Table 4 Biomarkers that predict response to DDR-targeted therapies in combination with ICB
Factor | Agents | Incidence (%) | Validated in clinical trial? | Association with favorable clinical outcome | Predictive versus prognostic | Cancer type | Tissue type for biomarker assessment | Possible assay type for biomarker assessment |
|---|---|---|---|---|---|---|---|---|
Mutational signature 3 reflecting HRD, IS | Niraparib, pembrolizumab | 51% | I/II (NCT02657889) | Positive | Prognostic, predictive, or both | Ovarian cancer | Tumor tissue | Targeted gene panel sequencing |
Pre-existing CD8+ T-cell infiltrates | Durvalumab, olaparib | NR | II (NCT02484404) | Positive | Predictive | Relapsed SCLC | Tumor tissue | Immunohistochemistry |
MDSCs (≤ the median) | Durvalumab, olaparib | NR | I/II (NCT02484404) | Negative | Prognostic | MCRPC | Blood | Multiparametric flow cytometry |
CTC | Durvalumab, olaparib | NR | I/II (NCT02484404) | Positive | Prognostic | MCRPC | Blood | Multiparametric flow cytometry |
CD83 expression on CD141+ mDCs, > median percentage of Ki67 + PD-1+ cells among total CD8+/CD4+ T cells, > median percentage of Ki67+ HLA-DR CD8+ and CD4+ T cells | Durvalumab, olaparib | NR | I/II (NCT02484404) | Positive | Prognostic | mCRPC | Blood | Multiparametric flow cytometry |