided

  12. Safety of MILs™ - NSCLC alone and in combination with nivolumab by cell count (e.g. RBC (10^6/uL), WBC (10^3/uL), absolute cell count (10^3/uL), Hct (%) and Hgb (g/dL) [ Time Frame: From ICF through 100 days after the last dose of study treatment ]
    Hematology results will be summarized and changes from baseline provided

  13. Safety of MILs™ - NSCLC alone and in combination with nivolumab as assessed by APTT (seconds), fibrinogen (mg/dL), INR and protime (seconds) [ Time Frame: From ICF through 100 days after the last dose of study treatment ]
    Coagulation results will be summarized in data listings

  14. Safety of MILs™ - NSCLC alone and in combination with nivolumab as assessed by urine appearance, color, pH, specific gravity and presence of blood, bilirubin, glucose, ketone, leukocyte esterase, nitrite, protein, urobilinogen [ Time Frame: From ICF through 100 days after the last dose of study treatment ]
    Urinalysis results will be summarized in data listings

  15. Safety of MILs™ - NSCLC alone and in combination with nivolumab by electrocardiograms (ECGs) assessed by Investigators as normal, abnormal clinically significant or abnormal not clinically significant [ Time Frame: From ICF through 100 days after the last dose of study treatment ]
    ECGs results will be summarized and changes from baseline provided

  16. Safety of MILs™ - NSCLC alone and in combination with nivolumab by physical examination with abnormalities reported as adverse events [ Time Frame: From ICF through 100 days after the last dose of study treatment ]
    Physical examinations will be performed by the Investigators and any new clinically significant or changes in medical conditions will be reported as adverse events



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
  2. Locally advanced and unresectable, or metastatic NSCLC.
  3. Histologically or cytologically confirmed, either squamous or non-squamous NSCLC.
  4. Measurable disease as per RECIST 1.1 with radiographic evidence of disease progression.
  5. Willingness to undergo bone marrow aspiration (BMA).
  6. No more than one treatment regimen following an anti-PD-1 antibody containing treatment regimen prior to BMA collection
  7. ≥ 21 days have lapsed since last cytotoxic chemotherapy treatment prior to collection of the BMA.
  8. Previous treatment with the appropriate targeted therapy if the subject has known EGFR/ALK/ROS1 rearrangements.
  9. Willingness to provide a fresh tumor biopsy during Screening Period or formalin-fixed, paraffin-embedded tissue collected at the time of most recent relapse. Note: Archival tissue regardless of biopsy date may be considered.
  10. Adequate renal, hepatic and bone marrow function defined as total bilirubin </= 1.5 x ULN (except for subjects with Gilbert's disease ≤ 3.0 x ULN with direct bilirubin </= 1.5 x ULN ). Aminotransferase (AST) / Alanine Aminotransferase (ALT) </= 2.5 X ULN (subjects with liver involvement will be allowed </= 5.0 X ULN). Serum creatinine </= 1.5 x ULN; if serum creatinine is 1.5 to 2.0 × ULN, then the creatinine clearance (calculated using the Cockcroft-Gault formula or measured) must be ≥ 40 mL/min. Lymphocyte >/= 1.0 x 10^9/L. ANC >/= 1.5 x 10^9/L. Platelets >/= 100 × 10^9/L. WBC >/= 2.0 ×10^9/L. Hemoglobin > 9.0 g/dL.
  11. Women of childbearing potential and male subjects (even if they are surgically sterilized or had a vasectomy) and their partners must agree to abstain or to use an effective form of birth control during the study for at least 6 months following administration of the last dose of lymphodepletion or for at least 5 months following the last dose of nivolumab for females and 7 months for males, whichever is longer. In addition, male subjects must not donate sperm during this period.
  12. Capable of giving and has provided a signed ICF, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion Criteria:

  1. Insufficient activation/expansion of T cells or other problems with the subject's MILs™ - NSCLC product which would prohibit administration.
  2. Major surgical procedure within 7 days of the first dose of lymphodepletion treatment.
  3. Prior malignancy active within the previous 3 years from date of BMA collection except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
  4. Subjects with symptomatic uncontrolled brain metastases requiring treatment with steroids or anti-seizure medications within 28 days prior to the BMA are excluded. However, participants with brain metastases that have been previously treated and are stable on subsequent scan(s) are allowed and subjects with untreated possible brain metastases that are new at the time of screening and are < 1 cm and asymptomatic are allowed.
  5. Infection requiring treatment with intravenous antibiotics, antifungal, or antiviral agents within 7 days prior to the BMA.
  6. Presence of an autoimmune disease requiring active systemic treatment.
  7. Clinically significant, uncontrolled cardiovascular disease, including congestive heart failure Grade III or IV according to the New York Heart Association classification, myocardial infarction or unstable angina within the previous 6 months prior to BMA collection.
  8. Known diagnosis of human immunodeficiency virus (HIV) or active viral hepatitis.
  9. Administration of neutrophil growth factor support within 14 days prior to the BMA.
  10. Use of systemic corticosteroids (glucocorticoids) for greater than one day within 28 days prior to the BMA.
  11. Planned use of systemic corticosteroids (glucocorticoids) for greater than one day within 28 days prior to MILs™ - NSCLC administration.
  12. Prior radiation to both sides of the pelvis. Prior radiation to one side of the pelvis is permitted as long as the other side of the pelvis.
  13. Subjects with history of life-threatening toxicity related to prior immune therapy except those that are unlikely to re-occur with standard countermeasures.
  14. Receipt of live attenuated vaccine within 30 days of planned Day 0.
  15. History of allergy or hypersensitivity to MILs™-NSCLC, cyclophosphamide, fludarabine, nivolumab or their components.
  16. Pregnant or lactating females.
  17. Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's opinion, could affect the safety of the subject or impair the assessment of study results.
  18. Unwilling or unable to comply with the protocol.

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): NCT04069936


Contacts
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Contact: Amanda L Seiz 6186702604 seiz@windmiltx.com
Contact: Monil Shah, PharmD 2019788032 shah@windmiltx.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Tiffini Gosha    626-218-9163    tgosha@coh.org   
University of California - Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Joy Torrez    310-794-5418    JValadez@mednet.ucla.edu   
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Wesley Curry    813-745-3861    wesley.curry@moffitt.org   
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Tolu Adewuya    404-778-5157    tolu.adewuya@emory.edu   
United States, Michigan
Karmanos Cancer Center Recruiting
Detroit, Michigan, United States, 48201
Contact: Kasie Lashley    313-576-9243    lashleyk@karmanos.org   
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Martin Edelman, MD    888-369-2427      
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Davinia McComb    615-329-7478    Davinia.McComb@sarahcannon.com   
Sponsors and Collaborators
WindMIL Therapeutics
Bristol-Myers Squibb
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Responsible Party: WindMIL Therapeutics
ClinicalTrials.gov Identifier: NCT04069936    
Other Study ID Numbers: CLN-P18001
First Posted: August 28, 2019    Key Record Dates
Last Update Posted: April 29, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 WindMIL Therapeutics:
metastatic
locally advanced
lung cancer
non-small cell lung cancer
unresectable
NSCLC
cell therapy
autologous cell therapy
adoptive cell therapy
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents