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| Profile Name | CD274 over exp |
| Gene Variant Detail | |
| Relevant Treatment Approaches | PD-L1/PD-1 antibody |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| CD274 over exp | Advanced Solid Tumor | predicted - sensitive | PD-L1/PD-1 antibody | PF-06801591 | Phase I | Actionable | In a Phase I trial, treatment with PF-06801591 resulted in a greater overall objective response in patients with an advanced solid tumor and higher CD274 expression (n=10), including four partial responses and two patients with stable disease, compared to those patients with lower CD274 expression (n=20), which included one partial response and ten patients with stable disease (PMID: 31145415; NCT02573259). | 31145415 |
| CD274 over exp | lung non-small cell carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Clinical Study - Meta-analysis | Actionable | In a meta-analysis, treatment with immune checkpoint inhibitors including Tecentriq (atezolizumab), Opdivo (nivolumab), Yervoy (ipilimumab), and Keytruda (pembrolizumab) resulted in improved progression-free survival (HR=0.41, p<0.001) and overall survival (HR=0.62, p=0.006) in non-small cell lung cancer patients with high CD274 (PD-L1) expression compared to patients with low CD274 (PD-L1) expression (PMID: 31290993). | 31290993 |
| CD274 over exp | lung non-small cell carcinoma | sensitive | PD-L1/PD-1 antibody | Atezolizumab | Clinical Study - Meta-analysis | Actionable | In a meta-analysis, treatment with immune checkpoint inhibitors including Tecentriq (atezolizumab), Opdivo (nivolumab), Yervoy (ipilimumab), and Keytruda (pembrolizumab) resulted in improved progression-free survival (HR=0.41, p<0.001) and overall survival (HR=0.62, p=0.006) in non-small cell lung cancer patients with high CD274 (PD-L1) expression compared to patients with low CD274 (PD-L1) expression (PMID: 31290993). | 31290993 |
| CD274 over exp | lung non-small cell carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Nivolumab | Clinical Study - Meta-analysis | Actionable | In a meta-analysis, treatment with immune checkpoint inhibitors including Tecentriq (atezolizumab), Opdivo (nivolumab), Yervoy (ipilimumab), and Keytruda (pembrolizumab) resulted in improved progression-free survival (HR=0.41, p<0.001) and overall survival (HR=0.62, p=0.006) in non-small cell lung cancer patients with high CD274 (PD-L1) expression compared to patients with low CD274 (PD-L1) expression (PMID: 31290993). | 31290993 |
| CD274 over exp | lung non-small cell carcinoma | predicted - sensitive | Ipilimumab | Clinical Study - Meta-analysis | Actionable | In a meta-analysis, treatment with immune checkpoint inhibitors including Tecentriq (atezolizumab), Opdivo (nivolumab), Yervoy (ipilimumab), and Keytruda (pembrolizumab) resulted in improved progression-free survival (HR=0.41, p<0.001) and overall survival (HR=0.62, p=0.006) in non-small cell lung cancer patients with high CD274 (PD-L1) expression compared to patients with low CD274 (PD-L1) expression (PMID: 31290993). | 31290993 | |
| CD274 over exp | lung adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Atezolizumab | Guideline | Actionable | Tecentriq (atezolizumab) is included in guidelines as preferred first-line therapy for patients with advanced or metastatic lung adenocarcinoma with CD274 (PD-L1) expression of at least 50% and negative for actionable molecular biomarkers (NCCN.org). | detail... |
| CD274 over exp | lung large cell carcinoma | sensitive | PD-L1/PD-1 antibody | Atezolizumab | Guideline | Actionable | Tecentriq (atezolizumab) is included in guidelines as preferred first-line therapy for patients with advanced or metastatic large cell lung cancer with CD274 (PD-L1) expression of at least 50% and negative for actionable molecular biomarkers (NCCN.org). | detail... |
| CD274 over exp | lung squamous cell carcinoma | sensitive | PD-L1/PD-1 antibody | Atezolizumab | Guideline | Actionable | Tecentriq (atezolizumab) is in guidelines as preferred first-line therapy for patients with advanced or metastatic lung squamous cell carcinoma with CD274 (PD-L1) expression of 50% or more, and negative for actionable molecular biomarkers (NCCN.org). | detail... |
| CD274 over exp | lung non-small cell carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, non-small cell lung carcinoma patients with a CD274 (PD-L1) TPS of >=50% treated with Opdivo (nivolumab) achieved an overall response rate of 45.8% vs. 15.9% (p=0.002) and a median progression-free survival of 8.1 months vs. 2.2 months (HR=0.54; 95% CI: 0.33-0.90; p=0.02), and demonstrated an overall survival benefit (HR=0.44; 95% CI: 0.23-0.84; p=0.01) compared to patients with a TPS of < 50% (PMID: 32955570). | 32955570 |
| CD274 over exp | B-cell lymphoma | sensitive | CD19-PD-1/CD28-CAR T cells | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CD19-PD-1/CD28 CAR T cell treatment induced dose-dependent cytotoxicity against a B cell lymphoma cell line with CD274 overexpression in culture, and resulted in greater inhibition of tumor growth in a cell line xenograft model compared to treatment with anti-CD19 CAR T cells alone or combined with an anti-PD-1 antibody (PMID: 33028589). | 33028589 | |
| CD274 over exp | lung non-small cell carcinoma | sensitive | PD-L1/PD-1 antibody | Cemiplimab | Guideline | Actionable | Libtayo (cemiplimab) is included in guidelines as preferred first-line therapy for patients with advanced or metastatic non-small cell lung cancer, not otherwise specified, with CD274 (PD-L1) expression of at least 50% and negative for actionable molecular biomarkers; and as continued maintenance therapy (NCCN.org). | detail... |
| CD274 over exp | lung non-small cell carcinoma | sensitive | PD-L1/PD-1 antibody | Atezolizumab | Guideline | Actionable | Tecentriq (atezolizumab) is included in guidelines as preferred first-line therapy for patients with advanced or metastatic non-small cell lung cancer, not otherwise specified, with CD274 (PD-L1) expression of at least 50% and negative for actionable molecular biomarkers (NCCN.org). | detail... |
| CD274 over exp | gastroesophageal junction adenocarcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Clinical Study - Cohort | Actionable | In a combined analysis of three clinical trials, Keytruda (pembrolizumab) treatment resulted in favorable outcome in gastric or gastroesophageal junction cancer patients with CD274 (PD-L1) combined positive score (CPS) of 10 or higher, median overall survival, objective response rate, and duration of response were 8 mo, 17% (8/46), 21 mo in KEYNOTE-059, 10 mo, 25% (13/53), not reached in KEYNOTE-061, 17 mo, 25% (23/92), 19 mo in KEYNOTE-062 (PMID: 33446564; NCT02335411, NCT02370498, NCT02494583). | 33446564 |
| CD274 over exp | stomach cancer | predicted - sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Clinical Study - Cohort | Actionable | In a combined analysis of three clinical trials, Keytruda (pembrolizumab) treatment resulted in favorable outcome in gastric or gastroesophageal junction cancer patients with CD274 (PD-L1) combined positive score (CPS) of 10 or higher, median overall survival, objective response rate, and duration of response were 8 mo, 17% (8/46), 21 mo in KEYNOTE-059, 10 mo, 25% (13/53), not reached in KEYNOTE-061, 17 mo, 25% (23/92), 19 mo in KEYNOTE-062 (PMID: 33446564; NCT02335411, NCT02370498, NCT02494583). | 33446564 |
| CD274 over exp | lung non-small cell carcinoma | sensitive | PD-L1/PD-1 antibody | Cemiplimab | Phase III | Actionable | In a phase III trial (EMPOWER-Lung 1), Libtayo (cemiplimab) therapy improved overall survival (18.7 vs 11.7 mo, HR 0.17, p=0.0091), progression-free survival (10.4 vs 5.3 mo, HR 0.45, p=0.0231), and objective response rate (41.2% vs 8.8%) compared to chemotherapy in patients with advanced non-small cell lung cancer with CD274 (PD-L1) expression equals to or over 50% and with brain metastases at baseline (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 9085-9085; NCT03088540). | detail... |
| CD274 over exp | lung non-small cell carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Retifanlimab | Phase II | Actionable | In a Phase II trial (POD1UM-203), Zynyz (retifanlimab) treatment was well tolerated and demonstrated antitumor activity in non-small cell lung cancer patients with high CD274 (PD-L1) expression, resulting in an objective response rate of 30.4% (7/23) and a disease control rate of 65.2% (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 2571-2571; NCT03679767). | detail... |
| CD274 over exp | penis squamous cell carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Cemiplimab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic squamous cell carcinoma of the penis harboring CDKN2A R80* with high CD274 (PD-L1) expression (IHC>95%) previously treated with cisplatin-based chemotherapy and radiotherapy achieved a complete response to treatment with Libtayo (cemiplimab), and maintained the complete response six months after treatment cessation (PMID: 34267641). | 34267641 |
| CD274 over exp | lung non-small cell carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Niraparib + Pembrolizumab | Phase II | Actionable | In a Phase II trial, combination Zejula (niraparib) and Keytruda (pembrolizumab) resulted in an objective response rate (ORR) of 56.3% (9/16; 2 complete, 7 partial responses), 19.7-mo median duration of response (mDR), and 8.4-mo median progression-free survival (mPFS) in non-small cell lung cancer patients with a CD274 (PD-L1) TPS>=50%, and an ORR of 20% (4/20; 4 partial responses), 9.4-mo mDR, and 4.2-mo mPFS in patients with a CD274 (PD-L1) TPS=1-49% (PMID: 34478166; NCT03308942). | 34478166 |
| CD274 over exp | lung non-small cell carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Phase III | Actionable | In a Phase III trial (KEYNOTE-024), treatment with Keytruda (pembrolizumab) improved progression-free survival (10.3 vs 6.0 months, HR=0.50, p<0.001) and estimated 6-month overall survival rate (80.2% vs 72.4%, HR=0.60, p<0.001) compared to chemotherapy in untreated advanced non-small cell lung cancer patients with CD274 (PD-L1) expression on over 50% of tumor cells, and with no EGFR activating mutations or ALK rearrangement (PMID: 27718847; NCT02142738). | 27718847 |
| CD274 over exp | pleomorphic adenoma carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Pimivalimab | Case Reports/Case Series | Actionable | In a Phase I trial, Pimivalimab (JTX-4014) treatment led to a partial response that was ongoing for at least 386 days in a patient with CD274 (PD-L1)-positive (100% staining) carcinoma ex-pleomorphic adenoma (PMID: 32989552; NCT03790488). | 32989552 |
| CD274 over exp | lung sarcomatoid carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Anlotinib + Cisplatin + Nab-paclitaxel + Sintilimab | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Anlotinib (AL-3818) and Sintilimab (IBI308) plus Platinol (cisplatin) and Abraxane (nab-paclitaxel) resulted in a partial response in a metastatic pulmonary sarcomatoid carcinoma patient with high CD274 (PD-L1) expression (IHC=70%), and the patient remained on Anlotinib (AL-3818) and Sintilimab (IBI308) maintenance therapy with sustained disease control for more than 1 year (PMID: 36267791). | 36267791 |
| CD274 over exp | breast cancer | sensitive | INCB086550 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, INCB086550 decreased CD274 (PD-L1) surface expression and tumor growth in a cell line xenograft model of breast cancer with high CD274 (PD-L1) expression (PMID: 35254416). | 35254416 | |
| CD274 over exp | colorectal cancer | sensitive | INCB086550 | Preclinical | Actionable | In a preclinical study, INCB086550 decreased CD274 (PD-L1) cell surface expression and inhibited tumor growth in a mouse model of colorectal cancer with CD274 (PD-L1) overexpression (PMID: 35254416). | 35254416 | |
| CD274 over exp | chondrosarcoma | predicted - sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Case Reports/Case Series | Actionable | In a clinical case study, Keytruda (pembrolizumab) treatment resulted in a complete response lasting 24 months in a patient with CD274 (PD-L1)-positive (95%) metastatic dedifferentiated chondrosarcoma also harboring NRAS G13R (PMID: 36465334). | 36465334 |
| CD274 over exp | lung non-small cell carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Cetrelimab | Phase Ib/II | Actionable | In a Phase I/II trial, Cetrelimab (JNJ-63723283) treatment demonstrated safety and resulted in an overall response rate (ORR) of 18.6% (38/204), clinical benefit rate (CBR) of 31.3% (64/204), median progression-free survival (mPFS) of 2.8 mo, and median overall survival (mOS) of 17.8 mo in patients with advanced solid tumors, with an ORR of 52.6% (10/19, all partial responses) and CBR of 73.7% (14/50) in non-small cell lung cancer patients with high CD274 (PD-L1) expression (PMID: 35298698; NCT02908906). | 35298698 |
| CD274 over exp | lung adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Cemiplimab | Guideline | Actionable | Libtayo (cemiplimab) is included in guidelines as preferred first-line therapy for patients with advanced or metastatic lung adenocarcinoma with CD274 (PD-L1) expression of at least 50% and negative for actionable molecular biomarkers; and as continued maintenance therapy (NCCN.org). | detail... |
| CD274 over exp | lung large cell carcinoma | sensitive | PD-L1/PD-1 antibody | Cemiplimab | Guideline | Actionable | Libtayo (cemiplimab) is included in guidelines as preferred first-line therapy for patients with advanced or metastatic lung large cell carcinoma with CD274 (PD-L1) expression of at least 50% and negative for actionable molecular biomarkers; and as continued maintenance therapy (NCCN.org). | detail... |
| CD274 over exp | lung squamous cell carcinoma | sensitive | PD-L1/PD-1 antibody | Cemiplimab | Guideline | Actionable | Libtayo (cemiplimab) is included in guidelines as preferred first-line therapy for patients with advanced or metastatic lung squamous cell carcinoma with CD274 (PD-L1) expression of at least 50% and negative for actionable molecular biomarkers; and as continued maintenance therapy (NCCN.org). | detail... |
| CD274 over exp | lung non-small cell carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | IO102-IO103 + Pembrolizumab | Phase II | Actionable | In a Phase II trial, treatment with the combination of IO102-IO103 and Keytruda (pembrolizumab) demonstrated safety and resulted in a partial response in 53.3% (8/15, 4 confirmed partial responses) and 5 with stable disease in non-small cell lung cancer patients with CD274 (PD-L1) expression (tumor proportion score >/=50%) (Ann Oncol (2023) 34 (suppl_2): S630; NCT05077709). | detail... |
| CD274 over exp | lung non-small cell carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Necitumumab + Pembrolizumab | Phase II | Actionable | In a Phase II trial, first-line treatment with Keytruda (pembrolizumab) plus Portrazza (necitumumab) resulted in an objective response rate of 76.0%, median progression-free survival of 15.7 months, and median overall survival that was not reached in patients with advanced non-small cell lung cancer with high CD274 (PD-L1) expression (>=50%) (n=50) (Cancer Res (2024) 84 (7_Supplement): CT032). | detail... |
| CD274 over exp | lung non-small cell carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | PDC*lung01 + Pembrolizumab | Phase Ib/II | Actionable | In a Phase I/II trial, treatment with the combination of PDC*lung01 and Keytruda (pembrolizumab) demonstrated safety in non-small cell lung cancer patients with CD274 (PD-L1) expression (>=50%) and resulted in an objective response rate of 63.2% (12/19, all partial responses), a disease control rate of 94.7%, a median progression-free survival of 10.9 months, and a median duration of response of 9.49 months (Cancer Res (2024) 84 (7_Supplement): CT021; NCT03970746). | detail... |
| CD274 over exp | head and neck squamous cell carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Eftilagimod alpha + Pembrolizumab | Phase II | Actionable | In a Phase II trial, Eftilagimod alpha (IMP321) and Keytruda (pembrolizumab) combination therapy resulted in an objective response rate (ORR) of 29.7% (11/37) and disease control rate (DCR) of 37.8% in patients with recurrent or metastatic head and neck squamous cell carcinoma, with an ORR of 60% (9/15), median progression-free survival of 13.6 months, and a median overall survival of 15.5 months in patients with high CD274 expression (PD-L1; CPS>/=20) (PMID: 38995265; NCT03625323). | 38995265 |
| CD274 over exp | lung non-small cell carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | PF-06801591 | Phase Ib/II | Actionable | In Phase Ib/II trial, PF-06801591 (sasanlimab) therapy was well tolerated in patients with locally advanced or metastatic non-small cell lung cancer and resulted in an objective response rate (ORR) of 16.4% (11/67, 11 partial responses), disease control rate of 56.7% (38/67), median progression-free survival of 3.7 months, and median overall survival of 14.7 months, with an ORR of 36.4% (4/11) in patients with high CD274 (PD-L1) expression (>/=50%) (PMID: 37385154; NCT02573259). | 37385154 |