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Profile Name PBRM1 loss
Gene Variant Detail

PBRM1 loss (loss of function)

Relevant Treatment Approaches EZH2 inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
PBRM1 A249fs clear cell renal cell carcinoma no benefit Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) treatment resulted in progressive disease in a patient with renal clear cell carcinoma harboring PBRM1 A249fs (PMID: 29301960). 29301960
PBRM1 K621* clear cell renal cell carcinoma no benefit Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) treatment resulted in progressive disease in a patient with renal clear cell carcinoma harboring PBRM1 K621* (PMID: 29301960). 29301960
PBRM1 S681R clear cell renal cell carcinoma predicted - sensitive Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) treatment resulted in partial response in a patient with renal clear cell carcinoma harboring PBRM1 S681R (PMID: 29301960). 29301960
PBRM1 mutant clear cell renal cell carcinoma predicted - sensitive Nivolumab Clinical Study - Cohort Actionable In a clinical study, PBRM1 truncating mutations were associated with response to Opdivo (nivolumab) with 39% (15/38) of responding patients harboring PBRM1 mutations vs 22% (16/74) of non-responders, as well as clinical benefit (p=0.0497), increased progression-free survival (HR=0.67), and overall survival (HR=0.65) in post-hoc analysis of archival samples from a Phase III clinical trial of clear cell renal cell carcinoma patients (PMID: 31486842). 31486842
PBRM1 mutant clear cell renal cell carcinoma conflicting Everolimus Clinical Study - Cohort Actionable In a clinical study, PBRM1 truncating mutations were not associated with progression-free survival or overall survival in clear cell renal cell carcinoma patients treated with Afinitor (everolimus) (n=193) (PMID: 31486842). 31486842
PBRM1 mutant clear cell renal cell carcinoma conflicting Everolimus Phase II Actionable In a Phase II trial (RECORD-3), PBRM1 mutations were associated with longer first-line progression free survival (12.8 vs 5.5 months) in first-line Afinitor (everolimus)-treated clear cell renal cell carcinoma patients compared to first-line Sutent (sunitinib)-treated patients (PMID: 27751729). 27751729
PBRM1 inact mut clear cell renal cell carcinoma sensitive Atezolizumab Clinical Study - Cohort Actionable In a clinical study, renal clear cell carcinoma patients harboring PBRM1 loss-of-function mutations demonstrated improved response to immune checkpoint therapies including Opdivo (nivolumab) alone or in combination with Yervoy (ipilimumab), and Tecentriq (atezolizumab), potentially due to the distinct expression profile of immune-related genes in these patients (PMID: 29301960). 29301960
PBRM1 inact mut transitional cell carcinoma not predictive unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including PBRM1, did not correlate with improved survival in 2 separate cohorts of patients with transitional cell carcinoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 1.44 (p=0.34, n=56) and 0.82 (p=0.559, n=93), respectively (PMID: 32321774). 32321774
PBRM1 inact mut clear cell renal cell carcinoma sensitive Nivolumab Clinical Study - Cohort Actionable In a clinical study, renal clear cell carcinoma patients harboring PBRM1 loss-of-function mutations demonstrated improved response to immune checkpoint therapies including Opdivo (nivolumab) alone or in combination with Yervoy (ipilimumab), and Tecentriq (atezolizumab), potentially due to the distinct expression profile of immune-related genes in these patients (PMID: 29301960). 29301960
PBRM1 inact mut kidney cancer predicted - sensitive EZH2 inhibitor GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 inhibited growth of 3/4 tested renal cancer cell lines harboring PBRM1 inactivating mutations in culture, with inhibitor sensitivity associating with dependence on EZH2 catalytic activity (PMID: 26552009). 26552009
PBRM1 inact mut renal cell carcinoma no benefit GDC-0980 Phase II Actionable In a retrospective analysis from a Phase II clinical trial, patients with renal cell carcinoma treated with Apitolisib (GDC-0980) had no difference in progression free survival when stratified by the presence (n=5) or absence (n=17) of deleterious PBRM1 mutations (PMID: 26951309). 26951309
PBRM1 inact mut colorectal adenocarcinoma unknown unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including PBRM1, correlated with improved survival in one cohort of patients with colorectal adenocarcinoma treated with systemic immune checkpoint inhibitors but not the other, with adjusted HRs for overall survival of 0.30 (p=0.03, n=35) and 0.56 (p=0.244, n=63), respectively (PMID: 32321774). 32321774
PBRM1 inact mut clear cell renal cell carcinoma sensitive Ipilimumab + Nivolumab Clinical Study - Cohort Actionable In a clinical study, renal clear cell carcinoma patients harboring PBRM1 loss-of-function mutations demonstrated improved response to immune checkpoint therapies including Opdivo (nivolumab) alone or in combination with Yervoy (ipilimumab), and Tecentriq (atezolizumab), potentially due to the distinct expression profile of immune-related genes in these patients (PMID: 29301960). 29301960
PBRM1 inact mut head and neck squamous cell carcinoma not predictive unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including PBRM1, did not correlate with improved survival in 2 separate cohorts of patients with head and neck squamous cell carcinoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 0.74 (p=0.631, n=31) and 0.76 (p=0.622, n=68), respectively (PMID: 32321774). 32321774
PBRM1 inact mut gastroesophageal adenocarcinoma not predictive unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including PBRM1, did not correlate with improved survival in 2 separate cohorts of patients with gastroesophageal adenocarcinoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 0.70 (p=0.403, n=66) and 0.46 (p=0.071, n=59), respectively (PMID: 32321774). 32321774
PBRM1 inact mut renal cell carcinoma no benefit Everolimus Phase II Actionable In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma had no difference in progression free survival when stratified by the presence (n=6) or absence (n=22) of deleterious PBRM1 mutation when treated with Afinitor (everolimus) (PMID: 26951309). 26951309
PBRM1 inact mut melanoma not predictive unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including PBRM1, did not correlate with improved survival in 2 separate cohorts of patients with melanoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 1.70 (p=0.192, n=86) and 1.02 (p=0.939, n=192), respectively (PMID: 32321774). 32321774
PBRM1 Y608fs clear cell renal cell carcinoma no benefit Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) treatment resulted in progressive disease in a patient with renal clear cell carcinoma harboring PBRM1 Y608fs (PMID: 29301960). 29301960
PBRM1 K154fs clear cell renal cell carcinoma predicted - sensitive Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) treatment resulted in partial response in a patient with renal clear cell carcinoma harboring PBRM1 K154fs (PMID: 29301960). 29301960
PBRM1 loss melanoma sensitive unspecified CTLA4 antibody + unspecified PD-1 antibody Preclinical - Cell line xenograft Actionable In a preclinical study, knocking-out PBRM1 in melanoma cells sensitized cells to immune therapy consisted of anti-CTLA4 and anti-PD-1 antibodies in culture and in cell line xenograft models, potentially due to increased sensitivity to T cell-mediated cytotoxicity and a favorable tumor microenvironment (PMID: 29301958). 29301958
PBRM1 Y106* clear cell renal cell carcinoma predicted - sensitive Ipilimumab + Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) and Yervoy (ipilimumab) combination treatment resulted in complete response in a patient with renal clear cell carcinoma harboring PBRM1 Y106* (PMID: 29301960). 29301960
PBRM1 Y331* clear cell renal cell carcinoma predicted - sensitive Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) treatment resulted in complete response in a patient with renal clear cell carcinoma harboring PBRM1 Y331* (PMID: 29301960). 29301960
PBRM1 N463fs clear cell renal cell carcinoma predicted - sensitive Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) treatment resulted in partial response in a patient with renal clear cell carcinoma harboring PBRM1 N463fs (PMID: 29301960). 29301960
PBRM1 E291* clear cell renal cell carcinoma no benefit Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) treatment resulted in progressive disease in a patient with renal clear cell carcinoma harboring PBRM1 E291* (PMID: 29301960). 29301960
PBRM1 W141_L145delinsC clear cell renal cell carcinoma no benefit Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) treatment resulted in progressive disease in a patient with renal clear cell carcinoma harboring PBRM1 W141_L145delinsC (PMID: 29301960). 29301960
PBRM1 G2fs clear cell renal cell carcinoma no benefit Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) treatment resulted in progressive disease in a patient with renal clear cell carcinoma harboring PBRM1 G2fs (PMID: 29301960). 29301960
PBRM1 K135fs clear cell renal cell carcinoma predicted - sensitive Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) treatment resulted in stable disease in a patient with renal clear cell carcinoma harboring PBRM1 K135fs (PMID: 29301960). 29301960
PBRM1 K619fs clear cell renal cell carcinoma predicted - sensitive Ipilimumab + Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) and Yervoy (ipilimumab) combination treatment resulted in partial response in a patient with renal clear cell carcinoma harboring PBRM1 K619fs (PMID: 29301960). 29301960
PBRM1 N609fs clear cell renal cell carcinoma no benefit Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) treatment resulted in progressive disease in a patient with renal clear cell carcinoma harboring PBRM1 N609fs (PMID: 29301960). 29301960
PBRM1 R941fs clear cell renal cell carcinoma no benefit Nivolumab Case Reports/Case Series Actionable In a clinical study, Opdivo (nivolumab) treatment resulted in progressive disease in a patient with renal clear cell carcinoma harboring PBRM1 R941fs (PMID: 29301960). 29301960
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries