Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03970746
Other study ID # PDC-LUNG-101
Secondary ID 2018-002382-19
Status Active, not recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date September 10, 2019
Est. completion date December 2025

Study information

Verified date October 2023
Source PDC*line Pharma SAS
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


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), a V7 one week after the last injection and an end-of-treatment (EoT) visit (V8, 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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 73
Est. completion date December 2025
Est. primary completion date December 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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) 1. (i) Stage IIa/IIb/IIIa NSCLC following radical surgery (R0 resection) and, if applicable, following adjuvant platinum-based chemotherapy (Figure 2) -, or (ii) Stage IV histologically or cytologically confirmed case of epidermoid (squamous) lung cancer following 4 cycles of platinum-based therapy (Figure 3), 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 (Figure 3), 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. 2. 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 = 70 x 10?/L; - White blood cell count = 2.5 x 10?/L with - lymphocytes = 1 x 10?/L, among which = 10 % of CD8+ T cells at screening or at baseline and - absolute neutrophil count = 1.5 x 10?/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 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. 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: 1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), 2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable). 3. Intrauterine device (IUD) 4. Intrauterine hormone-releasing system (IUS) 5. Monogamous relationship with a vasectomized partner. Partner must have been vasectomized for at least 6 months before the participant entered into the study 6. 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. 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) in situ carcinoma of the cervix, (iii) other cancer treated with no evidence of disease for at least five years. 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


Intervention

Biological:
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.
Drug:
Keytruda Injectable Product
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
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.

Locations

Country Name City State
Belgium Grand Hôpital de Charleroi Charleroi
Belgium Jessa Ziekenhuis Hasselt
Belgium AZ Groeninge Kortrijk
Belgium University Hospitals KU Leuven Leuven
Belgium CHU Liège- Sart Tilman Liège
Belgium AZ Delta vzw Roeselare
Belgium AZ Sint-Nikolaas Sint-Niklaas
France CHU Grenoble Grenoble
France Centre Léon Bérard, Centre de lutte contre le cancer Lyon
France CHU Nantes Nantes
Germany Universitätsklinikum Franlkfurt Frankfurt am main
Germany Kliniken der Stadt Köln GmbH Köln
Netherlands Jeroen Bosch Ziekenhuis - 's hertogenbosch 's Hertogenbosch
Netherlands Antoni Van Leeuwenhoek (Nederlands Kanker Instituut) Amsterdam
Netherlands Leiden University Medical Center (LUMC) Leiden
Poland University Clinical Centre Gdansk

Sponsors (1)

Lead Sponsor Collaborator
PDC*line Pharma SAS

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Netherlands,  Poland, 

Outcome

Type Measure Description Time frame Safety issue
Primary Occurrence of dose-limiting toxicities (DLT) related to the administration of PDC*lung01 Up to one week after the last injection (Day 42)
Secondary 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 Up to Day 63
Secondary Occurrence of serious adverse events (SAEs) and adverse events (AEs) Up to Day 63
Secondary Detection of anti-HLA class I and II antibodies in the serum Screening, Day 35 and Day 63
Secondary Ex vivo detection and characterization of CD8+ T cells against tumor antigens borne by PDC*lung01, using flow cytometry Screening, Day 35 and Day 63
Secondary Objective Response Rate (according to RECIST version 1.1 for cohorts A1/A2 and iRECIST for cohorts B1/B2) Day 63
Secondary Progression-Free Survival 9 months from the first day of platinum-based or anti-PD-1 antibody administration
See also
  Status Clinical Trial Phase
Recruiting NCT05094804 - A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents Phase 1/Phase 2
Recruiting NCT05707286 - Pilot Study to Determine Pro-Inflammatory Cytokine Kinetics During Immune Checkpoint Inhibitor Therapy
Recruiting NCT04258137 - Circulating DNA to Improve Outcome of Oncology PatiEnt. A Randomized Study N/A
Completed NCT01945021 - Phase II Safety and Efficacy Study of Crizotinib in East Asian Patients With ROS1 Positive, ALK Negative Advanced NSCLC Phase 2
Completed NCT04487457 - Prospective Study to Evaluate the Blood Kinetics of Immune Cells and Immunosuppressive Cytokines After Exposure to an Immunity Checkpoint Inhibitor (ICI): Study of the Impact of Chemotherapy
Terminated NCT04022876 - A Study of ALRN-6924 for the Prevention of Chemotherapy-induced Side Effects (Chemoprotection) Phase 1
Recruiting NCT05898763 - TEIPP Immunotherapy in Patients With NSCLC Phase 1/Phase 2
Recruiting NCT05532696 - Phase 1b/2 Study to Evaluate ABT-101 in Solid Tumor and NSCLC Patients Phase 1/Phase 2
Completed NCT04311034 - A Study of RC48-ADC in Subjects With Advanced Non-small Cell Lung Cancer Phase 1/Phase 2
Active, not recruiting NCT03177291 - Pirfenidone Combined With Standard First-Line Chemotherapy in Advanced-Stage Lung NSCLC Phase 1
Terminated NCT03257722 - Pembrolizumab + Idelalisib for Lung Cancer Study Phase 1/Phase 2
Completed NCT00349089 - Trial on Refinement of Early Stage Lung Cancer Adjuvant Therapy Phase 2
Completed NCT05116891 - A Phase 1/2 Study of CAN04 in Combination With Different Chemotherapy Regimens in Subjects With Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT04571632 - Clinical Trial of SBRT and Systemic Pembrolizumab With or Without Avelumab/Ipilimumab+ Dendritic Cells in Solid Tumors Phase 2
Terminated NCT03599518 - DS-1205c With Gefitinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer Phase 1
Not yet recruiting NCT06020989 - Lazertinib and Chemotherapy Combination in EGFR-mutant NSCLC Patients Without ctDNA Clearance After lead-in Lazertinib Monotherapy Phase 2
Withdrawn NCT03982134 - PDR001 + Panobinostat for Melanoma and NSCLC Phase 1
Withdrawn NCT03574649 - QUILT-2.024: Phase 2 Neoadjuvant, Consolidation, and Adjuvant Combination NANT Immunotherapy Versus Standard of Care in Subjects With Resectable Non-small Cell Lung Cancer Phase 2
Withdrawn NCT02844140 - DE-CT in Lung Cancer Proton Therapy N/A
Terminated NCT02628535 - Safety Study of MGD009 in B7-H3-expressing Tumors Phase 1

External Links