Dataset Information

The Applicability of the Results in the Asian Population of ORIENT-11 to a Western Population According to the ICH-E5 Framework.

ABSTRACT: Sintilimab combined with pemetrexed and platinum met the primary endpoint of improving progression-free survival (PFS) as a first-line therapy for nonsquamous non-small cell lung cancer (NSCLC) in the phase 3 trial ORIENT-11 (NCT03607539). As seen in similar trials, the addition of sintilimab, a PD-1 inhibitor, to chemotherapy improved the PFS without significantly worsening the toxicity, with improvements in response rate and duration of response. In contrast to previous trials, the ORIENT-11 trial was conducted completely in China. Both intrinsic and extrinsic factors are important to consider when reviewing foreign clinical trial data, as they may influence the efficacy and the safety outcomes. Here we discuss the applicability of ORIENT-11 clinical results to a Western population.

SUBMITTER: Liu SV

PROVIDER: S-EPMC9226396 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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The Applicability of the Results in the Asian Population of ORIENT-11 to a Western Population According to the ICH-E5 Framework.

Liu Stephen V SV Nagasaka Misako M Stefaniak Victoria V Gruver Kristi K Lin Yong Y Ferry David D Socinski Mark A MA Zhang Li L

Frontiers in oncology 20220610

Sintilimab combined with pemetrexed and platinum met the primary endpoint of improving progression-free survival (PFS) as a first-line therapy for nonsquamous non-small cell lung cancer (NSCLC) in the phase 3 trial ORIENT-11 (NCT03607539). As seen in similar trials, the addition of sintilimab, a PD-1 inhibitor, to chemotherapy improved the PFS without significantly worsening the toxicity, with improvements in response rate and duration of response. In contrast to previous trials, the ORIENT-11 t ...[more]

PMID: 35756655

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Project description:BackgroundMesenchymal stem/stromal cells (MSC) have immunomodulatory properties, studied in a wide range of diseases. Validated quality controls must confirm this activity in the context of clinical trials. This study presents a method's validation, assessing MSC's ability to inhibit lymphocyte proliferation, according to the ICH Q2 standard.MethodsMSC were co-cultured with CellTrace™ Violet-labeled Peripheral blood mononuclear cells (PBMC) coming from a bank of ten donors, at seven different ratios for 7 days. Cell trace violet PBMC bank was validated in parallel. Flow cytometry analysis was used to obtain the division percentage of T cells. The percentage of inhibition of lymphocyte proliferation by MSC, for each ratio X, was calculated using the formula: Ratio × percentage of inhibition = (control percentage of division-ratio × percentage of division)/control percentage of division. The inhibition percentage of lymphocyte proliferation function of co-culture ratios was represented in a line graph. The corresponding area under the curve was calculated, representing MSC's ability to inhibit lymphocyte proliferation.ResultsTwo cell trace violet PBMC banks were compared for bank validation. When compared using four different MSC samples coming each from a different donor, their area under the curve did not show any statistical differences and were correlated. Moreover, the stability of one cell trace violet PBMC bank was confirmed up to 509 days of storage. Analytical parameters were investigated for method validation. Analysis of repeatability and reproducibility respectively showed a standard deviation of 6.1% and 4.6%. The assay was robust regarding PBMC, as no statistical differences were found between inhibitory activities when testing three adjacent concentrations of PBMC. Still, attention is needed on MSC quantity as it can influence results. Linearity was evaluated: the percentage of inhibition of lymphocyte proliferation function of co-culture ratios was linear on the exploited range. Finally, the assay measurement range allowed to differentiate MSC presenting different inhibition activities.ConclusionThis quantification method displayed low analytical variability and no inter-bank variability of PBMC. However, MSC quantification should be checked before co-culture to reduce variability. Therefore, it could be used for the qualification of MSC batches' immunomodulatory activity.

Dataset Information

The Applicability of the Results in the Asian Population of ORIENT-11 to a Western Population According to the ICH-E5 Framework.

Publications

The Applicability of the Results in the Asian Population of ORIENT-11 to a Western Population According to the ICH-E5 Framework.

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