Marrow Infiltrating Lymphocytes - Non-Small Cell Lung Cancer (MILs™ - NSCLC) Alone or in Combination With Nivolumab With or Without Tadalafil in Locally Advanced and Unresectable or Metastatic NSCLC

NCT04069936 | Terminated Phase 2 FDA Drug

• 1 other identifier: CLN-P18001
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to determine the safety and efficacy of MILs™ - NSCLC alone and in combination with nivolumab with or without tadalafil in subjects with locally advanced and unresectable or metastatic NSCLC who are refractory or relapsing to a PD-1 containing regimen.

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

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Adverse Events per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0

  Incidence, intensity, and type of AE

  From ICF through 100 days after the last dose of study treatment

• Serious Adverse Events per NCI-CTCAE version 5.0

  Incidence, intensity, and type of SAE

  From ICF through 100 days after the last dose of study treatment

• Overall Response Rate (ORR) of MILs™ - NSCLC in combination with nivolumab with or without tadalafil

  Proportion of subjects with reduction in tumor burden of a predefined amount per RECIST 1.1

  24 months

Secondary Outcomes (16)

• Duration of response

  up to 5 years after treatment discontinuation

• Disease control rate

  up to 5 years after treatment discontinuation

• Progression-free survival

  up to 5 years after treatment discontinuation

• Overall survival

  up to 5 years after treatment discontinuation

• Overall Response Rate (ORR) of MILs™ - NSCLC

  24 months

Study Arms (1)

MILs™ - NSCLC plus nivolumab with or without tadalafil

EXPERIMENTAL

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 with or without tadalafil.

Biological: MILs™ - NSCLC; Biological: nivolumab; Drug: tadalafil

Interventions

MILs™ - NSCLC BIOLOGICAL

To evaluate the safety of MILs™ - NSCLC alone in subjects with locally advanced and unresectable or metastatic NSCLC

Also known as: Marrow Infiltrating Lymphocytes

MILs™ - NSCLC plus nivolumab with or without tadalafil

nivolumab BIOLOGICAL

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

MILs™ - NSCLC plus nivolumab with or without tadalafil

tadalafil DRUG

To evaluate the efficacy of MILs™ - NSCLC in combination with nivolumab with or without tadalafil in subjects with locally advanced and unresectable or metastatic NSCLC

MILs™ - NSCLC plus nivolumab with or without tadalafil

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• Locally advanced and unresectable, or metastatic NSCLC.
• Histologically or cytologically confirmed, either squamous or non-squamous NSCLC.
• Measurable disease as per RECIST 1.1
• Willingness to undergo bone marrow aspiration (BMA).
• No more than one treatment regimen following an anti-PD-1 antibody containing treatment regimen prior to BMA collection.
• a. Subjects may have BMA collected while on an anti-PD-1 antibody containing treatment regimen or while on a treatment regimen immediately following an anti-PD-1 antibody containing treatment regimen.
• BMA may be collected while on an anti-PD-1 antibody containing treatment regimen or while on a treatment regimen immediately following an anti-PD-1 antibody containing treatment regimen. However, the subjects must have radiographic evidence of disease progression prior to lymphodepletion.
• ≥ 21 days have lapsed since last cytotoxic chemotherapy treatment prior to collection of the BMA.
• Previous treatment with the appropriate targeted therapy if the subject has known EGFR/ALK/ROS1 rearrangements.
• 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.
• 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) \</= 3.0 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 \>/= 0.7 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.
• 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.
• 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.

You may not qualify if:

• Insufficient activation/expansion of T cells or other problems with the subject's MILs™ - NSCLC product which would prohibit administration.
• Major surgical procedure within 7 days of the first dose of lymphodepletion treatment.
• 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.
• 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. Subjects with asymptomatic untreated CNS disease may undergo BMA prior to treatment of such disease.
• Infection requiring treatment with intravenous antibiotics, antifungal, or antiviral agents within 7 days prior to the BMA.
• Presence of an autoimmune disease requiring active systemic treatment.
• 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.
• Known diagnosis of human immunodeficiency virus (HIV) or active viral hepatitis.
• Administration of neutrophil growth factor support within 14 days prior to the BMA.
• Use of systemic corticosteroids (glucocorticoids) for greater than one day within 28 days prior to the BMA.
• Planned use of systemic corticosteroids (glucocorticoids) for greater than one day within 28 days prior to MILs™ - NSCLC administration.
• 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.
• Subjects with history of life-threatening toxicity related to prior immune therapy except those that are unlikely to re-occur with standard countermeasures.
• Receipt of live attenuated vaccine within 30 days of planned Day 0.
• History of allergy or hypersensitivity to MILs™-NSCLC, cyclophosphamide, fludarabine, nivolumab, tadalafil or their components.

Sponsors & Collaborators

• WindMIL Therapeutics: lead
• Bristol-Myers Squibb: collaborator

Study Sites (10)

City of Hope

Duarte, California, 91010, United States

Location

University of California - Los Angeles

Los Angeles, California, 90095, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Neoplasm Metastasis

Interventions

Nivolumab; Tadalafil

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 with or without tadalafil.

Study Record Dates

• First Submitted: August 16, 2019
• First Posted: August 28, 2019
• Study Start: October 15, 2019
• Primary Completion: October 28, 2021
• Study Completion: November 30, 2021
• Last Updated: August 2, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)