Clinical Trials Register

Summary
EudraCT Number:	2018-002382-19
Sponsor's Protocol Code Number:	PDC-LUNG-101
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2019-04-12
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2018-002382-19

A.3

Full title of the trial

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)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

PDC-LUNG-101

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	PDC*line Pharma SAS
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	PDC*line Pharma SAS
B.4.2	Country	France
B.4.1	Name of organisation providing support	PDC*line Pharma SA
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PDC*line Pharma SA
B.5.2	Functional name of contact point	Medical Director
B.5.3	Address:
B.5.3.1	Street Address	Avenue de l'hopital 11
B.5.3.2	Town/ city	Liège
B.5.3.3	Post code	4000
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+32477168163
B.5.6	E-mail	c.debruyne@pdc-line-pharma.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	PDC*lung01
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Unknown
D.3.9.1	CAS number	Unknown
D.3.9.2	Current sponsor code	PDC*lung01
D.3.9.4	EV Substance Code	SUB195402
D.3.10	Strength
D.3.10.1	Concentration unit	million organisms/ml million organisms/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	4.67 to 46.7
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	Yes
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Yes
D.3.11.3.5.1	CAT classification and reference number	PDC*vac; Somatic cell therapy medicinal product; Ref. EMA/556392/2015
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Non-small-cell lung cancer

E.1.1.1

Medical condition in easily understood language

Non-small-cell lung cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10061873
E.1.2	Term	Non-small cell lung cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assess safety and tolerability of PDC*lung01 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).

E.2.2

Secondary objectives of the trial

- Evaluate the safety of the combined use of PDC*lung01 with anti-PD-1 therapy
- Document additional indicators of safety / tolerability
- Evaluate the humoral allogeneic immune response against PDC*line cells
- Evaluate the specific T-cell response against the antigens borne by PDC*lung01 vaccine
- Document preliminary clinical activity in B2 cohort patients

E.2.3

Trial contains a sub-study

E.3

Principal 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-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 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 provided. 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 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.
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.

E.4

Principal 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 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.

E.5 End points

E.5.1

Primary end point(s)

Occurrence of dose-limiting toxicities (DLT) related to the administration of PDC*lung01

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline (Day 1/Week 1), D7, D14, D21, D28, D35 and D42

E.5.2

Secondary end point(s)

- 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
- Occurrence of serious adverse events (SAEs) and adverse events (AEs)
- Measurement of anti-HLA class I and II antibodies in the serum
- Ex vivo detection and characterization of CD8+ T cells against tumor antigens borne by PDC*lung01, using flow cytometry.
- Objective Response Rate (according to RECIST version 1.1) for cohort B2
- Objective Response Rate (according to iRECIST) for cohort B2
- Progression-Free Survival according to RECIST 1.1 and according to iRECIST for cohort B2

E.5.2.1

Timepoint(s) of evaluation of this end point

- Safety: Baseline (Day 1/Week 1), D7, D14, D21, D28, D35, D42 and D63
- Anti-HLA antibodies: Pre-screening, D7, D14, D21, D28, D42, D63 and if
applicable at M3,M6, M9, M12, M18 and M24
- Ex vivo detection of antigen specific CD8: Screening, D42, D63 and 10 weeks after the last dose
- ORR: Week 6, Week 10-12
- PFS: 9 months from the first day of anti-PD-1 antibody administration

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Dose-escalation design

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The End of Trial will occur when the last subject completes his last visit/contact of the 2 years-follow-up period.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-04-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-04-25

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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