TEST:

VENTANA PD-L1 (SP142) Assay

PD-L1 expression may differ between biopsy specimens and surgically resected specimens in patients with advanced NSCLC, even in patients who have not received neoadjuvant therapy. Consequently, PD‑L1 status evaluated from biopsy specimens should be interpreted with caution in clinical practice. In addition, the selection of PD-L1 immunohistochemistry (IHC) detection methods may also affect the evaluation results.

Carboplatin plus nivolumab did not significantly improve PFS compared to carboplatin in patients overall; however, a trend toward improved outcomes was observed in PD-L1-positive mTNBC patients. High mutational burden, interferon-gamma signaling, early circulating tumor DNA reduction, low baseline serum thymidine kinase activity, and urea cycle dysregulation in the microbiome emerged as potential predictors of response to immune checkpoint inhibitors with platinum.

P2, N=110, Recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Apr 2026 --> Apr 2027

Our results suggest that cPD-L1 expression in most sUC occurs secondary to IL6-JAK-STAT3 and interferon α/γ signaling. This provides a biologic rationale for evaluating response to immunotherapy in this patient population.

P3, N=60, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Dec 2026 --> Dec 2025

Clone selection is critical in PD-L1 immunohistochemistry, and 28-8-based CPS appears to be a practical biomarker for guiding nivolumab treatment in this setting.

P1/2, N=104, Recruiting, Consorzio Oncotech | Not yet recruiting --> Recruiting

P1, N=24, Terminated, Imugene Limited | Active, not recruiting --> Terminated; Portfolio prioritization

P3, N=60, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Jun 2026 --> Dec 2026

The 22C3 and SP142 assays show analytical concordance for overall PD-L1 status but significant variability in IC scoring. Given the variability in PD-L1 expression across UC-s, precise characterization of both TC and IC staining per assay is crucial. These findings support incorporating UC-s subtype and assay-specific PD-L1 profiles into routine diagnostics to optimize immunotherapy decisions.

In this real-world study, PD-L1-positive prevalence was lower than in prospective trials assessing PD-L1 status centrally, lower in mTNBC than eTNBC, lower in smaller than larger tissue samples and lower by local than central assessment. These findings underline the importance of central PD-L1 testing on sufficiently large samples to ensure optimal selection for therapies targeting PD-(L)1 in mTNBC.

P2, N=81, Active, not recruiting, Institut Curie | Recruiting --> Active, not recruiting | N=130 --> 81