LIÈGE, Belgium and GRENOBLE, France–(COMMERCIAL THREAD)–PDC*line Pharma, a clinical-stage biotechnology company developing a new class of potent and scalable active immunotherapies for cancer, today announces the first immunology results from its Phase I/II clinical trial PDC-LUNG-101 (NCT03970746) with PDC *lung01, the company’s standard therapeutic cancer vaccine candidate for non-small cell lung cancer (NSCLC). The preliminary data was presented today in a poster session at the ESMO Congress of Immuno-Oncology 2022 (ESMO-IO) in Geneva (Switzerland). The results showed that in a large percentage of subjects PDC*lung01, in monotherapy and in combination with pembrolizumab, induces a significant expansion of effector memory CD8+ T cells specific for tumor peptides carried by PDC*lung01.
The objectives of the phase I/II study (PDC-LUNG-101) are to evaluate the safety, tolerability, immunogenicity and preliminary clinical activity of the drug candidate PDC*lung01, associated or not with anti-PD-1 treatment in patients with NSCLC. PDC*lung01 will be administered to a total of 64 patients with evaluable HLA-A*02:01 positive NSCLC, at two dose levels in two different settings:
As a single agent for patients in the adjuvant setting (A1: low dose, A2: high dose)
Addition to standard of care anti-PD-1 monotherapy for patients with first-line stage IV (metastatic) NSCLC with a PD-L1 tumor proportion score ≥50% and no targetable driver mutation (B1: low dose, B2: high dose)
PDC*lung01 consists of irradiated human plasmacytoid dendritic cells (PDC* line), loaded with HLA-A*02:01-restricted peptides, derived from NY-ESO-1, MAGE-A3, MAGE-A4, Multi- MAGE- Tumor antigens A, MUC1 and Survivin. It is administered weekly subcutaneously and intravenously, in six consecutive doses. The safety and clinical activity of the product were presented at ESMO 2022 in September 2022 in Paris (France). The PDC* line is a potent professional antigen-presenting cell line which is capable of priming and potentiating the patient’s anti-tumor cytotoxic CD8+ T cells and is synergistic in vitro with anti-programmed death-1 (PD-1) treatment. The poster presented the analysis of the immune responses of the first three patient cohorts.
“We are very pleased that PDC*lung01 was found to be biologically active to trigger an anti-tumor immune response, detectable without any in vitro restimulation, in a significant number of patients in our NSCLC clinical trial. The first sign of correlation between immune and clinical responses in six metastatic patients from cohort B1 is encouraging.” said Dr. Joël Plumas, co-founder and scientific director of PDC*line Pharma.
“The presentation of the first immunology dataset of our lead candidate, PDC*lung01, for the treatment of NSCLC at ESMO-IO, a leading immuno-oncology conference, is an important milestone for the company,” he added. Eric Halioua, CEO of PDC*line Pharma. “We are very pleased to demonstrate that our innovative immunotherapy platform can induce a strong immune response in humans. These early results illustrate the potential targeted mechanism of action of PDC*lung01 to prime anti-tumor specific naïve T cells and activate effector memory T cells in humans.
Highlights of the poster exhibition
Poster title: The therapeutic cancer vaccine PDC*lung01 induces immune responses with or without anti-PD-1 treatment in patients with non-small cell lung cancer.
- Several circulating immune parameters were monitored at different times before and after PDC*lung01 administrations using tests developed by PDC*line Pharma
WBC count and determination of peptide-specific CD8+ T cells, for which a limit of quantification (LOQ) was defined to better assess fold changes of cell expansion. The tests allow for the assessment of circulating anticancer-specific CD8+ T cells before and after treatment, ex vivo with an unprecedented LOQ of 0.003%. in vitro restimulation
- PDC*lung01 iIt has been found to be biologically active in triggering an anti-tumor immune response in a significant number of patients
23 of the 25 included patients received at least four doses and were evaluable. No major changes in the frequencies of circulating lymphocytes (B cells, NK cells, CD4+, CD8+ T cells or Tregs) were observed during treatment. In contrast, a specific and memory CD8+ T cell response was induced against the antigens from which the peptides loaded on PDC*lung01 are derived in 33%, 45%, and 67% of evaluable patients, respectively, in A1 (six patients), Cohorts A2 (eleven patients) and B1 (six patients).
- First signal of correlation observed between immune response and best overall clinical response in metastatic patients treated with pembrolizumab
The best overall response in six evaluable patients from cohort B1, by RECIST criteria, included four partial responses, one stable disease, and one progressive disease. CD8+ T cells for at least one of six lung antigens were observed in most patients with partial and stable disease. In contrast, no immune response was detected in the patient with progressive disease
The poster is available here.
Information about PDC*line Pharma technology
The biological characteristics of the PDC* line offer unique advantages:
A professional antigen presenting cell line, much more potent than conventional dendritic cells in the initiation and expansion of antitumor-specific cytotoxic CD8+ T cells (conventional tumor antigens and neoantigens)
Although allogeneic, the PDC* line can be injected multiple times to boost the immune response
Easily produced on a large scale, with a fully controlled and simple manufacturing process (through the use of bioreactors with a synthetic medium without growth, differentiation or activation factors)
Easy to use: After thawing, the same standard product is used to treat the entire target population with a cancer type expressing the target antigens
Very versatile: Tumor antigens can be delivered by peptide loading, mRNA transfection or transduction of PDC line retroviruses*, and the target population can be extended beyond HLA-A2, (currently used as expressed by 50% of the Caucasian population), using other HLAs, already expressed by the PDC* line or added by genetic modification. In addition, new candidates can be validated for new cancer indications within weeks, with ex vivo test using human peripheral blood mononuclear cells (PBMCs)
It synergizes with anti-PD-1 to activate anti-tumor CD8 T cells
About PDC*line Pharma
Founded in 2014 as a spin-off of the French blood bank (EFS), PDC*line Pharma is a Franco-Belgian biotechnology company developing an innovative class of active cancer immunotherapies, based on a GMP grade allogeneic cell line of plasmacytoid dendritic cells (PDC* line). The PDC* line is significantly more potent than conventional dendritic cell-based vaccines in the priming and potentiation of antitumor antigen-specific cytotoxic T cells, including neoantigen-specific T cells, and is synergistic with checkpoint inhibitors. The technology can potentially be applied to any type of cancer. Following an initial Phase I human feasibility study in melanoma, PDC*line Pharma is focused on the development of PDC*lung01, a candidate for non-small cell lung cancer (NSCLC) currently in Phase I studies/ II, and PDC *neo with neoantigens in preclinical development. The company has a staff of 32 people, with an experienced management team. It has raised more than €56 million in equity and non-dilutive financing. In March 2019, PDC*line Pharma granted an exclusive license to LG Chem Life Sciences company in South Korea and an exclusive option in other Asian countries, for the development and commercialization of the lung cancer vaccine PDC*lung01. The total deal is worth €108 million, plus royalties on net sales in Asia.