The overall survival rate was 20

The overall survival rate was 20.2 months for patients with PD-L1 high-expressing tumors treated with atezolizumab compared to 13.1 months for patients treated with chemotherapy, and patients with PD-L1-positive tumors (tumor proportion score 1%) had an OS of 17.8 months in the atezolizumab-treated cohort compared to 14.1 months in the chemotherapy-treated (78). Fig. 1 FDA approvals of PD-1/PD-L1 mAbs. AR-42 (HDAC-42) As of December 2020, six anti-PD-1/PD-L1 mAbs have been approved with supplemental indications across 19 malignancy types and two tissue-agnostic conditions. Shown are the approvals for each cancer indication, for Keytruda (pembrolizumab), Opdivo (nivolumab), Libtayo (cemiplimab), Tecentriq (atezolizumab), Bavencio (avelumab), and Imfinzi (durvalumab). Multiple approvals for any cancer indication within the same 12 months are shown with only one symbol. The open symbols represent approvals without a biomarker (no BM). The full symbols represent approvals that incorporate a biomarker with an associated threshold for each indication (BM), which was measured using either a central laboratory test or complementary diagnostic that was not approved as a CDx for the drug. Symbols with a reddish outline symbolize approvals in which a companion diagnostic is usually indicated for biomarker measurement (BM + CDx). *: approval for MSI-H/dMMR colorectal malignancy. PM, pleural mesothelioma; TNBC, triple-negative breast malignancy; CSCC, cutaneous squamous cell carcinoma; TMB-H, tumor mutation burden high; CRC, colorectal malignancy; BCG-BC, Bacillus Calmette-Gurin bladder malignancy; EC, endometrial carcinoma; ESCC, esophageal squamous cell carcinoma; SCLC, small cell lung malignancy; RCC, renal cell carcinoma; MCC, Merkel cell carcinoma; HCC, hepatocellular carcinoma; PMBCL, main mediastinal large B cell lymphoma; CC, cervical malignancy; GC, gastric malignancy; MSI-H, microsatellite instability high; dMMR, mismatch repair-deficient; UC, urothelial AR-42 (HDAC-42) carcinoma; cHL, classical Hodgkins lymphoma; HNSCC, head and neck squamous cell carcinoma; NSCLC, non-small cell lung malignancy. Information on approvals and supplemental approvals was gathered from Drugs@FDA FDA-APPROVED ANTI-PD-1/PD-L1 THERAPIES The standard of care for several malignancy types currently includes treatment with monoclonal antibodies (mAbs) specific to PD-1 or PD-L1. PD-1 (CD279) is usually a co-inhibitory transmembrane protein that is expressed on antigen-stimulated T and B lymphocytes, natural killer (NK) cells, and myeloid suppressor dendritic cells (MDSCs). Following acknowledgement of antigens or activation from AR-42 (HDAC-42) cytokines, PD-1 is activated as a AR-42 (HDAC-42) mechanism to modulate the intensity of the immune response (7). The engagement of PD-1 with its cognate ligands PD-L1 (B7-H1) or PD-L2 (B7-DC), which are widely expressed on tumor cells, results in the inhibition of T cell activation or proliferation and subsequently T cell exhaustion (3, 7, 8). While ICIs have demonstrated improved clinical efficacy, only a small proportion of patients respond to single-agent treatment. PD-L1 protein expression was the primary immuno-oncology biomarker, with the expression on immune cells and tumor cells being evaluated and quantified using immunohistochemistry (IHC) assays. The argument on whether PD-L1 expression levels are predictive of a response has been assessed through prospective or retrospective analysis, resulting in many ICI approvals with biomarker-independent treatment indications (1, 3). There remains a lack of universal predictive biomarker for individual selection for ICI treatment. Anti-PD-1 mAbs Three anti-PD-1 antibodies have been approved by the FDA: pembrolizumab (Keytruda), nivolumab (Opdivo), and cemiplimab (Libtayo). Pembrolizumab (Keytruda) Pembrolizumab, a humanized IgG4 antibody against PD-1, was initially approved AR-42 (HDAC-42) by the FDA in September Rabbit Polyclonal to SP3/4 2014 following results from the KEYNOTE-001 clinical trial (“type”:”clinical-trial”,”attrs”:”text”:”NCT01295827″,”term_id”:”NCT01295827″NCT01295827), studying patients with unresectable or metastatic melanoma and patients with non-small cell lung malignancy?(NSCLC). These malignancy types were chosen as there were previously seen high levels of PD-L1 expression (9, 10). The approval was specified for the treatment of patients with unresectable or metastatic melanoma and disease progression after receiving ipilimumab.