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

Phase 1/2

Active, not recruiting

• Conditions: Non-small-cell lung cancer

• Registration Number: 2024-517429-24-00
• Lead Sponsor: PDC line pharma

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-10-29
• Last Update Posted: 2025-06-17

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 64

Inclusion Criteria

Pre-screening: Documented HLA-A02:01 positivity and absence of anti-HLA antibodies against HLA molecules expressed by the PDCline (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.

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

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 PDClung01 and for at least 28 days after the last administration of PDClung01. For female patients receiving Pemetrexed in cohorts A1/A2 concomitantly with PDClung01, 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 PDClung01, 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 PDClung01. For male patients receiving Pemetrexed in cohorts A1/A2 concomitantly with PDClung01, according to corresponding SmPC, it is required to use barrier method of contraception up to 6 months thereafter

Exclusion Criteria

Mixed small-cell and non-small-cell histological features

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

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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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, monitored during study treatment until 28 days after the last dose of PDC*lung01		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, monitored during study treatment until 28 days after the last dose of PDC*lung01
Occurrence of serious adverse events (SAEs) and adverse events (AEs), monitored during study treatment until 28 days after the last dose of PDC*lung01		Occurrence of serious adverse events (SAEs) and adverse events (AEs), monitored during study treatment until 28 days after the last dose of PDC*lung01
Measurement of anti-HLA class I and II antibodies in the serum. In case of positive detection, the allelic specificity of the antibodies will be determined		Measurement of anti-HLA class I and II antibodies in the serum. In case of positive detection, the allelic specificity of the antibodies will be determined
Ex vivo detection and characterization of CD8+ T cells against tumor antigens borne by PDC*lung01, using flow cytometry		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 RECIST version 1.1) for cohort B2
Objective Response Rate (according to iRECIST) for cohort B2		Objective Response Rate (according to iRECIST) for cohort B2
Progression-Free Survival at 9 months according to RECIST 1.1 and according to iRECIST from the first day of anti-PD-1 antibody administration for cohort B2		Progression-Free Survival at 9 months according to RECIST 1.1 and according to iRECIST from the first day of anti-PD-1 antibody administration for cohort B2

Trial Locations

Locations (10)

Algemeen Ziekenhuis Groeninge; 🇧🇪 Kortrijk, Belgium

Algemeen Ziekenhuis Delta; 🇧🇪 Roeselare, Belgium

Jessa Ziekenhuis; 🇧🇪 Hasselt, Belgium

Centre Leon Berard; 🇫🇷 Lyon, France

Hôpitaux Universitaires de Marseille Timone; 🇫🇷 Marseille, France

Kliniken der Stadt Koeln gGmbH; 🇩🇪 Cologne, Germany

Uniwersyteckie Centrum Kliniczne; 🇵🇱 Gdansk, Poland

Jeroen Bosch Ziekenhuis Stichting; 🇳🇱 'S-Hertogenbosch, Netherlands

Leids Universitair Medisch Centrum (LUMC); 🇳🇱 Leiden, Netherlands

Netherlands Cancer Institute; 🇳🇱 Amsterdam, Netherlands

Algemeen Ziekenhuis Groeninge

🇧🇪Kortrijk, Belgium

Sofie Derijcke

Site contact

003256633340

SOFIE.DERIJCKE@azgroeninge.be