Clinical Trials /

Safety, Immunogenicity and Preliminary Clinical Activity Study of PDC*lung01 Cancer Vaccine in NSCLC

NCT03970746

Description:

PDC-LUNG-101 trial is an open-label, dose-escalation, phase I/II study to assess the safety, the tolerability, the immunogenicity and the preliminary clinical activity of the therapeutic cancer vaccine, PDC*lung01, associated or not with anti-PD-1 treatment in patients with non-small-cell lung cancer.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety, Immunogenicity and Preliminary Clinical Activity Study of PDC*lung01 Cancer Vaccine in NSCLC
  • Official Title: An Open-label, Dose-escalation, Phase I/II Study to Assess the Safety, the Tolerability, the Immunogenicity and the Preliminary Clinical Activity of the Therapeutic Cancer Vaccine, PDC*lung01, Associated or Not With Anti-PD-1 Treatment in Patients With Non-small-cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: PDC-LUNG-101
  • SECONDARY ID: 2018-002382-19
  • NCT ID: NCT03970746

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
PDC*lung01Cohort A1
Keytruda Injectable ProductPembrolizumabCohort B1
Alimta Injectable ProductPemetrexedCohort A1

Purpose

PDC-LUNG-101 trial is an open-label, dose-escalation, phase I/II study to assess the safety, the tolerability, the immunogenicity and the preliminary clinical activity of the therapeutic cancer vaccine, PDC*lung01, associated or not with anti-PD-1 treatment in patients with non-small-cell lung cancer.

Detailed Description

      The therapeutic cancer vaccine, PDC*lung01 will be administered at two dose levels (low dose
      (LD) and high dose (HD)), as single agent or during maintenance treatment by pemetrexed (for
      adenocarcinomas in Cohorts A1 and A2) or added to the SoC (cohorts B1 and B2) i.e. anti-PD-1.

      In cohorts A1 (low dose cohort) and A2 (high dose cohort), NSCLC patients will be treated at
      each of the six PDC*lung01 treatment visits with low dose/high dose administered successively
      by subcutaneous and then by intravenous route.

      In cohort B1 and B2, the first PDC*lung01 injection will start within 48 hours after the
      first infusion of anti-PD-1. The fourth PDC*lung01 injection will occur within 48 hours after
      the infusion of the second cycle of anti-PD-1.

      For each patient, the study will be divided into three consecutive parts:

        -  Pre-screening (for HLA-A*02:01 positivity), only patients with positive HLA-A*02:01
           status will be proposed to be screened.

        -  Active period comprising a screening period, a treatment period (visits V1 to V6, during
           which the patient receives PDC*lung01 vaccine, at each visit) and an end-of-treatment
           (EoT) visit (V7, 4 weeks after the last injection),

        -  Follow-up period which starts after the EoT visit and lasts up to two years after the
           first IMP administration.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort A1ExperimentalPDC*lung01 Low Dose
  • PDC*lung01
  • Alimta Injectable Product
Cohort A2ExperimentalPDC*lung01 High Dose
  • PDC*lung01
  • Alimta Injectable Product
Cohort B1ExperimentalPDC*lung01 Low Dose added to SoC, i.e., anti-PD-1 treatment
  • PDC*lung01
  • Keytruda Injectable Product
Cohort B2ExperimentalPDC*lung01 High Dose added to SoC, i.e., anti-PD-1 treatment
  • PDC*lung01
  • Keytruda Injectable Product

Eligibility Criteria

        Inclusion criteria:

        Pre-screening:

        Documented HLA-A*02:01 positivity after the patient has provided written informed consent.

        Only patients showing a documented positive result in pre-screening will be allowed to
        enter the screening period.

        Screening:

          1. Patients with histologically proven, or cytologically proven (allowed only for
             patients recruited in cohorts A1/A2), non-small-cell lung cancer (NSCLC). The stage of
             the disease is evaluated according to the classification of the American Joint
             Committee on Cancer, 8th edition (see Section 25.1)

             a. For the dose-escalation phase (Cohorts A1 and A2): a wash-out period of at least 4
             weeks after administration of the last cycle of platinum-based chemotherapy is
             required.

             (i) Stage IIa/IIb/IIIa NSCLC following surgery and, if applicable, following adjuvant
             platinum-based chemotherapy, or (ii) Stage IV histologically or cytologically
             confirmed case of epidermoid (squamous) NSCLC following 4 courses of platinum-based
             therapy, or (iii) Stage IV histologically or cytologically confirmed case of
             adenocarcinoma (non-squamous) lung cancer NSCLC following 4 to 6 courses cycles of
             pemetrexed and platinum combination, (iv) Populations (ii) and (iii) who have stopped
             prematurely chemotherapy, after at least 2 cycles of platinum-based therapy, for any
             reason, AND do present with a documented stable disease or complete response.

             b. For the anti-PD-1 immunotherapy (Cohorts B1 and B2):

             - The patient has first-line metastatic stage IV NSCLC disease and is starting
             anti-PD-1. The intention and decision to prescribe the anti-PD-1 monotherapy as SoC
             (TPS≥50%) must have been made by the investigator before and regardless of the
             patient's participation in the study.

          2. ECOG performance status 0 or 1.

          3. Adequate renal and hepatic function as defined below:

               -  Serum creatinine clearance > 50 mL/min (Cockcroft-Gault formula)

               -  Bilirubin ≤ 1.5 times upper limit of normal (ULN)

               -  Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times ULN (up
                  to 5 times ULN are allowed in case of presence of liver metastases).

          4. Adequate haematological function as defined below:

               -  Platelet count ≥ 70 x 10⁹/L;

               -  White blood cell count ≥ 2.5 x 10⁹/L with

               -  lymphocytes ≥ 1 x 10⁹/L, among which ≥ 10 % of CD8+ T cells and

               -  absolute neutrophil count ≥ 1.5 x 10⁹/L;

               -  Haemoglobin ≥ 90 g/L

          5. Patient willing and able to provide a baseline blood sample for leucocyte enumeration,
             cellular allogeneic response and immune-monitoring of 100 ml in total (in one or two
             samplings).

          6. For patients with brain metastases:

               -  Central nervous system metastases are not symptomatic and have been treated,

               -  In addition, subjects must be either off corticosteroids, or on a stable or
                  decreasing dose of ≤10mg daily prednisone (or equivalent) during at least 2 weeks
                  before baseline.

          7. For female patients without child-bearing potential: a documentation of tubal ligation
             or hysterectomy, ovariectomy or a post-menopausal status is available.

             For female patients of child-bearing potential: a negative serum pregnancy test at
             screening is required. The patient agrees to practice a "dual method" contraception
             from signing informed consent form (screening), throughout the study treatment period
             with PDC*lung01 and for at least 28 days after the last administration of PDC*lung01.

             For female patients receiving Pemetrexed in cohorts A1/A2 concomitantly with
             PDC*lung01, according to corresponding SmPC, it is required to use effective
             contraception during treatment with pemetrexed.

             For female patients receiving Pembrolizumab in cohorts B1/B2 concomitantly with
             PDC*lung01, according to corresponding SmPC, it is required to use an effective method
             of contraception up to 4 months thereafter.

             A woman is considered of childbearing potential (WOCBP), i.e. fertile, following
             menarche and until becoming post-menopausal unless permanently sterile. Permanent
             sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral
             oophorectomy.

             A postmenopausal state is defined as no menses for 12 months without an alternative
             medical cause.

             "Dual method" contraception is defined as the use of at least 2 methods among the
             following:

               -  Hormonal contraception (such as oral, injection, transdermal patch, implant)

               -  Barrier (condom with spermicide or diaphragm with spermicide) during intercourse

               -  Intrauterine device

               -  Monogamous relationship with vasectomized partner.

               -  Abstinence or absence of sexual relations

          8. Males with reproductive potential should use barrier method of contraception (condom)
             from signing informed consent form (screening) up to at least 28 days after the last
             dose of PDC*lung01.

             For male patients receiving Pemetrexed in cohorts A1/A2 concomitantly with PDC*lung01,
             according to corresponding SmPC, it is required to use barrier method of contraception
             up to 6 months thereafter.

          9. In the Investigator's opinion, the patient is able and willing to comply with the
             requirements of the study.

         10. Patient willing and able to sign the study informed consent form before any
             study-specific procedures are conducted.

         11. Patient (male or female) is aged 18 years or above.

         12. Specific for patients enrolled in France : Patient is affiliated to a health insurance
             system.

        Exclusion criteria:

          1. Mixed small-cell and non-small-cell histological features.

          2. Patient has previously documented evidence of EGFR mutation, ALK fusion or ROS1 fusion
             (Cohorts B1 and B2). If unable to provide documentation of these molecular changes, an
             archival formalin-fixed paraffin-embedded tumour tissue should be submitted for
             testing.

          3. Patient has received immunotherapy or any investigational drugs within 4 weeks before
             the first PDC*lung01 dose.

          4. Patient without brain metastases has been receiving systemic corticosteroids at any
             dose for a period longer than 10 days before baseline (administration by nasal spray,
             topical solution or oral inhaler is non-systemic and is therefore allowed).

          5. Patient has a medical history of cancer other than NSCLC, except the following: (i)
             non-melanoma skin cancer with complete resection, (ii) in situ carcinoma of the
             cervix, (iii) other cancer treated with no evidence of disease for at least five
             years.

          6. Patient presents at screening anti-HLA antibodies against HLA molecules expressed by
             the PDC*line.

          7. Known hepatitis B and/or C infection (testing not required).

          8. Known positive for human immunodeficiency virus (HIV; testing not required).

          9. Uncontrolled congestive heart failure or hypertension, unstable heart disease
             (coronary artery disease with unstable angina or myocardial infarction within 6 months
             of baseline) or uncontrolled ventricular arrhythmias at the time of enrolment in the
             study (atrial fibrillation or flutter is acceptable).

         10. Any history of splenectomy or splenic irradiation.

         11. For female patients: pregnancy or lactation.

         12. Any condition, including autoimmune or immunodeficiency active disease that, in the
             opinion of the Investigator, would jeopardise patient's safety, or might compromise
             the effect of the study drug or the assessment of the study result.

         13. Specific for patients enrolled in France: Patient is under legal protection.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Occurrence of dose-limiting toxicities (DLT) related to the administration of PDC*lung01
Time Frame:Up to one week after the last injection (Day 42)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Occurrence of serious adverse events (SAEs) and adverse events (AEs), deemed as related to the association of PDC*lung01 and the anti-PD-1 therapy
Time Frame:Up to Day 63
Safety Issue:
Description:
Measure:Occurrence of serious adverse events (SAEs) and adverse events (AEs)
Time Frame:Up to Day 63
Safety Issue:
Description:
Measure:Detection of anti-HLA class I and II antibodies in the serum
Time Frame:Screening, Day 35 and Day 63
Safety Issue:
Description:
Measure:Ex vivo detection and characterization of CD8+ T cells against tumor antigens borne by PDC*lung01, using flow cytometry
Time Frame:Screening, Day 35 and Day 63
Safety Issue:
Description:
Measure:Objective Response Rate (according to RECIST version 1.1 for cohorts A1/A2 and iRECIST for cohorts B1/B2)
Time Frame:Day 63
Safety Issue:
Description:
Measure:Progression-Free Survival
Time Frame:9 months from the first day of platinum-based or anti-PD-1 antibody administration
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:PDC*line Pharma SAS

Trial Keywords

  • Anti-PD-1

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