Immunopheresis Alone or in Combination With Paclitaxel or Atezolizumab in Non-small Cell Lung Cancer (NSCLC).

NCT04690686 | Unknown Phase 2 DMC

• 1 other identifier: CP7-008
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

This pilot study aims to evaluate the short-term and long-term safety, tolerability, and effectiveness of immunopheresis with the LW-02 column in removal of sTNFRs from plasma of patients with advanced, refractory NSCLC and to detect a potential disease control signal when employed in combination with low dose chemotherapy (ie, paclitaxel), immunotherapy (ie, atezolizumab) in patients who already failed first-line therapy, or as monotherapy in patients who already have failed second-line therapy.

Conditions

Non Small Cell Lung Cancer

Keywords

NSCLC; Advanced NSCLC

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events

  Treatment-Emergent Adverse Events which will be analysed in study ill be: 1. Adverse Event (AE) 2. Serious Adverse Events (SAE) 3. Adverse Device Effect (ADE) 4. Serious Adverse Device Effect (SADE) Each of the Treatment-Emergent Adverse Events will be assessed for their seriousness, severity \[using NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 v. 5.0\] and causality (relationship with the use of the investigated medical device).

  16 weeks

• Column performance effectiveness

  Column efficiency and effectiveness in removal of sTNF-Rs from patient plasma without clinically-meaningful leaching of capture ligand (SC-TNF-α) - change in sTNF-R and TNF-α plasma levels from initiation to the end of each LW-02 column perfornance effectiveness will be assessed to measure over 30 minutes (sTNF-Rs) and over the duration (leaching) of each procedure, respectively: * Removal of soluble TNF receptor 1 (sTNF-R1) * Removal of soluble TNF receptor 2 (sTNF-R2) * Leaching of sc-TNF-α from the column

  16 weeks

• Incidence of Treatment-Emergent Adverse Events of special interest.

  Incidence of Treatment-Emergent Adverse Events of special interest assessment will include: 1. tumor lysis syndrome and 2. systemic inflammatory response syndrome. These events may or may not be serious and they may or may not be considered related to study treatment. Regardless of relationship or severity, these events will be recorded if they start after the first application of study treatment and will be followed until resolution.

  16 weeks

Secondary Outcomes (10)

• Patient functioninig with Eastern Cooperative Oncology Group (ECOG)

  16 weeks

• Quality of life assessment with EQ-5D-5L scale

  16 weeks

• Quality of life assessment with EORTC-QLQ-C30 scale

  16 weeks

• Quality of life assessment with EORTC-QLQ-LC29 scale

  16 weeks

• Clinical endpoint - overall survival

  16 weeks

Study Arms (3)

LW-02 device immunopheresis combined with atezolizumab

EXPERIMENTAL

LW-02 column immunopheresis treatments \~3x/week for 16 weeks plus atezolizumab 1200 milligrams (mg) q3w until disease progression or loss of clinical benefit, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first \[N=8\]

Device: LW-02 device immunopheresis combined with atezolizumab

LW-02 device immunopheresis combined with weekly paclitaxel

EXPERIMENTAL

LW-02 column immunopheresis treatments \~3x/week for 16 weeks plus paclitaxel 80 mg/m2 /week × 6 followed by 2 weeks rest until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first. \[N=8\]

Device: LW-02 device immunopheresis combined with weekly paclitaxel

LW-02 device immunopheresis

EXPERIMENTAL

LW-02 column immunopheresis treatments \~3x/week for 16 weeks alone until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first. \[N=8\]

Device: LW-02 device immunopheresis

Interventions

LW-02 device immunopheresis combined with atezolizumab DEVICE

The LW-02 device comprises an immunoadsorption affinity column, employing a proprietary human recombinant protein, single chain TNF-α ligand, covalently linked to a bead resin, that both enhances the capture efficiency of sTNF-Rs while avoiding complications from column leaching. Reduced sTNF-R plasma levels may lead to objective tumor responses. In combined treatment arm the immunopheresis procedure is combined with standard dose immunotherapy (atezolizumab) to potentially enhancing its cytotoxic effect.

Also known as: Plasma soluble TNF receptor pulldown + immunotherapy.

LW-02 device immunopheresis combined with atezolizumab

LW-02 device immunopheresis combined with weekly paclitaxel DEVICE

The LW-02 device comprises an immunoadsorption affinity column, employing a proprietary human recombinant protein, single chain TNF-α ligand, covalently linked to a bead resin, that both enhances the capture efficiency of sTNF-Rs while avoiding complications from column leaching. Reduced sTNF-R plasma levels may lead to objective tumor responses. In combined treatment arm the immunopheresis procedure is combined with low dose chemotherapy to potentially enhancing its cytotoxic effect.

Also known as: Plasma soluble TNF receptor pulldown + chemotherapy

LW-02 device immunopheresis combined with weekly paclitaxel

LW-02 device immunopheresis DEVICE

The LW-02 device comprises an immunoadsorption affinity column, employing a proprietary human recombinant protein, single chain TNF-α ligand, covalently linked to a bead resin, that both enhances the capture efficiency of sTNF-Rs while avoiding complications from column leaching. Reduced sTNF-R plasma levels may lead to objective tumor responses.

Also known as: Plasma soluble TNF receptor pulldown

LW-02 device immunopheresis

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form
• Age 18 - 75 years of age
• Able to comply with the study protocol in the investigator's judgment
• Histologically or cytologically documented stage IIIb or stage IV squamous or adenocarcinoma NSCLC that has progressed despite 1 line of chemotherapy that included a platinum salt (Arms 1 and 2) or 2 lines of standard chemotherapy assuming the 1st line included a platinum salt (Arm 3). \[Patients with adenocarcinoma must have confirmed negative status of EGFR gene mutation and ALK fusion gene and ROS1.\]
• Patients who discontinued previous treatments (first- or second-line) due to intolerance are also eligible.
• Staging must be according to the UICC/AJCC system, 7th edition (Detterbeck et al. 2009)
• Pathological characterization may be conducted on tumor specimens from earlier stage disease, but the tumor samples must have been sufficient to confirm squamous or adenocarcinoma histologically
• Combined radiation/chemotherapy treatment (chemoradiation) counts as one prior chemotherapy regimen if \< 6 months have elapsed between the last dose and the date of recurrence
• Adjuvant/neoadjuvant chemotherapy is not counted as a line of treatment except for cases where the relapse is diagnosed \< 6 months from the end of adjuvant/neoadjuvant chemotherapy that included a platinum salt.
• Debulking surgery and anticancer agents used for pleurodesis are not counted as lines of therapy 5. Must be able to provide archival pathological material from primary or metastatic site (formalin-fixed paraffin embedded \[FPPE\] tissue block) for central NSCLC confirmation and verification of NSCLC subtype and tmTNF expression 6. Body mass ≥ 35 kg 7. Life expectancy of at least 3 months with malignancy; expected to live for one year without malignancy. 8. Adequate organ function:
• Hemoglobin ≥ 9.5g/dL (may be achieved with transfusion support)
• Absolute Neutrophil Count (ANC) ≥1.5 × 109/L (without granulocyte colony-stimulating factor support within 2 weeks prior to the first study treatment)
• Platelets (PTL) ≥ 100 × 109/L
• AST/ALT ≤2.5×ULN (patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN; patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 × ULN)
• Serum creatinine (S-Cr) ≤ 1.2 ULN

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Symptomatic CNS metastases
• Leptomeningeal disease
• Uncontrolled pericardial effusion or ascites requiring recurrent drainage procedures
• Previous use of paclitaxel (not applicable for patients enrolled in Arm 3).
• Pregnant or lactating or intending to become pregnant during the study or for at least 5 months after the least study treatment. Women who are not postmenopausal (postmenopausal defined as ≥ 12 months of non-drug-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 2 weeks prior to initiation of study treatment
• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)
• Significant cardiovascular disease, such as New York Heart Association cardiac disease ≥ Class III, myocardial infarction within 3 months, unstable arrhythmias, or unstable angina
• Patients with known coronary artery disease or left ventricular ejection fraction \< 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
• Patient with known persistent, uncontrolled hypotension
• Significant renal disorder requiring dialysis or indication for renal transplant
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to study treatment initiation
• Major surgical procedure within 4 weeks prior to study treatment initiation or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
• Fever, or any active immunosuppressive systemic infection including history of human immunodeficiency virus (HIV) infection
• Other serious diseases (e.g., life expectancy less than 3 months) including active second malignancy except for basal cell carcinoma or cervical carcinoma in situ

Sponsors & Collaborators

• Immunicom Inc: lead

Study Sites (3)

Acibadem Atakent Hospital, Medical Oncology Department

Istanbul, Kucukcekmece, 34303, Turkey (Türkiye)

RECRUITING

Acibadem Maslak Hospital, Medical Oncology Department - coordinating site

Istanbul, Sariyer, 34457, Turkey (Türkiye)

RECRUITING

Acibadem Altunizade Hospital, Mecical Oncology Department

Istanbul, Uskudar, 34662, Turkey (Türkiye)

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Immunotherapy; Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Study Officials

• Adam Ostrowski, MD

  Immunicom Inc

  STUDY DIRECTOR

Central Study Contacts

Adam Ostrowski, MD Medical Director, International - Immunicom, Inc.

CONTACT

+48 606446610; adam.ostrowski@immunicom.com

Robert Segal, MD FACP Chief Medical Officer - Immunicom, Inc.

CONTACT

+1 2672377576; robert.segal@immunicom.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, phase 2a pilot study of Immunicom's LW-02 column-combined with low-dose chemotherapy or immunotherapy.

Study Record Dates

• First Submitted: October 23, 2020
• First Posted: December 31, 2020
• Study Start: October 1, 2020
• Primary Completion: August 31, 2022
• Study Completion: December 31, 2022
• Last Updated: March 8, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

TU (3)