PDCline Pharma announced primary clinical results from its phase I/II trial of PDClung01, a cancer vaccine, in combination with pembrolizumab for stage IV Non-Small Cell Lung Cancer (NSCLC) patients with PD-L1 expression ≥ 50%. The data, presented at the European Society for Medical Oncology – Immuno-Oncology Congress 2024 (ESMO-IO 2024), indicate a promising anti-tumor response and a manageable safety profile.
The phase I/II trial (PDC-LUNG-101, NCT03970746) assessed the safety, tolerability, immunogenicity, and preliminary clinical activity of PDClung01 in NSCLC patients. The trial involved 67 evaluable HLA-A02:01 positive NSCLC patients across 17 European clinical sites. PDClung01 was administered weekly via subcutaneous and intravenous routes for six weeks. The study included two cohorts: patients receiving PDClung01 as a single agent in the adjuvant setting for stage II & IIIa NSCLC, and patients receiving PDC*lung01 combined with pembrolizumab for first-line stage IV NSCLC with PD-L1 ≥ 50%.
Key Findings from the Phase I/II Trial
The primary analysis focused on 42 evaluable patients in the B2 cohort (high dose PDC*lung01 with pembrolizumab) who reached a 9-month follow-up. The median follow-up was 19.5 months (95% CI 13.8-25.6).
- Objective Response Rate (ORR): The confirmed ORR was 55% (80% CI 43.7%; 65.4%), surpassing the trial's predefined success criterion of a 15% absolute increase compared to pembrolizumab alone (KEYNOTE-042, 39%).
- Progression-Free Survival (PFS): The median PFS was 8.9 months, representing a 36% relative improvement compared to KEYNOTE-042 (+2.4 months increase).
- Disease Control Rate (DCR): The DCR was 76% (80% CI: 83.8, 65.4), and the Clinical Benefit Rate (CBR) was 64%.
- Immune Response: 56% of patients demonstrated a tumor antigen-specific and effector memory CD8+ T-cell response. A significant correlation was observed between the amplitude of antigen-specific CD8+ T-cell response and PFS in patients without primary resistance to pembrolizumab.
- Safety Profile: The high dose of PDC*lung01 exhibited a mild safety profile. Most Treatment Emergent Adverse Events (TEAEs) were grades 1-2, with only one grade 4 related TEAE. Only 2% of related TEAEs led to discontinuation, compared to 9.1% for pembrolizumab alone in KEYNOTE-042.
Expert Commentary
"PDC*lung01 in combination with anti-PD-1 showed a very promising and durable response as well as a significant immune response in the last cohort of patients of the phase I/II trial with indications of a relationship with clinical outcome in cohort B2. The data suggest that this combination could offer a clinically meaningful tumor response in stage IV NSCLC patients, along with a compelling safety profile," said Prof Johan Vansteenkiste, emeritus professor in respiratory oncology at KU Leuven in Belgium and chair of the Data and Safety Monitoring Board (DSMB).
Future Directions
PDC*line Pharma plans to present further data at the end of 2025, after all patients have reached two years of follow-up. Based on these results, the company is preparing a randomized phase IIb study in untreated stage IV NSCLC (PD-L1 ≥50%) in combination with pembrolizumab, with initiation planned in 2026.
"We are thrilled by these promising results, which position PDClung01 as the first cancer vaccine of its kind tested in metastatic NSCLC with high PD-L1 expression," said Eric Halioua, CEO of PDCline Pharma. "Its unique mechanism of action and favorable safety profile make it an excellent complement to pembrolizumab and other existing or emerging therapies for this patient population."
