News - PD-L1 amplification

A Phase Ⅰ/II Clinical Study of SYS6010 in combination with Enlonstobart ± chemotherapy in patients with locally advanced or metastatic NSCLC and other advanced solid tumor (ChiCTR2400089402)

P1/2, N=540, Not yet recruiting, Shanghai East Hospital; CSPC Megalith Biopharmaceutical Co., Ltd.

5 days ago

New P1/2 trial • Combination therapy • Metastases

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)

PD-L1 expression • EGFR mutation • ALK mutation • PD-L1 amplification

PD-L1 IHC 22C3 pharmDx

cisplatin • carboplatin • Enshuxing (enlonstobart)

16d

Vogt-Koyanagi-Harada-Like Uveitis Secondary to Pembrolizumab in Metastatic Gastric Cancer: A Case Report and Review of the Literature. (PubMed, Case Rep Oncol)

She continues on trastuzumab maintenance, and most recent imaging shows no evidence of disease. Oncologists should be aware of VKH-like disease as a possible immune-related adverse event and seek urgent ophthalmologic consultation when such symptoms arise.

16 days ago

Review • Journal • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)

HER-2 amplification • PD-L1 amplification

Keytruda (pembrolizumab) • Herceptin (trastuzumab) • 5-fluorouracil • leucovorin calcium

HER2 amplification and PD-L1 expression in invasive stratified mucin-producing carcinoma of the cervix: a clinicopathological analysis of eighteen cases (PubMed, Zhonghua Bing Li Xue Za Zhi)

PD-L1 is positive in most of the ISMC cases, while HER2 is amplified or lowly expressed in a small portion of them. Thus, it is possible to treat ISMC patients with therapies targeting PD-L1 and therapy targeting HER2.

1 month ago

Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)

PD-L1 expression • HER-2 amplification • HER-2 expression • PD-L1 amplification • HER-2 amplification + PD-L1 expression • PD-L1 expression + HER-2 overexpression

Molecular pathogenesis of adult T-cell leukemia/lymphoma (PubMed, Rinsho Ketsueki)

Here we summarize the current understanding of the molecular pathogenesis of ATLL, focusing on recent progress made by genetic, epigenetic, and single-cell analyses. These findings not only provide a deeper understanding of the molecular pathobiology of ATLL, but also have significant implications for diagnostic and therapeutic strategies.

1 month ago

Review • Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • IRF4 (Interferon regulatory factor 4) • PRKCB (Protein Kinase C Beta)

CDKN2A deletion • PD-L1 amplification • IRF4 mutation • PD-L1 mutation

2ms

Dendritic Cell-Targeted Nanoparticles Enhance T Cell Activation and Antitumor Immune Responses by Boosting Antigen Presentation and Blocking PD-L1 Pathways. (PubMed, ACS Appl Mater Interfaces)

MSNP-MaN-PDL1bp/CLT treatment upregulated the levels of effector molecules such as granzyme B and proinflammatory cytokines (IFNγ and INFα) in the tumor tissue, indicating antitumoral T cell responses. This strategy of utilizing nanoparticles to trigger DC activation while promoting T cell stimulation can be used to amplify the antitumor T cell responses and represents a promising alternative to anti-PD-L1 immunotherapy.

2 months ago

Journal

PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • GZMB (Granzyme B) • MRC1 (Mannose Receptor C-Type 1) • CD80 (CD80 Molecule)

PD-L1 expression • PD-L1 amplification • PD-1 positive

2ms

MET and concomitant mutations in pulmonary adenocarcinomas (ECP 2024)

Oncogenic activation of genes-drivers are responsible for resistance mechanisms either understood has resistance to METtargeted therapies and as primary resistance. Recently it has been reported that PI3K pathway alteration is common in concomitancy with METex14 and believed that confers primary resistance to MET TKI. Early identification of alterations in MET kinase domain at diagnosis, is crucial for understanding progression and resistance mechanism, to develop novel therapies or to design treatment strategies in order to improve patient outcomes.

2 months ago

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • SMO (Smoothened Frizzled Class Receptor)

TP53 mutation • KRAS mutation • EGFR mutation • HER-2 amplification • PIK3CA mutation • HER-2 mutation • PTEN mutation • MET exon 14 mutation • ALK mutation • MET mutation • PD-L1 amplification • SMO mutation • PIK3CA mutation + PTEN mutation

Oncomine Precision Assay

6ms

RICTOR amplification is associated with Rictor membrane staining and does not correlate with PD-L1 expression in lung squamous cell carcinoma. (PubMed, Pathol Oncol Res)

In conclusion, the correlation between RICTOR amplification and Rictor membrane staining suggests that the latter can potentially be used as a surrogate marker to identify lung SCC cases with RICTOR amplification. Since a significant proportion of PD-L1 negative SCC cases harbor RICTOR amplification, analyzing PD-L1 negative tumors by RICTOR FISH or Rictor IHC can help select patients who may benefit from mTORC2 inhibitor therapy.

6 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2)

PD-L1 expression • PD-L1 negative • PD-L1 amplification • RICTOR amplification • mTOR amplification

8ms

Primary pulmonary histiocytic sarcoma with high PD-L1 expression benefited from immunotherapy: A case report and bioinformatic analysis. (PubMed, Clin Respir J)

Here, we report a 45-year-old man who was diagnosed with primary pulmonary histiocytic sarcoma with systemic metastases, with partial remission (PR) treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, but it relapsed soon after therapy above. Following that, we found that the genetic alteration of PD-L1 was associated with poor prognosis in sarcoma patients in terms of overall survival (OS) (p = 1.51 × 10-4 ), progress-free survival (PFS) (p = 4.90 × 10-2 ) and disease-specific survival (DSS) (p = 4.90 × 10-2 ). To our knowledge, this may be the first reported case with high PD-L1 expression in primary pulmonary histiocytic sarcoma who may benefit from immunotherapy such as nivolumab and pembrolizumab significantly and safely.

8 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1)

PD-L1 expression • PD-L1 overexpression • PD-L1 amplification

Keytruda (pembrolizumab) • Opdivo (nivolumab) • doxorubicin hydrochloride • cyclophosphamide • vincristine • prednisone

9ms

GC 2nd Line Durvalumab(MEDI4736)/Tremelimumab Plus Paclitaxel Study (clinicaltrials.gov)

P1/2, N=58, Completed, Asan Medical Center | Active, not recruiting --> Completed

9 months ago

Trial completion

PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • POLD1 (DNA Polymerase Delta 1) • MSH3 (MutS Homolog 3) • PMS1 (PMS1 protein homolog 1) • POLD2 (DNA Polymerase Delta 2)

MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PD-L1 amplification • POLD1 mutation • MSH3 mutation • PMS2 mutation • MLH3 mutation • PMS1 mutation • POLD2 mutation

Imfinzi (durvalumab) • paclitaxel • Imjudo (tremelimumab)

9ms

Unraveling the Significance of MET Focal Amplification in Lung Cancer: Integrative NGS, FISH, and IHC Investigation. (PubMed, Mod Pathol)

Notably, a strong correlation was observed between focal amplification and PD-L1 expression, indicating potential therapeutic implications with combined MET inhibitor and immunotherapy for patients with both alterations. Our findings provide insights into the molecular complexity and clinical relevance of METamp in lung cancer, highlighting the role of MET focal amplification as an oncogenic driver and its feasibility as a primary biomarker to further investigate the clinical activity of MET inhibitors in future studies.

9 months ago

Journal • Next-generation sequencing • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase)

PD-L1 expression • MET amplification • MET overexpression • MET expression • PD-L1 amplification

9ms

Oridonin inhibits bladder cancer survival and immune escape by covalently targeting HK1. (PubMed, Phytomedicine)

This research strongly suggests that oridonin serves as a covalent inhibitor of HK1. Moreover, it indicates that functional cysteine residue of HK1 could operate as viable targets for selective inhibition. Consequently, oridonin exhibits substantial potential for the evolution of anti-cancer agents targeting the potential therapeutic target HK1 via metabolism immunomodulation.

9 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

CD8 (cluster of differentiation 8)

PD-L1 expression • PD-L1 amplification

9ms

Molecular and Treatment Characteristics of SMARCB1 or SMARCA4-Deficient Undifferentiated Tumor: Retrospective Case Series. (PubMed, Cancer Res Treat)

However, one having CD274 (PD-L1) amplification showed the response to immune checkpoint inhibitor and a good prognosis. We believed that this report could provide promising information for determining the optimal treatment option.

9 months ago

Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1)

PD-L1 amplification

10ms

MoST-TAP: Tiragolumab and Atezolizumab in Advanced Pan-cancer Patients (clinicaltrials.gov)

P2, N=96, Recruiting, Omico | Not yet recruiting --> Recruiting

10 months ago

Enrollment open • Pan tumor • Metastases

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)

PD-L1 expression • PD-L1 amplification

Tecentriq (atezolizumab) • Pegasys (pegylated interferon α -2a) • tiragolumab (RG6058)

11ms

SWOG S1609: Nivolumab and Ipilimumab in Treating Patients With Rare Tumors (clinicaltrials.gov)

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> May 2026 | Trial primary completion date: Oct 2024 --> May 2026

11 months ago

Trial completion date • Trial primary completion date

CD4 (CD4 Molecule)

PD-L1 overexpression • PD-L1 amplification

Opdivo (nivolumab) • Yervoy (ipilimumab) • ABP 206 (nivolumab biosimilar)

12ms

The genomic and immune landscapes of gastric cancer and their correlations with HER2 amplification and PD-L1 expression. (PubMed, Cancer Med)

The combination of HER2 amplification and PD-L1 expression in Chinese patients with GC could stratify the total populations into several subgroups with distinctive genomic and immune landscapes, which should be considered when making personalized treatment decisions.

12 months ago

Journal • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • KMT2D (Lysine Methyltransferase 2D) • CDH1 (Cadherin 1)

PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • HER-2 expression • ARID1A mutation • MYC amplification • PD-L1 amplification • HER-2 amplification + PD-L1 expression • CCNE1 mutation

12ms

High Prevalence of MYD88 and CD79B Mutations and PD-L1 Alterations in Bone Marrow Large B Cell Lymphoma Associated with Hemophagocytic Lymphohistiocytosis (ASH 2023)

To the best of our knowledge, this is the first study exploring the molecular genetics of bone marrow large B cell lymphoma with HLH. Our study suggesting bone marrow large B cell lymphoma with HLH showed frequent MYD88/CD79B and PD-L1 alterations. Our study provided clues for the pathogenesis of bone marrow large B cell lymphoma with HLH and identified potential druggable targets for future clinical trials.

12 months ago

PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • IGH (Immunoglobulin Heavy Locus) • TET2 (Tet Methylcytosine Dioxygenase 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CD79B (CD79b Molecule) • CD5 (CD5 Molecule) • PIM1 (Pim-1 Proto-Oncogene) • IRF4 (Interferon regulatory factor 4)

CD79B mutation • PD-L1 amplification • CD79B mutation • BCL6 translocation

12ms

Anti-tumor effect of PD-L1-targeting antagonistic aptamer-ASO delivery system with dual inhibitory function in immunotherapy. (PubMed, Cell Chem Biol)

This chimera not only blocks PD-L1/PD-1 but also achieves targeted delivery of the conjugated ASO to reduce both surface PD-L1 and total PD-L1 expression. Compared with the single blockade, this chimera with the dual inhibitory function synergistically inhibits PD-L1 to amplify immunotherapeutic efficacy, providing a promising synergistic strategy for immunotherapy.

12 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1)

PD-L1 expression • PD-L1 amplification

1year

Chromosome 9p Duplication Promotes T-Cell Exhaustion and Enhances Stem Cell Clonogenic Potential in JAK2-Mutant Myeloproliferative Neoplasms (ASH 2023)

In conclusion, our comprehensive characterization of the molecular interplay between JAK2V617F and chromosome 9 alterations, along with their immunological implications due to PD-L1 hyperactivation, fills a critical knowledge gap and provides valuable insights into the disease progression of 9p-MPNs. Further analysis is ongoing to explore the associations between 9p duplication and hematological parameters in 9p-MPN patients for a better understanding of the clinical implications of this genetic abnormality in MPNs.

1 year ago

PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • JAK2 (Janus kinase 2) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD34 (CD34 molecule) • CD14 (CD14 Molecule) • B3GAT1 (Beta-1,3-Glucuronyltransferase 1)

PD-L1 expression • PD-L1 amplification • JAK2 V617F • JAK2 mutation • JAK2 amplification

1year

Macrophages Play a Key Role in Controlling Tumor Growth and Response to Immunotherapy in Primary Central Nervous System Lymphoma (ASH 2023)

Blocking PD1 exhibits superior efficacy when macrophages are present, indicating T cells are not the only player in this tumoral scenario. As a result, our study suggests that a promising approach for treating primary CNS lymphomas would involve targeting both T cells and macrophages.

1 year ago

PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1)

PD-L1 amplification

1year

SWOG S1609: Nivolumab and Ipilimumab in Treating Patients With Rare Tumors (clinicaltrials.gov)

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024

1 year ago

Trial completion date • Trial primary completion date

CD4 (CD4 Molecule)

PD-L1 overexpression • PD-L1 amplification

Opdivo (nivolumab) • Yervoy (ipilimumab) • ABP 206 (nivolumab biosimilar)

1year

Concurrent predictors of an immune responsive tumor microenvironment within tumor mutational burden-high breast cancer. (PubMed, Front Oncol)

Along with MSI-H and PD-L1+, several biomarkers, including B2M mutation and CD274 amplification, may help predict ICI benefit amongst TMB-H tumors. Co-occurring biomarkers within TMB-H breast cancer warrant evaluation in larger cohorts for response or resistance to ICI to develop composite predictive biomarkers in MBC.

1 year ago

Journal • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • B2M (Beta-2-microglobulin) • CDH1 (Cadherin 1)

PD-L1 expression • TMB-H • MSI-H/dMMR • HER-2 negative • HER-2 mutation • TMB-L • PD-L1 amplification • B2M mutation • CDH1 mutation

VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™

1year

MoST-TAP: Tiragolumab and Atezolizumab in Advanced Pan-cancer Patients (clinicaltrials.gov)

P2, N=96, Not yet recruiting, Omico

1 year ago

New P2 trial • Pan tumor • Metastases

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)

PD-L1 expression • PD-L1 amplification

Tecentriq (atezolizumab) • Pegasys (pegylated interferon α -2a) • tiragolumab (RG6058)

over1year

Donor T cell STAT3 deficiency enables tissue PD-L1-dependent prevention of graft-versus-host disease while preserving graft-versus-leukemia activity. (PubMed, J Clin Invest)

In lymphoid tissues, the lack of host-tissue PD-L1 interaction with PD-1 reduced the inhibition of the GSH/Myc pathway despite reduced GSH production caused by STAT3 deficiency and allowed donor T cell functions that mediate GVL activity. Therefore, STAT3 deficiency in donor T cells augments PD-1 signaling-mediated inhibition of GSH/Myc pathways and augments dysfunction of T cells in GVHD target tissues while sparing T cells in lymphoid tissues, leading to prevention of GVHD while preserving GVL effects.

over 1 year ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • STAT3 (Signal Transducer And Activator Of Transcription 3)

PD-L1 amplification

over1year

Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)

P2, N=240, Recruiting, German Cancer Research Center | Not yet recruiting --> Recruiting

over 1 year ago

Enrollment open

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)

HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PALB2 mutation • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation

Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Itovebi (inavolisib) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)

over1year

Metabolic Intervention Liposome Boosted Lung Cancer Radio-Immunotherapy via Hypoxia Amelioration and PD-L1 Restraint. (PubMed, Adv Sci (Weinh))

Then, TPP-LND is wrapped with liposomes to form TPP-LND@Lip nanoparticles. By doing this, TPP-LND@Lip nanoparticles can sensitize RT by reversing the hypoxic microenvironment of tumors to generate more DNA damage and reducing the expression of PD-L1 via enhancing the adenosine 5'-monophosphate-activated protein kinase activation. As expected, these well-designed economical TPP-LND@Lip nanoparticles are more effective than conventional anti-PD-L1 antibodies to some extent.

over 1 year ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 expression • PD-L1 amplification

over1year

New Insights Into the Pathogenesis of T-Cell Lymphoma and How This May Guide Treatment (SOHO 2023)

TFHLs, which frequently carry mutations of TET2, DNMT3A, RHOA and IDH2, rarely seen in combination in other PTCL, have a higher response rate to hypomethylating agents such as 5-azacytidine and histone deacetylase inhibitors such as romidepsin. Tumors harboring SVs or amplification of CD274 may show greater sensitivity to immune checkpoint inhibitors. Four tumor microenvironment subgroups defined by expression profiling alone, may represent immunotherapy biomarkers.

over 1 year ago

PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • TET2 (Tet Methylcytosine Dioxygenase 2) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • JAK1 (Janus Kinase 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CD4 (CD4 Molecule) • JAK3 (Janus Kinase 3) • RHOA (Ras homolog family member A) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • TBX21 (T-Box Transcription Factor 21) • TYK2 (Tyrosine Kinase 2) • DUSP22 (Dual Specificity Phosphatase 22) • GATA3 (GATA binding protein 3) • USP22 (Ubiquitin Specific Peptidase 22)

PD-L1 expression • TP53 mutation • ALK positive • DNMT3A mutation • ALK fusion • NOTCH1 mutation • CDKN2A deletion • TET2 mutation • CDKN2A mutation • RB1 deletion • PD-L1 amplification • ALK negative • STAT3 mutation

azacitidine • Istodax (romidepsin)

over1year

Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)

P2, N=240, Not yet recruiting, German Cancer Research Center | Trial completion date: Dec 2029 --> Dec 2030 | Trial primary completion date: Apr 2029 --> Mar 2030

over 1 year ago

Trial completion date • Trial primary completion date

over1year

IGH::CD274 (PD-L1) rearrangement in diffuse large B cell lymphoma and its therapeutic implication. (PubMed, EJHaem)

DLBCL with PD-L1 overexpression is often resistant to R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisolone). Our patients responded to a combination of R-CHOP and a PD-1 inhibitor.

over 1 year ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1)

PD-L1 overexpression • PD-L1 amplification

Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine

over1year

Tantalum-Zirconium Co-Doped Metal-Organic Frameworks Sequentially Sensitize Radio-Radiodynamic-Immunotherapy for Metastatic Osteosarcoma. (PubMed, Adv Sci (Weinh))

Furthermore, a combination of TZM, X-ray, and anti-PD-L1 treatments amplify antitumor immunotherapy and efficiently arrest osteosarcoma growth and metastasis. These results indicate that TZM is a promising radiosensitizer for the synergistic RT and immunotherapy of metastatic osteosarcoma.

over 1 year ago

Journal • PD(L)-1 Biomarker • IO biomarker • Metastases

PD-1 (Programmed cell death 1) • CGAS (Cyclic GMP-AMP Synthase)

PD-L1 expression • PD-L1 amplification

over1year

DART: Nivolumab and Ipilimumab in Treating Patients With Rare Tumors (clinicaltrials.gov)

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

over 1 year ago

Enrollment closed

CD4 (CD4 Molecule)

PD-L1 overexpression • PD-L1 amplification

Opdivo (nivolumab) • Yervoy (ipilimumab)

over1year

Non-autonomous enhancement of gPDL1 CAR-T annihilates TNBC development (AACR 2023)

Despite the excellent anti-cancer activity, the atezolizumab-based chimeric antigen receptor (CAR) T cells showed a robust off-target effect. Overall, gPD-L1 CAR-T exhibits excellent anti-tumor activity against TNBCs, and it could be a promising immunotherapy tool to treat TNBCs in clinic. Furthermore, targeting glycosylation moiety on the tumor antigen is a novel approach to lessen CAR-T toxicity in patients.

over 1 year ago

PD(L)-1 Biomarker • IO biomarker

IFNG (Interferon, gamma)

PD-L1 expression • PD-L1 amplification

Tecentriq (atezolizumab) • gPD-L1 CAR-T

over1year

Characterisation of tumor microenvironment and prevalence of CD274/PD-L1 genetic alterations difference in colorectal Cancer. (PubMed, BMC Cancer)

The prevalence of PD-L1 genetic alterations was relatively low in CRC, but the aberrations usually correlate with aggressive nature. The correlation between PD-L1 genetic alterations and tumor immune features was only observed in dMMR CRC.

over 1 year ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CD68 (CD68 Molecule)

PD-L1 expression • MSI-H/dMMR • PD-L1 amplification

over1year

Tumor Microenvironment and Its Clinicopathologic and Prognostic Association in Cutaneous and Noncutaneous Angiosarcomas. (PubMed, Am J Clin Pathol)

Our HTG analyses confirmed a high degree of tumor and microenvironment heterogeneity. Cutaneous ASs, ASs without MYC amplification, and ASs located in the head and neck area seem to be the most immunogenic subtypes in our series.

over 1 year ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1)

PD-L1 expression • PD-L1 overexpression • MYC amplification • CD8 expression • PD-L1 amplification

HTG EdgeSeq Precision Immuno-Oncology Panel

over1year

PD-L1 gene amplification and focality: relationship with protein expression. (PubMed, J Immunother Cancer)

In conclusion, PD-L1 expression measured by IHC is influenced by PD-L1 amplification level and focality. Further correlation between amplification, focality, protein expression and therapeutic outcome for PD-L1 and other targetable genes warrants exploration.

over 1 year ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1)

PD-L1 expression • PD-L1 overexpression • PD-L1 amplification

PD-L1 IHC 22C3 pharmDx

over1year

Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)

P2, N=240, Not yet recruiting, German Cancer Research Center | Initiation date: Dec 2022 --> May 2023

over 1 year ago

Trial initiation date

HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation

almost2years

Diagnostic Accuracy of Slow-Capillary Endobronchial Ultrasound Needle Aspiration in Determining PD-L1 Expression in Non-Small Cell Lung Cancer. (PubMed, Adv Respir Med)

These retrospective study shows that slow-pull capillary aspiration carries an excellent diagnostic accuracy, almost equal to that one reported in literature, supporting its use in EBUS-TBNA for PD-L1 testing in NSCLC.

almost 2 years ago

Journal • Endobronchial ultrasound • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1)

PD-L1 expression • PD-L1 amplification

almost2years

Clinical and molecular features of ATM and BRCA2 mutations in metastatic prostate cancer. (ASCO-GU 2023)

ATM or BRCA2 mutations also predicted worse response to the AR-targeted abiraterone/enzalutamide therapies (HR 0.4, 0.3; CI 0.244-1.003, 0.172 – 0.6; P = 0.047, p < 0.001). We found that somatic ATM and BRCA2 mutations associated with differential OS outcomes, which may help tailor treatment decisions. At the molecular level, ATM- and BRCA2-mutated tumors exhibited differences in the landscape of co-occurring genomic and transcriptional features. These features unique to ATM or BRCA2 mutations can inform rationale for divergent treatment strategies and should be investigated.

almost 2 years ago

Clinical • Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker • IO biomarker • Metastases

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • RB1 (RB Transcriptional Corepressor 1) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • ALDH1A3 (Aldehyde Dehydrogenase 1 Family Member A3) • HES4 (Hes Family BHLH Transcription Factor 4)

TP53 mutation • BRCA2 mutation • TMB-H • ATM mutation • PD-L1 amplification • BRCA2 expression

MI Tumor Seek™

Xtandi (enzalutamide capsule) • abiraterone acetate

almost2years

GC 2nd Line Durvalumab(MEDI4736)/Tremelimumab Plus Paclitaxel Study (clinicaltrials.gov)

P1/2, N=58, Active, not recruiting, Asan Medical Center | Unknown status --> Active, not recruiting | Trial completion date: Jun 2021 --> Jun 2023 | Trial primary completion date: Jun 2021 --> Jun 2023

almost 2 years ago

Enrollment closed • Trial completion date • Trial primary completion date • Metastases

MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PD-L1 amplification • POLD1 mutation • MSH3 mutation • PMS2 mutation • MLH3 mutation • PMS1 mutation • POLD2 mutation

Imfinzi (durvalumab) • paclitaxel • Imjudo (tremelimumab)

almost2years

Prevalence of Predictive Biomarkers Detected by Comprehensive Genomic Profiling in Pineal Parenchymal Tumors (USCAP 2023)

Clinically advanced PPTs appear to be genomically stable neoplasms with low GA per tumor, extremely limited targeted therapy options with the exception of the MTOR pathway and limited immunotherapy options given the absence of MSI-high status and low TMB.

almost 2 years ago

Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker

PD-L1 expression • MSI-H/dMMR • TMB-L • PD-L1 amplification

PD-L1 IHC 22C3 pharmDx

almost2years

Molecular and Clinicopathologic Characterization of HER2-Overexpressed and HER2/neu-Amplified Squamous Cell Carcinoma of the Cervix (USCAP 2023)

HER2 immunohistochemistry is a reliable predictive marker of HER2 gene amplification in squamous cell carcinoma of the cervix. HER2 overexpression and/or HER2 amplification are associated with poor prognostic factors, such as increased tumor grade, size, and depth of invasion, as well as nodal metastasis.

almost 2 years ago

Clinical

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • JAK2 (Janus kinase 2) • BIRC3 (Baculoviral IAP repeat containing 3)

HER-2 overexpression • HER-2 amplification • PIK3CA mutation • PD-L1 amplification

almost2years

PD-1-CD28 fusion protein strengthens mesothelin-specific TRuC T cells in preclinical solid tumor models. (PubMed, Cell Oncol (Dordr))

Together, these results demonstrate the therapeutic potential of PD-1-CD28 co-expression in TRuC T cells to prevent PD-L1-induced T cell hypofunction.

almost 2 years ago

Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker

PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • MSLN (Mesothelin) • CD28 (CD28 Molecule)

PD-1 expression • PD-L1 amplification

almost2years

A cell-laden hydrogel as prophylactic vaccine and anti-PD-L1 amplifier against autologous tumors. (PubMed, J Control Release)

Thus, without the need for precisely delivering immunoactivatory agents to tumor or locally remodeling tumor microenvironment, "priming" intractable or inaccessible tumors for subsequent ICB therapy could be achieved by prophylactic vaccination with (ACCO+CpG)@Gel. These findings highlighted (ACCO+CpG)@Gel as a generalized framework of protective vaccine strategy that could be broadly applicable to potentiate ICB therapy against multiple types of orthotopic tumors growing in different regions.

almost 2 years ago

Journal • PD(L)-1 Biomarker • IO biomarker

CD8 (cluster of differentiation 8)

PD-L1 expression • PD-L1 amplification