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)
- Conditions
- lung cancerNSCLC10038666
- Registration Number
- NL-OMON56303
- Lead Sponsor
- PDC*line Pharma SAS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 11
Pre-screening: Documented HLA-A*02:01 positivity and absence of anti-HLA
antibodies against HLA molecules expressed by the PDC*line, after the patient
has provided written informed consent.. Screening: 1.Patients with
histologically proven, or cytologically proven, 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. a.For the
dose-escalation phase (Cohorts A1 and A2): (i)Stage IIa/IIb/IIIa NSCLC
following radical surgery (R0 resection) and, if applicable, adjuvant
platinum-based chemotherapy, or (ii)Stage IV histologically or cytologically
confirmed case of epidermoid (squamous) lung cancer following 4 cycles 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 following 4 to 6 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 partial / complete response. b.For the anti-PD-1
immunotherapy (Cohorts B1, B2 and C1): -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.
Radiotherapy/chemoradiotherapy for prior stage III NSCLC is allowed if the
treatment-free interval is >1 year. 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 >= 70x10^9 /L; •White blood cell count >= 2.5 x 10^9 /L with
•lymphocytes >=1x10^9 /L at screening or at baseline , and •absolute neutrophil
count >=1.5x10^9/L, •Haemoglobin >= 90 g/L 5.Patient willing 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 or have been treated, •Subjects with symptomatic CNS metastases
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 provided. The patient agrees to use a highly effective
contraception method from signing informed consent form (screening
1.Mixed small-cell and non-small-cell histological features. 2.Patient has
previously 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. Chemoradiotherapy with consolidation durvalumab for
prior stage III disease. 4. Patient with Stage IV disease that received prior
radiotherapy (except palliative radiotherapy e.g. brain irradiation).
Palliative radiotherapy for stage IV disease should be completed one week prior
to baseline visit and for brain irradiation a 2-week window is required.
5.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). 6.Patient has a medical history of
cancer other than NSCLC, except the following: (i) non-melanoma skin cancer
with complete resection, (ii) adequately treated carcinoma in situ, (iii) other
cancer treated with no evidence of disease for at least five years with the
exception of pT1-2 prostatic cancer Gleason score < 6 and superficial bladder
cancer. 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. Patients with vitiligo, diabetes Type I,
psoriasis (not requiring psoralen plus ultraviolet A radiation, methotrexate,
retinoids, or oral corticosteroids within the previous 12 months) or a history
of autoimmune thyroiditis are not excluded.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint: Occurrence of dose-limiting toxicities (DLT) related to the<br /><br>administration of PDC*lung01.</p><br>
- Secondary Outcome Measures
Name Time Method