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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT03970746

Studienbeginn:
September 2019

Letztes Update:
17.11.2020

Wirkstoff:
PDC*lung01, Keytruda Injectable Product, Alimta Injectable Product

Indikation (Clinical Trials):
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
PDC*line Pharma SAS

Collaborator:
-

Studienleiter

Johan Vansteenkiste, Prof
Principal Investigator
KU Leuven

Kontakt

Studienlocations (3 von 16)

AZ Delta vzw
8800 Roeselare
BelgiumRekrutierend» Google-Maps
Ansprechpartner:
Ingel Desmedts, MD
E-Mail: ingel.demedts@azdelta.be

Melissa Masschelin, Mrs.
E-Mail: Melissa.Masschelin@azdelta.be
» Ansprechpartner anzeigen
Assistance Publique Hôpitaux de Marseille, Centre d'essais précoces en cancérologie de Marseille (CEPCM)
13005 Marseille
FranceRekrutierend» Google-Maps
Ansprechpartner:

Phone: +33 4 91 38 84 77
» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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, if targeted treatment options were not indicated 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 if

targeted treatment options were not indicated, (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 measurable disease and is starting anti-PD-1. The intention

and decision to prescribe the anti-PD-1 monotherapy as SoC (TPS≥50%), assuming no

targeted mutation detected, following standard NGS testing, if applicable, and thus no

targeted treatment option is indicated, 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 practiceuse a "dual method"highly

effective contraception method 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.

"Highly effective" contraceptive measures acceptable for the whole duration of the

study have been defined based on the CTFGs recommendations on contraception and are

the following:

- Combined (estrogen and progestogen containing) hormonal contraception associated

with inhibition of ovulation (oral, intravaginal, transdermal),

- Progestogen-only hormonal contraception associated with inhibition of ovulation

(oral, injectable, implantable).

- Intrauterine device (IUD)

- Intrauterine hormone-releasing system (IUS)

- Monogamous relationship with a vasectomized partner. Partner must have been

vasectomized for at least 6 months before the participant entered into the study

- Abstinence or absence of sexual relations with men.

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 documented evidence of EGFR mutation, ALK fusion or ROS1 fusion (according

to current ESMO clinical practice guidelines) or any mutation for which targeted

treatment options would be indicated, as per SoC.

3. Patient has received immunotherapy or any investigational drugs within 4 weeks before

the first PDC*lung01 dose.

4. Patient without brain metastasis is receiving systemic corticosteroids at a dose level

exceeding 10 mg/day (prednisone or equivalent) during the screening period

(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.

Studien-Rationale

Primary outcome:

1. 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))



Secondary outcome:

1. 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)

2. Occurrence of serious adverse events (SAEs) and adverse events (AEs) (Time Frame - Up to Day 63)

3. Detection of anti-HLA class I and II antibodies in the serum (Time Frame - Screening, Day 35 and Day 63)

4. 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)

5. Objective Response Rate (according to RECIST version 1.1 for cohorts A1/A2 and iRECIST for cohorts B1/B2) (Time Frame - Day 63)

6. Progression-Free Survival (Time Frame - 9 months from the first day of platinum-based or anti-PD-1 antibody administration)

Studien-Arme

  • Experimental: Cohort A1
    PDC*lung01 Low Dose
  • Experimental: Cohort A2
    PDC*lung01 High Dose
  • Experimental: Cohort B1
    PDC*lung01 Low Dose added to SoC, i.e., anti-PD-1 treatment
  • Experimental: Cohort B2
    PDC*lung01 High Dose added to SoC, i.e., anti-PD-1 treatment

Geprüfte Regime

  • PDC*lung01:
    PDC*lung01 includes, in similar proportion, seven active agents, made of irradiated human plasmacytoid dendritic cells (PDC) loaded separately with a distinct synthetic peptide encoded by a lung tumor antigen, namely NY-ESO-1, MAGE-A3, MAGEA4, Multi-MAGE (an epitope common to several MAGE-A antigens), SURVIVN, MUC1 or a peptide derived from the Melan-A antigen.
  • Keytruda Injectable Product (Pembrolizumab):
    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.
  • Alimta Injectable Product (Pemetrexed):
    For patients with non-squamous NSCLC included in Cohorts A1 and A2, maintenance by pemetrexed (IV every 3 weeks) can be administered according to SoC.

Quelle: ClinicalTrials.gov


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