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.
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.
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.
