News - FANCA deletion

7d

Utility of Clinical Next Generation Sequencing Tests in KIT/PDGFRA/SDH Wild-Type Gastrointestinal Stromal Tumors. (PubMed, Cancers (Basel))

Compared to KIT/PDGFRA-mutant GIST, limited benefit was observed with imatinib in triple-negative GIST. In depth molecular profiling can be helpful in identifying driver mutations and guiding therapy.

7 days ago

Journal • Next-generation sequencing • Stroma

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BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • ETV6 (ETS Variant Transcription Factor 6) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • AURKA (Aurora kinase A) • SDHC (Succinate Dehydrogenase Complex Subunit C) • SDHD (Succinate Dehydrogenase Complex Subunit D) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

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TP53 mutation • BRAF V600E • BRAF V600 • NTRK3 fusion • PTEN deletion • PTEN mutation • NF1 mutation • ETV6-NTRK3 fusion • CHEK2 mutation • PDGFRA mutation • FANCA mutation • FGFR1 fusion • FANCA deletion • PDGFR wild-type

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imatinib

3ms

A Study of Olaparib and Durvalumab in Prostate Cancer (clinicaltrials.gov)

P2, N=5, Terminated, Memorial Sloan Kettering Cancer Center | Completed --> Terminated; Due to low accrual

3 months ago

Trial termination • Metastases

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • FANCA deletion

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Lynparza (olaparib) • Imfinzi (durvalumab)

7ms

Assessment of Optical Genome Mapping for Front-Line Diagnostic Evaluation of Acute Leukemia: A Canadian Single-Center Evaluation of Added Yield in 69 Informative Cases (ASH 2023)

High-resolution genome-wide evaluation not reliant on cell culture substantially expands the scope of detectable variants, for many of which determining the biologic and clinical implications will require larger scale prospective study. Importantly, application of OGM in the clinical setting is likely to result in clinically meaningful disease reclassification and restratification of risk, and in some cases may permit patients access to previously inaccessible targeted therapies (as in the instance of cytogenetically cryptic tyrosine kinase gene fusions).

7 months ago

Clinical

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TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6) • FANCA (FA Complementation Group A) • PAX5 (Paired Box 5) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MECOM (MDS1 And EVI1 Complex Locus) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • AFDN (Afadin, Adherens Junction Formation Factor)

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KMT2A rearrangement • MLL rearrangement • FLT3 overexpression • FANCA deletion

9ms

DOLAF: Durvalumab, With Olaparib and Fulvestrant in Advanced ER+, HER2- Breast Cancer Patients. (clinicaltrials.gov)

P2, N=172, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting

9 months ago

Enrollment closed • Metastases

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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)

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ER positive • BRCA1 mutation • HER-2 negative • FANCA deletion

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Lynparza (olaparib) • Imfinzi (durvalumab) • fulvestrant

10ms

A Study of Olaparib and Durvalumab in Prostate Cancer (clinicaltrials.gov)

P2, N=5, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Feb 2024 --> Jul 2023 | Trial primary completion date: Feb 2024 --> Jul 2023

10 months ago

Trial completion • Trial completion date • Trial primary completion date • Metastases

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PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • FANCA deletion

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Lynparza (olaparib) • Imfinzi (durvalumab)

1year

A Study of Olaparib and Durvalumab in Prostate Cancer (clinicaltrials.gov)

P2, N=5, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2023 --> Feb 2024 | Trial primary completion date: Feb 2023 --> Feb 2024

1 year ago

Trial completion date • Trial primary completion date • Metastases

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PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • FANCA deletion

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Lynparza (olaparib) • Imfinzi (durvalumab)

over1year

DOLAF: Durvalumab, With Olaparib and Fulvestrant in Advanced ER+, HER2- Breast Cancer Patients. (clinicaltrials.gov)

P2, N=158, Recruiting, UNICANCER | Trial primary completion date: Sep 2022 --> Aug 2023

over 1 year ago

Trial primary completion date • Metastases

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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)

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ER positive • BRCA1 mutation • HER-2 negative • FANCA deletion

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Lynparza (olaparib) • Imfinzi (durvalumab) • fulvestrant

almost2years

LODESTAR: A Study to Evaluate Rucaparib in Patients With Solid Tumors and With Deleterious Mutations in HRR Genes (clinicaltrials.gov)

P2, N=83, Terminated, Clovis Oncology, Inc. | N=220 --> 83 | Active, not recruiting --> Terminated; The study was terminated due to a change in development priorities.

almost 2 years ago

Enrollment change • Trial termination

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

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BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • NBN mutation • FANCA deletion • RAD51 mutation

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Rubraca (rucaparib)

almost2years

Targeting genome integrity dysfunctions impedes metastatic potency in non-small-cell lung cancer circulating tumor cell-derived eXplants. (PubMed, JCI Insight)

GR-CDXL1 presented homologous recombination deficiency linked to biallelic BRCA2 mutation and FANCA deletion, unrepaired DNA lesions after mitosis, and olaparib sensitivity, despite resistance to chemotherapy...Centrosome clustering promoted targetable chromosomal instability in GR-CDXL3 cells. These CDX unravel DDR and genome integrity-related defects as a central mechanism underpinning metastatic potency of CTCs and provide rationale for their therapeutic targeting in metastatic NSCLC.

almost 2 years ago

Journal • Circulating Tumor Cells • BRCA Biomarker • PARP Biomarker

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BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • SLFN11 (Schlafen Family Member 11) • FANCA (FA Complementation Group A) • CDX2 (Caudal Type Homeobox 2)

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BRCA2 mutation • HRD • SLFN11 expression • FANCA mutation • SLFN11 overexpression • FANCA deletion

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Lynparza (olaparib)

2years

A Study of Olaparib and Durvalumab in Prostate Cancer (clinicaltrials.gov)

P2, N=5, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=32 --> 5

2 years ago

Enrollment closed • Enrollment change

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PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • FANCA deletion

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Lynparza (olaparib) • Imfinzi (durvalumab)

2years

LODESTAR: A Study to Evaluate Rucaparib in Patients With Solid Tumors and With Deleterious Mutations in HRR Genes (clinicaltrials.gov)

P2, N=220, Active, not recruiting, Clovis Oncology, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Mar 2023 --> Jun 2022 | Trial primary completion date: Dec 2022 --> May 2022

2 years ago

Enrollment closed • Trial completion date • Trial primary completion date

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

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BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • NBN mutation • FANCA deletion • RAD51 mutation

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Rubraca (rucaparib)

2years

Circulating tumor cell-derived explant models reveal DNA damage response-based therapeutic opportunities in non-small cell lung cancer (AACR 2022)

This study unravels distinct DDR profiles as a central mechanism underpinning CTC metastatic potency. Our CDX models provide a robust platform for ex vivo drug testing of DDR-targeted strategies to expand patient categories that may benefit from precision medicine in metastatic NSCLC.

2 years ago

Circulating Tumor Cells • BRCA Biomarker • PARP Biomarker

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BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • SLFN11 (Schlafen Family Member 11) • FANCA (FA Complementation Group A) • CDX2 (Caudal Type Homeobox 2)

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BRCA2 mutation • HRD • SLFN11 expression • FANCA mutation • SLFN11 overexpression • FANCA deletion

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Lynparza (olaparib)

over2years

LODESTAR: A Study to Evaluate Rucaparib in Patients With Solid Tumors and With Deleterious Mutations in HRR Genes (clinicaltrials.gov)

P2, N=220, Recruiting, Clovis Oncology, Inc. | Trial completion date: May 2022 --> Mar 2023 | Trial primary completion date: Nov 2021 --> Dec 2022

over 2 years ago

Trial completion date • Trial primary completion date

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

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BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • NBN mutation • FANCA deletion • RAD51 mutation

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Rubraca (rucaparib)

over2years

DOLAF: Durvalumab, With Olaparib and Fulvestrant in Advanced ER+, HER2- Breast Cancer Patients. (clinicaltrials.gov)

P2, N=158, Recruiting, UNICANCER | Trial completion date: Aug 2025 --> Aug 2027 | Trial primary completion date: Mar 2022 --> Sep 2022

over 2 years ago

Clinical • Trial completion date • Trial primary completion date

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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)

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ER positive • BRCA1 mutation • HER-2 negative • FANCA deletion

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Lynparza (olaparib) • Imfinzi (durvalumab) • fulvestrant

over2years

A Study of Olaparib and Durvalumab in Prostate Cancer (clinicaltrials.gov)

P2, N=32, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2022 --> Feb 2023 | Trial primary completion date: Feb 2022 --> Feb 2023

over 2 years ago

Trial completion date • Trial primary completion date

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PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • FANCA deletion

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Lynparza (olaparib) • Imfinzi (durvalumab)

over3years

Efficacy of chemotherapy combined with toripalimab in PD-L1-positive and high tumor mutation burden pancreatic acinar cell carcinoma: case report. (PubMed, Tumori)

Starting from April 2019, a patient first received chemotherapy with two cycles of gemcitabine and nab-paclitaxel and two cycles of SOX regimen. Time from initiating treatment to tumor progression on toripalimab and SOX regimen treatment took up to at least 8 months. We present the first case report where a PD-L1 positive, high TMB, and FANCA-deleted pancreatic acinar cell carcinoma was treated using chemotherapy combined with immunotherapy, in which the patient exhibited satisfactory response and tolerance.

over 3 years ago

Clinical • Journal • Tumor Mutational Burden • PD(L)-1 Biomarker

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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • FANCA (FA Complementation Group A)

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PD-L1 expression • TMB-H • FANCA mutation • FANCA deletion

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gemcitabine • Loqtorzi (toripalimab-tpzi) • albumin-bound paclitaxel

over3years

A Study of Olaparib and Durvalumab in Prostate Cancer (clinicaltrials.gov)

P2, N=32, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2021 --> Feb 2022 | Trial primary completion date: Feb 2021 --> Feb 2022

over 3 years ago

Trial completion date • Trial primary completion date • PARP Biomarker • PD(L)-1 Biomarker

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PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • FANCA deletion

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Lynparza (olaparib) • Imfinzi (durvalumab)

over3years

[VIRTUAL] Dolaf- an international multicenter phase 2 trial of durvalumab (medi4736) plus olaparib plus fulvestrant in metastatic or locally advanced erpositive, her2-negative breast cancer patients selected using criteria that predict sensitivity to olaparib (UCBG308) (SABCS 2020)

The safety run-in is over. By July 1, 2020, 62 patients have been screened and 8 have been treated (NCT04053322).

over 3 years ago

Clinical • P2 data • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker

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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2)

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BRCA2 mutation • ER positive • BRCA1 mutation • HER-2 negative • BRCA1 mutation + BRCA2 mutation • BRCA mutation • FANCA deletion

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Lynparza (olaparib) • Imfinzi (durvalumab)

over3years

Platinum-Based Chemotherapy in Metastatic Prostate Cancer With DNA Repair Gene Alterations. (PubMed, JCO Precis Oncol)

Patients with DDRmut disease had better response to platinum-based chemotherapy, suggesting that DDR status warrants prospective validation as a potential biomarker for patient selection. Responses to platinum chemotherapy were observed in BRCA-altered prostate cancer after PARPi progression. Additional studies are needed to determine the predictive role of individual genes on platinum sensitivity in the context of other clinical and genomic factors.

over 3 years ago

Journal • BRCA Biomarker • PARP Biomarker

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • FANCA (FA Complementation Group A) • KLK3 (Kallikrein-related peptidase 3)

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PALB2 mutation • FANCA deletion