Safety, immunogenicity and preliminary clinical activity study of PDC*lung01 cancer vaccine in NSCLC

Phase 1

Conditions: Therapeutic area: Diseases [C] - Cancer [C04]
on-small-cell lung cancer
MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2018-002382-19-DE

Lead Sponsor: PDC*line Pharma SAS

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 64

Inclusion Criteria

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-smallcell 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, or
(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 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. 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 required. The patient agrees to use a 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

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 (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 has been receiving a dose of systemic corticosteroid exceeding 10mg during the screening period.
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.
13. Specific for patients enrolled in France: Patient is under legal protection.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Assess safety and tolerability of PDClung01 vaccinations administered at two dose levels as single agent or during maintenance treatment by pemetrexed (for adenocarcinomas in Cohorts A1 and A2) or during treatment with anti-PD-1 therapy (Cohorts B1 and B2).;Secondary Objective: - Evaluate the safety of the combined use of PDClung01 with anti-PD-1 therapy<br>- Document additional indicators of safety / tolerability<br>- Evaluate the humoral allogeneic immune response against PDCline cells<br>- Evaluate the specific T-cell response against the antigens borne by PDClung01 vaccine<br>- Document preliminary clinical activity in B2 cohort patients ;Primary end point(s): Occurrence of dose-limiting toxicities (DLT) related to the administration of PDC*lung01 ;Timepoint(s) of evaluation of this end point: Baseline (Day 1/Week 1), D7, D14, D21, D28, D35 and D42

Secondary Outcome Measures

Name	Time	Method

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