PD-L1 negative

nCIT establishes a new standard of care for resectable non-small cell lung cancer, offering improved pathological and survival outcomes while preserving surgical safety. Future research should focus on unresolved issues such as patient selection, biomarker integration and the role of adjuvant immunotherapy to refine personalized treatment strategies.

P1/2, N=420, Recruiting, BioNTech SE

Our findings suggest that PD-L1-negative cases represent a high-risk biological subset driven by alternative immune evasion mechanisms. Integrating TIL density with conventional pathological parameters provides a more robust prognostic framework, enabling personalized therapeutic strategies for this challenging malignancy.

Our observations suggest an association between PD-L1 expression on immune cells and immune-activated versus mesenchymal-dominant states, potentially occurring within macrophage-enriched stromal niches. These results provide insight into the biological mechanisms underlying disease progression and highlight tumor-associated macrophages as a potential therapeutic target to overcome immune resistance, particularly in PD-L1-negative MSS-CRC tumors.

PD-L1 expression is a useful biomarker for predicting postoperative recurrence in patients with EGFR-mutant LUAD, and the therapeutic effect of EGFR-TKIs is sufficient even in PD-L1-positive patients. These findings support the current treatment guidelines and highlight the need for further studies to explore the role of PD-L1 in postoperative management.

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

Three distinct PD-L1 expression patterns within tumor budding areas are associated with clinicopathologic features and immune cell infiltration profiles. PD-L1 expression patterns may warrant further investigation as potential biomarkers for immunotherapy response.

IO102-IO103 plus pembrolizumab prolonged progression-free survival compared with pembrolizumab alone in patients with advanced melanoma in the first-line setting; however, statistical significance was missed for the primary endpoint. The combination was well tolerated with no added significant systemic toxicity. These data show the potential benefit of this combination in untreated advanced melanoma.

P2, N=51, Active, not recruiting, The Methodist Hospital Research Institute | N=39 --> 51 | Trial completion date: Dec 2025 --> Dec 2028

P3, N=750, Recruiting, Amgen | Trial completion date: Jun 2031 --> Jun 2032 | Trial primary completion date: Jun 2026 --> Jun 2027

The standard first-line treatment for patients with driver mutation-negative non-small cell lung cancer (NSCLC) is chemotherapy and immunotherapy, including chemotherapy plus anti-programmed death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibody (C + PD-1/PD-L1) or anti-PD-1 antibody (nivolumab) and anti-cytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) (C + NI)...In the C + PD-1/PD-L1 group, platinum doublets were administered for up to four cycles, with pemetrexed maintenance permitted when the initial regimen included pemetrexed, whereas in the C + NI group, platinum doublets were limited to a maximum of two cycles with no maintenance chemotherapy...C + NI did not demonstrate superior effectiveness compared with C + PD-1/PD-L1 treatment across the PD-L1 TPS subgroups and was associated with increased toxicity, suggesting no clear clinical advantage of prioritizing C + NI in routine practice. C + NI should be reserved for selected cases in which the potential benefits outweigh the risks.

P1/2, N=132, Recruiting, Antengene Biologics Limited | Not yet recruiting --> Recruiting