On December 12, 2024 PDC*line Pharma, a clinical-stage biotech company developing a new class of immunotherapies for cancers, reported the primary results of its phase I/II clinical trial for PDC*lung01, an innovative off-the-shelf therapeutic cancer vaccine, at the ESMO (Free ESMO Whitepaper)-IO 2024 conference (Press release, PDC Line Pharma, DEC 12, 2024, View Source [SID1234649095]). PDC*lung01, when combined with pembrolizumab, demonstrated significant clinical benefits for stage IV Non-Small Cell Lung Cancer (NSCLC) patients with PD-L1 ≥ 50%, along with a mild safety profile.
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"PDC*lung01 in combination with anti-PD-1 showed a very promising and durable response as well as a significant immune response 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.
The phase I/II trial (PDC-LUNG-101, NCT03970746) evaluated the safety, tolerability, immunogenicity, and preliminary clinical activity of PDC*lung01 in NSCLC patients. The trial included 67 HLA-A02:01-positive NSCLC patients across five European countries. Patients received six weekly doses of PDC*lung01 through subcutaneous and intravenous administration. It assessed the vaccine in two doses both as a single agent (cohorts A1, A2 for stage II & IIIa NSCLC) and in combination with pembrolizumab (cohorts B1, B2 for stage IV NSCLC). Key clinical activity parameters, such as ORR and PFS, were analyzed in the B1 and B2 cohorts, with primary results reported from the high-dose, B2 cohort. With a database cut-off date on July 18, 2024, the patients’ median follow-up was 19.5 months (95% CI 13.8-25.6).
Highlights: View Source
Immune Response:
56% of patients exhibited tumor antigen-specific CD8+ T-cell responses, with measurable expansions of anti-tumor CD8+ T-cells observed in some cases, up to 2.3% of total CD8+T-cells.
A significant correlation was observed between the amplitude of antigen-specific CD8+ T-cell responses and PFS.
Efficacy:
In the high-dose (B2) cohort consisting of 42 evaluable patients, PDC*lung01 combined with pembrolizumab achieved a confirmed objective response rate (ORR) of 55% (80% CI 43.7%; 65.4%), surpassing the trial’s predefined success criteria (15% absolute increase compared to 39% for external comparator KEYNOTE-042). The Best Overall Response (BOR) according to RECIST 1.1 included 23 confirmed Partial Response (55%) and 12 Stable Disease (29%).
Median progression-free survival (mPFS) was 8.9 months, a 36% improvement (2.4 months longer) compared to pembrolizumab alone (KEYNOTE-042).
The Disease Control Rate (DCR) was 76% (80% CI: 83.8, 65.4) and Clinical Benefit Rate (CBR) was 64%. The 9-month PFS rate was 50% (80% CI 39.1%; 60.9%). Median duration of response and median overall survival were not reached.
Safety:
In 48 patients who received at least one dose of PDC*lung01 in the B2 cohort, PDC*lung01 exhibited a mild safety profile. Most treatment-emergent adverse events (TEAEs) were grades 1-2, with only one grade 4-related TEAE reported.
Only 2% of related TEAEs led to discontinuation, compared to 9.1% for pembrolizumab alone in the KEYNOTE-042 study.
Further data from the trial will become available at the end of 2025, once all patients have reached two years of follow-up. Based on these very encouraging findings, PDC*line Pharma is preparing a randomized phase IIb study in untreated stage IV NSCLC (and PD-L1 ≥50%) in combination with pembrolizumab, with initiation planned in 2026.
"We are thrilled by these promising results, which position PDC*lung01 as the first cancer vaccine of its kind tested in metastatic NSCLC with high PD-L1 expression. 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. Moreover, our off-the-shelf technology has significant potential for expansion into other clinical settings and indications. Our upcoming randomized Phase IIb trial is a critical step toward confirming clinical proof of concept and fostering collaborations with industrial partners to bring our innovative technology to market," said Eric Halioua, CEO of PDC*line Pharma.
About PDC*lung01:
PDC*lung01 is an off-the-shelf cancer vaccine composed of irradiated human Plasmacytoid Dendritic Cells (PDC*line) loaded with peptides derived from key tumor antigens (NY-ESO-1, MAGE-A3, MAGE-A4, Multi-MAGE-A, MUC1, Survivin, Melan-A). These professional antigen-presenting cells prime and boost cytotoxic CD8+ T-cells, making the vaccine synergistic with checkpoint inhibitors like pembrolizumab.