Personalized DC Vaccines in Non Small Cell Lung Cancer

NCT05195619 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: CHUV-DO-0022-LUNGVAC-2019
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Phase Ib clinical trial using autologous dendritric cell (DC) vaccine loaded with personalized peptides (PEP) given in combination with low-dose cyclophosphamide, as standard of care (SOC) therapy in patients with advanced or recurrent metastatic NSCLC.

Conditions

Non-small Cell Lung Cancer

Keywords

non-small cell lung cancer; vaccine; cyclophosphamide

Outcome Measures

Primary Outcomes (3)

• Number of patients who receive at least one dose of vaccine

  Feasibility will be evaluated by the number of patients who receive at least one dose of vaccine, among all enrolled patients.

  3.5 years after study activation

• Assessment of adverse events

  Safety will be assessed by recording all adverse events (AEs) observed from informed consent form (ICF) signature until 30 days after last injection of DC vaccine/cyclophosphamide.

  from informed consent form (ICF) signature until 30 days after last injection of DC vaccine/cyclophosphamide

• Assessment of treatment-limiting toxicities

  Collection of events defined as related to vaccine administration. Patients showing any of them will be withdrawn from the study.

  21 days (i.e. during the full vaccination period)

Secondary Outcomes (5)

• Overall response rate 1 (ORR1)

  From enrollment until 6 months

• Overall response rate 2 (ORR2)

  From enrollment to progression of the disease (ORR2)

• Duration of response (DoR)

  up to 2 years from 1st vaccine injection

• Progression-free survival (PFS)

  up to 2 years from 1st vaccine injection

• Overall survival (OS)

  up to 2 years from 1st vaccine injection

Study Arms (2)

Cohort 1

EXPERIMENTAL

metastatic NSCLC of any histology without any actionable oncogenic driver treated by SOC. Maintenance treatment with pemetrexed and/or maintenance/continuation of pembrolizumab, nivolumab or atezolizumab is allowed.

Biological: Autologous dendritic cell vaccine loaded with personalized peptides (PEP-DC vaccine); Drug: Low dose cyclophosphamide

Cohort 2

EXPERIMENTAL

metastatic NSCLC with actionable oncogenic driver such as EGFR mutation, ROS-1 or ALK rearrangement, currently receiving osimertinib, alectinib, lorlatinib, brigatinib or crizotinib as per SOC in each disease entity.

Biological: Autologous dendritic cell vaccine loaded with personalized peptides (PEP-DC vaccine); Drug: Low dose cyclophosphamide

Interventions

Autologous dendritic cell vaccine loaded with personalized peptides (PEP-DC vaccine) BIOLOGICAL

Patients will receive six DC vaccinations Q3W (±3 days) in combination with low dose cyclophosphamide the day before vaccination. Each dose of vaccine (PEP-DC) will be split into two injections, which will be administered on W2D2 of each cycle, subcutaneously. Patients will be vaccinated until vaccine exhaustion, disease progression, major toxicity or patient withdrawal, whichever is earlier. Additional DC vaccines may be administered Q3W (±3 days) if available until vaccine exhaustion or disease progression, whichever is earlier.

Cohort 1; Cohort 2

Low dose cyclophosphamide DRUG

Patients will receive six DC vaccinations Q3W (±3 days) in combination with low dose cyclophosphamide the day before vaccination.

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form
• Histologically confirmed diagnosis of the NSCLC
• Patients with metastatic, recurrent and/or unresectable NSCLC from stage IIIA (not amenable to radical treatment) to stage IVB provided they have not experienced disease progression on their current standard-of-care therapy at screening, as compared to the tumor assessment at the initiation of standard-of-care therapy as confirmed by Computed tomography/Magnetic Resonance Imaging (CT/MRI).
• Patients may have received any number of prior treatments without restriction and any prior immunotherapy before enrollment to the study. However, only patients receiving the maintenance/continuation of standard of care (SOC) treatment options mentioned below are permitted to enter the study.
• Patient may receive only the following maintenance/continuation of SOC therapy during study treatment, as indicated in each case.
• Cohort 1: advanced or metastatic non-small cell lung cancer of any histology without any actionable oncogenic driver treated by SOC. Maintenance pemetrexed and/or maintenance pemetrexed + pembrolizumab, pembrolizumab alone, nivolumab, or atezolizumab is allowed.
• Cohort 2: advanced or metastatic NSCLC with actionable oncogenic driver such as Epidermal Growth Factor Receptor (EGFR) or anaplastic lymphoma kinase (ALK) or ROS-1-rearrangement, currently receiving osimertinib, alectinib, lorlatinib, brigatinib or crizotinib as per SOC in each disease entity
• Top 10 personalized peptides (PEP) for the preparation of PEP-DC vaccine has been determined before screening.
• Patients \>18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 21 days prior registration:
• Hemoglobin ≥ 90 g/L
• Neutrophil count ≥ 1.0 G/L (independently of administration of growth factor within 4 weeks prior registration)
• Platelet count ≥ 100 G/L
• Serum creatinine ≤ 1.5x Institutional Upper Limit of Normal (ULN), or Creatinine clearance (CrCl) ≥ 40 mL/min (calculated using the Cockcroft-Gault formula.

You may not qualify if:

• Pregnant or breast-feeding women
• Other malignancy within 2 years prior study enrollment, except for those treated with surgical intervention as curative intent in remission.
• Current, recent (within 4 weeks prior registration), or planned participation in an experimental drug study
• Patients who show signs of progression according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 at screening
• Planned SOC therapy other than the following:
• Cohort 1: Maintenance pemetrexed and/or maintenance pemetrexed + pembrolizumab, pembrolizumab alone, nivolumab or atezolizumab is allowed.
• Cohort 2: osimertinib, alectinib, lorlatinib, brigatinib or crizotinib
• Known hypersensitivity to any component of the study treatment
• Any contraindication for using cyclophosphamide
• Treatment with systemic immunosuppressive medications within 4 weeks prior vaccination (more than an equivalent of 10mg prednisone per day). Patient who has to receive steroid treatment as premedication before pemetrexed are eligible.
• Administration of a live, attenuated vaccine within 8 weeks before registration
• Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine within 4 weeks prior registration or at any time during the study.
• Positive serology defined by the following laboratory results:
• Positive test for Human Immunodeficiency Virus (HIV)
• Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening).

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Study Sites (1)

CHUV Oncology Department

Lausanne, Canton of Vaud, 1011, Switzerland

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cyclophosphamide

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A total of 16 evaluable patients will be recruited, eight in each cohort. Cohort 1: metastatic non-small cell lung cancer of any histology without any actionable oncogenic driver treated by SOC. Maintenance treatment with pemetrexed and/or maintenance/continuation of pembrolizumab, nivolumab or atezolizumab is allowed. Cohort 2: metastatic NSCLC with actionable oncogenic driver such as EGFR mutation, ROS-1 or ALK rearrangement, currently receiving osimertinib, alectinib, lorlatinib, brigatinib or crizotinib as per SOC in each disease entity.

Study Record Dates

• First Submitted: December 17, 2021
• First Posted: January 19, 2022
• Study Start: March 22, 2022
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 10, 2025

Record last verified: 2025-07

Locations

CH (1)