Clinical Trials /

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

NCT04069936

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CLN-P18001
  • NCT ID: NCT04069936

Conditions

  • 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

Interventions

DrugSynonymsArms
MILs™ - NSCLCMarrow Infiltrating LymphocytesMILs™ - NSCLC plus nivolumab
nivolumabMILs™ - NSCLC plus nivolumab

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
MILs™ - NSCLC plus nivolumabExperimentalLocally 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.
  • MILs™ - NSCLC
  • nivolumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Incidence, intensity, and type of AE

Secondary Outcome Measures

Measure:Duration of response
Time Frame:up to 5 years after treatment discontinuation
Safety Issue:
Description: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
Measure:Disease control rate
Time Frame:up to 5 years after treatment discontinuation
Safety Issue:
Description:Proportion of subjects in the efficacy population who achieve an Investigator-assessed confirmed CR, PR, or SD per RECIST 1.1
Measure:Progression-free survival
Time Frame:up to 5 years after treatment discontinuation
Safety Issue:
Description:Date of first the administration of MILs™ - NSCLC until documented PD or death due to any cause, whichever occurs first
Measure:Overall survival
Time Frame:up to 5 years after treatment discontinuation
Safety Issue:
Description:Duration from the date of administration of MILs™ - NSCLC until death due to any cause
Measure:Overall Response Rate (ORR) of MILs™ - NSCLC
Time Frame:24 months
Safety Issue:
Description:Proportion of subjects with reduction in tumor burden of a predefined amount per RECIST 1.1
Measure: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
Safety Issue:
Description:Pulse rate in beats/minute
Measure: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
Safety Issue:
Description:Weight in pounds
Measure: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
Safety Issue:
Description:Systolic and diastolic blood pressure in mmHg
Measure: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
Safety Issue:
Description:Respiratory rate in breaths/minute
Measure: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
Safety Issue:
Description:Termperature in Fahrenheit
Measure: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
Safety Issue:
Description:Clinical chemistry results will be summarized and changes from baseline provided
Measure: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
Safety Issue:
Description:Hematology results will be summarized and changes from baseline provided
Measure: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
Safety Issue:
Description:Coagulation results will be summarized in data listings
Measure: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
Safety Issue:
Description:Urinalysis results will be summarized in data listings
Measure: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
Safety Issue:
Description:ECGs results will be summarized and changes from baseline provided
Measure: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
Safety Issue:
Description:Physical examinations will be performed by the Investigators and any new clinically significant or changes in medical conditions will be reported as adverse events

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:WindMIL Therapeutics

Trial Keywords

  • metastatic
  • locally advanced
  • lung cancer
  • non-small cell lung cancer
  • unresectable
  • NSCLC
  • cell therapy
  • autologous cell therapy
  • adoptive cell therapy

Last Updated

November 13, 2020