Phase I/II Study on Safety, Tolerability, and Immunogenicity of PDC*lung01 with or without Anti-PD-1 Therapy in Non-Small-Cell Lung Cancer Patients
- Trial ID
- 2024-517429-24-00
- Protocol
- PDC-LUNG-101
- Sponsor
- PDC line pharma
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the **safety** and tolerability of PDC*lung01 vaccinations administered at two dose levels. This evaluation is conducted either as a single agent or in conjunction with maintenance treatment by pemetrexed for adenocarcinomas in Cohorts A1 and A2, or during treatment with anti-PD-1 therapy in Cohorts B1 and B2. The clinical relevance of this objective lies in determining the potential of PDC*lung01 as a therapeutic option for patients with non-small-cell lung cancer (NSCLC), ensuring that the treatment is both safe and tolerable for patients.
Secondary objectives include: - Evaluating the safety of the combined use of PDC*lung01 with anti-PD-1 therapy. - Documenting additional indicators of safety and tolerability. - Evaluating the humoral allogeneic immune response against PDC*line cells. - Evaluating the specific T-cell response against the antigens borne by the PDC*lung01 vaccine. - Documenting preliminary clinical activity. These objectives aim to provide a comprehensive understanding of the immunogenicity and preliminary clinical activity of the PDC*lung01 vaccine, further supporting its potential use in NSCLC treatment.
Participants
The clinical trial involves participants diagnosed with **non-small-cell lung cancer** (NSCLC), specifically targeting both male and female subjects aged 18 years and above. The study population includes individuals with histologically or cytologically confirmed NSCLC, with stages ranging from IIa to IV, as per the American Joint Committee on Cancer classification. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Selection criteria include adequate renal, hepatic, and hematological function, and participants must be willing to comply with study requirements, including providing informed consent. Lifestyle considerations such as diet or physical activity are not explicitly mentioned. The trial includes a vulnerable population, and participants must meet specific health insurance criteria if enrolled in France. Key inclusion criteria involve pre-screening for HLA-A*02:01 positivity and the absence of anti-HLA antibodies, as well as the ability to provide a baseline blood sample for immune monitoring. The trial does not provide additional lifestyle or demographic details beyond those specified in the inclusion criteria.
Plans and Procedures
The clinical trial is designed to evaluate the **safety**, tolerability, immunogenicity, and preliminary clinical activity of the therapeutic cancer vaccine, PDC*lung01, in patients with **non-small-cell lung cancer** (NSCLC). This is an open-label, dose-escalation, phase I/II study. The trial involves the administration of PDC*lung01 either as a single agent or in combination with anti-PD-1 therapy. The study is structured as a randomized, controlled trial with a double-blind design to ensure unbiased results. The trial is expected to conclude by December 31, 2025, with recruitment having commenced on September 10, 2019.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as documented HLA-A*02:01 positivity and absence of anti-HLA antibodies. Following successful screening, participants will be enrolled in one of the study cohorts. The trial includes multiple follow-up visits to monitor the occurrence of dose-limiting toxicities and adverse events, as well as to assess the immunogenic response through the detection and characterization of CD8+ T cells. The end-of-study visit will evaluate the overall response rate and progression-free survival.
The expected length of participant involvement varies depending on the cohort assignment and response to treatment, with the study treatment period extending until 28 days after the last dose of PDC*lung01. Conditions that may lead to early termination from the study include the occurrence of serious adverse events or the development of contraindications to the study medication. Participants are required to comply with study procedures and provide informed consent prior to any study-specific activities. The trial aims to provide valuable insights into the potential benefits of PDC*lung01 in treating NSCLC, contributing to the advancement of cancer immunotherapy.
Treatment
The clinical trial involves the administration of **PDC*lung01**, an advanced therapy investigational medicinal product (ATIMP) developed by PDC LINE PHARMA S.A.S. This experimental medication consists of **allogeneic plasmacytoid dendritic cells**, which are loaded with seven lung tumor antigen-derived peptides and subsequently irradiated. The pharmaceutical form of PDC*lung01 is an injection, and it can be administered via intravenous, subcutaneous, or intramuscular routes. The dosing schedule and frequency of administration are determined based on the specific cohort and treatment regimen within the trial. Participant compliance with the administration schedule is monitored throughout the study.
In addition to the experimental treatment, the study includes the administration of **pemetrexed**, marketed under the name ALIMTA, which is used as a standard-of-care therapy. Pemetrexed is available in two formulations: a 100 mg and a 500 mg powder for concentrate for solution for infusion, both produced by ELI LILLY NEDERLAND B.V. The active substance, pemetrexed, is a chemical compound administered via intravenous infusion. The dosing regimen for pemetrexed is aligned with standard clinical practice for the treatment of non-small-cell lung cancer (NSCLC) and is used in maintenance therapy for adenocarcinomas in specific cohorts.
Another non-experimental treatment used in the study is **pembrolizumab**, marketed as KEYTRUDA by MERCK SHARP & DOHME B.V. Pembrolizumab is a protein-based therapeutic agent, specifically a monoclonal antibody, administered as a concentrate for solution for infusion. The route of administration is intravenous infusion. Pembrolizumab is utilized in the trial as an anti-PD-1 therapy, and its dosing schedule is consistent with its approved use in the treatment of NSCLC. Compliance with pembrolizumab administration is monitored to ensure adherence to the protocol.
Efficacy
The efficacy of the therapeutic cancer vaccine, PDC*lung01, in patients with non-small-cell lung cancer (NSCLC) will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the occurrence of dose-limiting toxicities (DLT) related to the administration of PDC*lung01. Secondary endpoints include the occurrence of serious adverse events (SAEs) and adverse events (AEs) associated with the combination of PDC*lung01 and anti-PD-1 therapy, monitored during the study treatment and up to 28 days after the last dose of PDC*lung01. Additionally, the study will measure anti-HLA class I and II antibodies in the serum, with allelic specificity determined in cases of positive detection.
Further efficacy assessments involve the ex vivo detection and characterization of CD8+ T cells against tumor antigens presented by PDC*lung01 using flow cytometry. The study will also evaluate the Objective Response Rate (ORR) according to RECIST version 1.1 and iRECIST for cohort B2, as well as Progression-Free Survival (PFS) at 9 months from the first day of anti-PD-1 antibody administration, assessed by both RECIST 1.1 and iRECIST criteria. These endpoints will provide comprehensive data on the clinical activity and immunogenicity of PDC*lung01 in the specified patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Pre-screening: Documented HLA-A*02:01 positivity and absence of anti-HLA antibodies against HLA molecules expressed by the PDC*line (See protocol section 14.9.2), after the patient has provided written informed consent. Only patients meeting the above 2 criteria in pre-screening will be allowed to enter the screening period.
- 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 (see protocol section 24.1) a. For the dose-escalation phase (Cohorts A1 and A2): a period of at least 4 weeks after last SOC treatment administration/standard therapeutic intervention is required before first study dose administration: (i) Stage IIa/IIb/IIIa NSCLC following radical surgery (R0 resection) and, if applicable, following adjuvant platinum-based chemotherapy, or (ii) Stage IV histologically or cytologically confirmed case of epidermoid (squamous) lung cancer 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 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.
- ECOG performance status 0 or 1
- 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)
- Adequate haematological function as defined below: • Platelet count ≥ 70 × 109 /L; • White blood cell count ≥ 2.5 x 109 /L with lymphocytes ≥ 1 x 109 /L at screening or at baseline and absolute neutrophil count ≥ 1.5x109/L; • Haemoglobin ≥ 90 g/L
- 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)
- 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
- 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: − 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
- 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
- In the Investigator’s opinion, the patient is able and willing to comply with the requirements of the study
- Patient willing and able to sign the study informed consent form before any study-specific procedures are conducted
- Patient (male or female) is aged 18 years or above
- Specific for patients enrolled in France: Patient is affiliated to a health insurance system
Exclusion Criteria
- Mixed small-cell and non-small-cell histological features
- 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
- 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
- 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
- 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)
- 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
- Known hepatitis B and/or C infection (testing not required)
- Known positive for human immunodeficiency virus (HIV; testing not required)
- 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)
- Any history of splenectomy or splenic irradiation
- For female patients: pregnancy or lactation
- 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
- Specific for patients enrolled in France: Patient is under legal protection
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 10 Sept 2019 | 32 |
 France | Not Recruiting | 10 Sept 2019 | 10 |
 Germany | Not Recruiting | 10 Sept 2019 | 5 |
 The Netherlands | Not Recruiting | 10 Sept 2019 | — |
 Poland | Not Recruiting | 10 Sept 2019 | 7 |
| Netherlands | — | — | 10 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ALIMTA 500 mg powder for concentrate for solution for infusion | Other | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | — | — | PRD2433080 |
ALIMTA 100 mg powder for concentrate for solution for infusion | Other | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | — | — | PRD2426372 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Other | CONCENTRATE FOR SOLUTION FOR INFUSION | IV INFUSION | — | — | PRD4323105 |
PDC*lung01 | Test | INJECTION | INTRAVENOUS/SUBCUTANEOUS/INTRAMUSCULAR | — | — | PRD11542270 |
PDC*lung01 | Test | INJECTION | INTRAVENOUS/SUBCUTANEOUS/INTRAMUSCULAR | — | — | PRD11542269 |