LUNGVAC: Efficacy and Safety of Anti-PD-1/PD-L1 Treatment +/- UV1 Vaccination in Patients With Non-small Cell Lung Cancer

Sponsor
Vestre Viken Hospital Trust (Other)
Overall Status
Recruiting
CT.gov ID
NCT05344209
Collaborator
University Hospital, Akershus (Other), Oslo University Hospital (Other), Haukeland University Hospital (Other), Helse Stavanger HF (Other), Helse Fonna (Other), Helse Nord-Trøndelag HF (Other), St. Olavs Hospital (Other), Alesund Hospital (Other), Helse Forde (Other), University Hospital of North Norway (Other)
138
1
2
58.6
2.4

Study Details

Study Description

Brief Summary

A Randomized, Multicenter Study Investigating Efficacy and Safety of anti-PD-1/PD-L1-treatment +/- UV1 vaccination as first line treatment in patients with inoperable advanced or metastatic non-small cell lung cancer. The objective of the phase 2 study is to induce a meaningful Progression-Free Survival (PFS) benefit in patients with stage IIIB/IIIC or stage IV NSCLC by treating with anti-PD-1/PD-L1 treatment and UV1 vaccination versus anti-PD-1/PD-L1 treatment alone.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

The objective of the phase 2 study is to induce a meaningful Progression-Free Survival (PFS) benefit in patients with stage IIIB/IIIC or stage IV NSCLC by treating with anti-PD-1/PD-L1 treatment and UV1 vaccination versus anti-PD-1/PD-L1 treatment alone.

Patients are randomized to receive anti-PD-1/PD-L1 treatment until progression or unacceptable toxicity, for a maximum of 2 years, with or without 8 injections of 300 μg UV1 and 75 μg GM-CSF (UV1 vaccination). Patients randomized to UV1 vaccination, will start UV1 vaccination the same day as anti-PD-1/PD-L1 treatment is initiated, followed by three vaccinations over the next ten days. Thereafter, one vaccination per anti-PD-1/PD-L1 treatment cycle (c2-5), totaling to 8 UV1 vaccinations

Study Design

Study Type:
Interventional
Anticipated Enrollment :
138 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomized Phase II, Open-label, Multicenter StudyRandomized Phase II, Open-label, Multicenter Study
Masking:
None (Open Label)
Masking Description:
open label
Primary Purpose:
Treatment
Official Title:
A Randomized Phase II, Open-label, Multicenter Study Investigating Efficacy and Safety of Pembrolizumab +/- UV1 Vaccination as First Line Treatment in Patients With Inoperable Advanced or Metastatic Non-small Cell Lung Cancer
Actual Study Start Date :
Aug 12, 2022
Anticipated Primary Completion Date :
Jul 1, 2025
Anticipated Study Completion Date :
Jul 1, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: anti-PD-1/PD-L1 treatment + UV1 vaccination

anti-PD-1/PD-L1 treatment + UV1 vaccination (and sagramostim)

Biological: UV1
UV1 vaccine

Drug: Sagramostim
for stimulation of local dendritic cell population to take up the vaccine and to mature into professional APCs
Other Names:
  • leukine
  • Drug: Anti-PD-1/PD-L1 treatment
    either pembrolizumab, atezolizumab or cemiplimab

    Other: anti-PD-1/PD-L1 treatment

    anti-PD-1/PD-L1 treatment

    Drug: Anti-PD-1/PD-L1 treatment
    either pembrolizumab, atezolizumab or cemiplimab

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) as determined by Blinded Independent Central Review (BICR) [Up to 2 years]

      Evaluate and compare the efficacy of anti-PD-1/PD-L1-treatment with or without UV1 vaccination in patients with stage IIIB/IIIC or stage IV NSCLC.

    Secondary Outcome Measures

    1. Response evaluation [Throughout trial (up to 2 years)]

      Comparison of response rate according to RECIST v1.1 in patients who receive anti-PD-1/PD-L1 treatment and patients who receive anti-PD-1/PD-L1 treatment in combination with UV1.

    2. monitoring AE [continously and until 4 months after discontinuation of study treatment]

      evaluate safety and tolerability in patients who receive anti-PD-1/PD-L1 treatment and patients who receive anti-PD-1/PD-L1 treatment in combination with UV1.

    Other Outcome Measures

    1. molecular characterization and analyses [up to 2 years]

      investigate for possible biological markers for response, resistance and toxicity

    2. immunophenotyping or characterization of the immune cell subsets in the periphery [In biological samples collected at screening, visit 5/6, end-of-treatment, safety visit and first follow-up visit.]

      Investigate immunological responses.

    3. To investigate the role of PET/CT in early response evaluation [up to 2 years]

      PET-CT will be taken at predefined time-points for a subset of patients

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically confirmed NSCLC stage IIIB/IIIC or IV not amenable for curative treatment, with PD-L1 ≥ 50% measured by a validated method, and eligible for pembrolizumab monotherapy in the first-line setting

    • At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline according to RECIST 1.1

    • Subjects who received previous neo-adjuvant or adjuvant systemic therapy (other than immunotherapies) will be eligible if neo-adjuvant or adjuvant therapy was completed at least 12 months prior to the development of metastatic disease. Last dose of neoadjuvant or adjuvant therapy must be more than 12 months prior to enrollment/randomization

    • Available unstained archived tumour tissue sample in sufficient quantity to allow for analyses. At least fifteen unstained slides or a tumour block (preferred)

    • Male and female age ≥ 18 years at time of signing the ICF

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

    • Adequate organ function as defined below

    • Haemoglobin ≥9.0 g/dL

    • Absolute neutrophil count (ANC) 1.5 x (> 1500 per mm3)

    • Platelet count ≥100 x 109/L (>75,000 per mm3)

    • Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).

    • AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN

    • Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL >40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:

    Males:

    Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)

    Females:

    Creatinine CL (mL/min)

    = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)

    • Written informed consent obtained prior to any study specific procedure
    Exclusion Criteria:
    • Previous treatment with a PD-1 or PD-L1 inhibitor, including pembrolizumab or any other agent targeting immune checkpoints

    • Previous malignancy (except non-melanoma skin cancer and the following in situ cancers: bladder, gastric, esophageal, colon, endometrial, cervical, melanoma or breast) unless a complete remission was achieved at least 2 years prior to study entry

    • Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids (prednisone >10 mg or equivalent). Surgery, radiation and/or corticosteroids (any dose >10 mg prednisone equivalent) must have been completed ≥ 2 weeks prior to registration

    • Known history of leptomeningeal carcinomatosis

    • Uncontrolled seizures.

    • Current or prior use of immunosuppressive medication within 28 days before the first dose of pembrolizumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroid premedication given as prophylaxis for imaging contrast allergy should not be counted for this criterion

    • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome) within the past 2 years. Subjects with vitiligo, alopecia, Grave's disease, or psoriasis not requiring systemic treatment (within the past 3 years) are not excluded

    • History of primary immunodeficiency

    • History of allogeneic organ transplant

    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent

    • Active infection including tuberculosis (clinical evaluation including: physical examination findings, radiographic findings, positive PPD test, etc.), hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies as defined by a positive ELISA test). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. HIV testing is not required in the absence of clinical suspicion

    • Pregnant or lactating women

    • Live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving pembrolizumab

    • Any condition that, in the opinion of the investigator, would interfere with the evaluation of study treatment or interpretation of patient safety or study results

    • History of allergy or hypersensitivity to any of the active substances or excipients in the study drug

    • Involvement in the planning and/or conduct of the study (investigator staff and/or staff at the study site)

    • Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Vestre Viken Health Trust Drammen Viken Norway 3004

    Sponsors and Collaborators

    • Vestre Viken Hospital Trust
    • University Hospital, Akershus
    • Oslo University Hospital
    • Haukeland University Hospital
    • Helse Stavanger HF
    • Helse Fonna
    • Helse Nord-Trøndelag HF
    • St. Olavs Hospital
    • Alesund Hospital
    • Helse Forde
    • University Hospital of North Norway

    Investigators

    • Principal Investigator: Odd Terje Brustugun, MD, PhD, Vestre Viken Health trust

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Vestre Viken Hospital Trust
    ClinicalTrials.gov Identifier:
    NCT05344209
    Other Study ID Numbers:
    • LUNGVAC
    First Posted:
    Apr 25, 2022
    Last Update Posted:
    Aug 18, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 18, 2022