TEST:

PD-L1 IHC 73-10 pharmDx

Efficacy of avelumab for high-risk TNBC did not significantly differ by PD-L1 in the ITT, or by TILs and RCB in Stratum B. However, these biomarkers help identifying subgroups of patients at poorer prognosis deriving the greatest magnitude of benefit from this treatment.

The prognostic value of PD-L1 expression in both IC and TC differs between antibody clones, with 73-10 and SP263 being more reliable for prognostic information than 22C3 in resected CRC.

"The 73-10 clone assay's sensitivity ranged from 78.3% to 100% (TPS ≥1%), 100% (TPS ≥50%), and 77.4% to 93.5% (IPS ≥1%), while its specificity was 97.9% to 100% (TPS ≥1%), 99.5% to 99.8% (TPS ≥50%), and 97.9% to 100% (IPS ≥1%). This exploratory evaluation of LBS 73-10 monoclonal antibody on a large set of breast, colorectal, and hepatocellular carcinomas showed the assay's technical performance is comparable to the FDA-approved companion/complementary diagnostics PD-L1 detection assays."

PD-L1 CDx assays are critical for patient selection for anti PD1/PD-L1 checkpoint inhibitor treatment. Recently, it was reported that post translational modifications on PD-L1 can affect antibody detection thereby resulting in false negative diagnosis in a PD-L1 CDx assay.Using whole slide digital image analysis, quantitative mass spectroscopy and immunohistochemistry, we have developed and validated a multimodality workflow to quantitatively characterize total and glycosylated PD-L1 levels in FFPE tumor resections.We have investigated the impact of PD-L1 glycosylation on the detection sensitivity for two different PD-L1 antibody clones (73-10 and SP263) that are used in CDx assays and demonstrate that these clones are not affected by this post-translational modification.

P3; Longer median OS and PFS were observed with avelumab vs platinum-based doublet chemotherapy in advanced NSCLC, but differences in OS and PFS were not statistically significant, and the trial did not meet its primary objective.

Our analysis revealed high OPA between 73-10 and 22C3 as well as between 73-10 and 28-8. Further, our results of PPA and NPA might indicate that the results of 73-10 could be translated to those of 22C3 or those of 28-8. It was also indicated that the results of 22C3 could be translated to those of 73-10.

This study demonstrates that the location and conformation of binding sites, recognized by antibodies employed in PD-L1 diagnostic assays differ significantly and exhibit differing degrees of robustness. These findings should reinforce the need for vigilance when performing clinical testing with different PD-L1 IHC assays, particularly in the control of cold ischemia and the selection of fixation and decalcification conditions.

This pilot study demonstrates that most LACs are PDL1 negative, indicating that corresponding immunotherapy would be ineffective in these patients. The results are further supported by the Leica PD-L1 clone used in the study, because this clone 73-10 was reported to be more sensitive compared with the Dako PD-L1 22C3 pharmDx clone.

This pilot study demonstrates that most LACs are PDL1 negative, indicating that corresponding immunotherapy would be ineffective in these patients. The results are further supported by the Leica PD-L1 clone used in the study, because this clone 73-10 was reported to be more sensitive compared with the Dako PD-L1 22C3 pharmDx clone.

PD-L1 expression is common in GEP-NENs and increases with malignancy. Therefore, especially in high-grade GEP-NENs, targeting the PD-1/PD-L1 axis could be a promising additional therapeutic strategy.

MPM is an aggressive tumour. BAP1 is the most common somatic mutation, and its loss of expression remains to be common regardless of tumour grade or PD-L1 status. In epithelioid MPMs, expression of PD-L1 seems to be associated with certain histologic features such as rhabdoid morphology, but not with tumour grade or BAP1 expression.

JAVELIN Lung 100 did not meet its primary objective of demonstrating superior OS or PFS by IRC with 1L avelumab (Q2W or QW) vs platinum-based doublet chemotherapy in patients with high-expression PD-L1+ tumors. The safety profile of avelumab was consistent with that observed in previous studies of avelumab monotherapy.

The positive rate on ICs and TCs of the 73-10 assay was higher than that of the SP 142 and E1L3N assays. Although substantial agreement on ICs and moderate agreement on TCs between the 73-10 and SP142 assays was noted in the present cohort, further studies are needed to clarify the PD-L1 expression status using various primary antibodies in a larger patient population. This would lead to the establishment of an effective evaluation method to assess the predictive value of anti-PD-L1 immunotherapy.

Positivity for PD-L1 expression by 73-10, as compared to 28-8, was associated with worse clinicopathological factors and prognosis for patients with RCC.

The SP142 assay showed distinct expression patterns between IC (granular, dot-like) and TC (membranous) while 73-10 and E1L3n showed membranous and/or cytoplasmic expression in both IC and TC. Most MpBC in our cohort were positive for PD-L1 indicating eligibility for anti-PD-L1/programmed death-1 immunotherapy.

CD155 may be a novel target for antitumor immunotherapy. The results of this study indicate that CD155 may expand the pool of candidates with triple-negative breast cancer who could benefit from antitumor immunotherapy.

Phase II study of avelumab + chemotherapy (docetaxel, cisplatin and 5-FU or mDCF) given every 2 weeks for 4 cycles before and after surgery...Main exclusion criteria: use of immunosuppressants, serious autoimmune disease, daily intake >10 mg prednisone... The combination of mDCF chemotherapy with Avelumab demonstrates a promising safety and activity profile . Ongoing laboratory investigations are underway to correlate our findings with tumor molecular features before exposure to treatment.

Although the JAVELIN Lung 200 primary analysis (reported previously) showed that avelumab did not significantly prolong OS vs docetaxel in patients with platinum-treated PD-L1+ NSCLC, post hoc analyses at 2 years of follow-up showed that 2-year OS rates were doubled with avelumab in subgroups with higher PD-L1 expression (≥50% and ≥80%).

A survey of PD-L1 staining in a wide range of pancreatic neoplasms shows enrichment of PD-L1 staining in IOPN. These findings were demonstrated using two different PD-L1 clones. These results suggest unique immunogenicity in IOPN compared to that of other pancreatic neoplasms, and that immunotherapy may have a role in the treatment of IOPN.

Our results indicated moderate association of PD-L1 expression between gastric biopsies and corresponding resected tumors. Results of PD-L1 assay with 73-10 are comparable to 22C3 pharmDx results.

P1 | "The 73-10 assay showed high sensitivity for PD-L1 staining, and staining was comparable between the ≥80% cutoff of the 73-10 assay and ≥50% cutoff of the 22C3 assay."