MIDRIX4-LUNG Dendritic Cell Vaccine in Patients With Metastatic Non-small Cell Lung Cancer

NCT04082182 | Unknown Phase 1 DMC

• 1 other identifier: MIDRIX4-LUNG
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

MIDRIX4-LUNG is a novel tetravalent autologous dendritic cell vaccine in metastatic non-small cell lung cancer patients. This first-in-human study aims to primarily establish maximal tolerated dose of MIDRIX4-LUNG administered i.v.

Conditions

Non-small Cell Lung Cancer Metastatic

Keywords

dendritic cell; vaccine; immunotherapy

Outcome Measures

Primary Outcomes (2)

• Toxicity as defined by common toxicity criteria v5.0

  Safety and tolerability of preparing and administrating an autologous dendritic cell-based vaccine in advanced non-small cell lung cancer patients.

  From the day of leukapheresis until 3-4 weeks after the last vaccine dose level, i.e. 3 to 5 months depending on the number of doses that can be administered

• Maximal tolerated dose

  The maximal tolerated dose will be defined from the intra-patient dose excalation scheme

  From the day of leukapheresis until 3-4 weeks after the last vaccine dose level, i.e. 3 to 5 months depending on the number of doses that can be administered

Secondary Outcomes (6)

• Success rate (%) of producing sufficient dendritic cells for vaccination

  From the day of leukapheresis until the last vaccine dose level, i.e. 2 to 4 months depending on the number of doses that can be administered

• Number of vaccine-induced immunological responses as measured by in vitro immunomonitoring assays.

  From the day of leukapheresis until 3-4 weeks after the last vaccine dose level, i.e. 3 to 5 months depending on the number of doses that can be administered. Whenever possible, repeat testing will be performed 3 and 6 months after the last vaccine dose.

• Number of vaccine-induced immunological responses as measured by in vivo immunomonitoring test.

  From the day of leukapheresis until 3-4 weeks after the last vaccine dose level, i.e. 3 to 5 months depending on the number of doses that can be administered. Whenever possible, repeat testing will be performed 3 and 6 months after the last vaccine dose.

• Clinical activity of this type of vaccine as reflected by relapse-free survival

  From the day of leukapheresis onwards during 1 year

• Clinical activity of this type of vaccine as reflected by median progression-free survival

  From the day of leukapheresis onwards during 1 year

Study Arms (1)

DC immunotherapy

EXPERIMENTAL

Intra-patient dose escalation of intravenous MIDRIX4-LUNG autologous DC vaccine

Biological: Dendritic cell immunotherapy; Biological: Antigen-specific DTH; Biological: Control DTH

Interventions

Dendritic cell immunotherapy BIOLOGICAL

Intravenous infusions of MIDRIX4-LUNG DCs every 2 weeks, using an intra-patient dose escalation scheme progressing along the following range: 10 x10E6 DCs (minimal dose), 20 x 10E6 DCs, 40 x 10E6 DCs, 80 x 10E6 DCs, 100 x 10E6 DCs (maximal dose), until exhaustion of the batch or occurrence of grade ≥3 toxicity event

Also known as: DC vaccination

DC immunotherapy

Antigen-specific DTH BIOLOGICAL

Intradermal injection of 1 x 10E6 MIDRIX4-LUNG DCs at baseline and after completion of all i.v. DC vaccination rounds. This is used for assessment of induction of antigen-specific immune responses as part of in vivo immunomonitoring (delayed-type hypersensitivity cutaneous reaction as test read-out)

Also known as: In vivo immunomonitoring - positive test

DC immunotherapy

Control DTH BIOLOGICAL

Intradermal injection of 1 x 10E6 MIDRIX-CTRL DCs at baseline and after completion of all i.v. DC vaccination rounds. This is used for assessment of background (i.e. non-antigen-specific) reactivity (delayed-type hypersensitivity cutaneous reaction as test read-out)

Also known as: In vivo immunomonitoring - negative control

DC immunotherapy

Eligibility Criteria

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

You may qualify if:

• Male and female patients older than 18 years with histologically or cytologically proven diagnosis of non-small cell lung cancer, newly diagnosed or recurrent stage IV, or stage IIIB not amenable to radical chemoradiotherapy (TNM 8th Edition), and for which no standard-of-care therapy is applicable or available at the time of enrollment
• Documented brain metastasis must be either asymptomatic or stabilized after adequate radiotherapeutic treatment as per institutional practice
• WHO-ECOG performance status 0 to 2 and absence of any persisting and assessable toxicity \> CTC grade 2 due to a previous therapy (e.g. brain radiotherapy)
• Before patient registration and screening, written informed consent must be given for the interventional study and for the "Prelevation and storage of human tissues and cells" according to ICH/GCP and institutional practice.
• Adequate organ function, including:
• Adequate bone marrow reserve: absolute neutrophil count \> 1.5\*10E9/L, platelet count \> 100\*10E9/L, and Hb \> 9.0 g/dL
• Sufficient renal function as defined by eGFR \> 40 ml/min
• Sufficient hepatic function as defined by total bilirubin ≤1.5× ULN OR direct bilirubin within normal limits for participants with total bilirubin levels \>1.5× ULN; AST and ALT ≤ 2.5x ULN
• Having passed all tests defined in the institutional Leukapheresis Donor Fitness Screening, including:
• Adequate peripheral vein access to perform leukapheresis
• Adequate coagulation function defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless the participant is receiving anticoagulant therapy
• Negative test results for HBs-antigen, anti-HBc-serology, anti-HCV serology, anti-HIV1-2 serology, anti-CMV IgM, anti-Syphilis (Treponema pallidum) serology
• Negative test results for Epstein-Barr virus (IgG and IgM) and for toxoplasmosis (IgG and IgM)
• For female participants: a negative serum beta-HCG test result less than 1 week before the day of leukapheresis
• For female participants with child-bearing potential, the willingness to follow contraceptive guidance and pregnancy testing during the projected duration of the trial (see Appendix B for Contraceptive Guidance and Pregnancy Testing)

You may not qualify if:

• Presence of oncogenic driver genomic alterations for which a targeted therapy is available
• Concomitant participation in another clinical interventional trial
• Prior treatment with autologous or allogeneic dendritic cell-based vaccines
• NSCLC with large-cell neuro-endocrine or sarcomatoid histology
• Prior malignancy, except for adequately treated basal cell, superficial or in situ cancer of the bladder or the cervix, or other cancer for which the patient has been disease-free for at least five years.
• Dermatological pathology interfering with the in vivo immunomonitoring readout (DTH skin test)
• Untreated brain metastases with neurological symptoms or brain metastasis requiring a daily intake of steroids of \> 10 mg oral prednisolone or equivalent.
• Disease requiring chronic treatment with systemic glucocorticosteroids with a daily dose \> 10 mg oral prednisolone or equivalent, or other immunosuppressive drugs. Inhaled corticosteroids and topical corticosteroids on skin sites other than those used for DTH are allowed.
• Chronic or active concomitant infection requiring active therapy, including including HIV, viral hepatitis (HBV, HCV), CMV or fungal infection
• Autoimmune disease requiring active treatment at the time of the study
• Organ allograft
• Chronic comorbidity (such as asthma, COPD, heart failure, renal failure, arterial hypertension or diabetes mellitus) that is uncontrolled or not stabilized under medication at the time of study enrollment, OR stable yet severe enough to constitute an unwarranted high risk for the investigational cellular therapy.
• For female participants: pregnancy or lactation, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 90 days after the last dose of trial treatment
• Any organic brain syndrome or other significant psychiatric abnormality which would comprise the ability to give informed consent and preclude participation in the full protocol and follow-up.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Sponsors & Collaborators

• University Hospital, Ghent: lead
• University Ghent: collaborator
• Kom Op Tegen Kanker: collaborator

Study Sites (1)

Ghent University Hospital

Ghent, B-9000, Belgium

Location

Related Publications (1)

• Brabants E, Heyns K, De Smet S, Devreker P, Ingels J, De Cabooter N, Debacker V, Dullaers M, VAN Meerbeeck JP, Vandekerckhove B, Vermaelen KY. An accelerated, clinical-grade protocol to generate high yields of type 1-polarizing messenger RNA-loaded dendritic cells for cancer vaccination. Cytotherapy. 2018 Sep;20(9):1164-1181. doi: 10.1016/j.jcyt.2018.06.006. Epub 2018 Aug 16.

  PMID: 30122654 BACKGROUND

Study Officials

• Karim Y Vermaelen, MD, PhD

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof Dr Karim Vermaelen

Model Details: intra-patient dose escalation scheme

Study Record Dates

• First Submitted: June 20, 2019
• First Posted: September 9, 2019
• Study Start: August 26, 2019
• Primary Completion: June 7, 2021
• Study Completion: December 31, 2021
• Last Updated: March 30, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)