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| Profile Name | MSH6 negative |
| Gene Variant Detail | |
| Relevant Treatment Approaches | PD-L1/PD-1 antibody Ipilimumab + Nivolumab |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| MSH6 negative | ovarian cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as systemic therapy for patients with recurrent ovarian cancer with MSH6 deficiency (NCCN.org). | detail... |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | FDA approved - On Companion Diagnostic | Actionable | In a Phase I trial (GARNET) that supported FDA approval, Jemperli (dostarlimab-gxly) treatment demonstrated acceptable safety profile, and resulted in an objective response rate of 42.3% (30/71, 9 complete responses, 21 partial responses), with a median duration of response not reached in patients with recurrent or advanced endometrial cancer harboring mismatch repair deficiency (dMMR) as confirmed by a loss of MLH1, PMS2, MSH2, or MSH6 expression in an FDA-approved IHC test (PMID: 33001143; NCT02715284). | detail... 33001143 detail... |
| MSH6 negative | testicular germ cell cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as a third-line therapy for metastatic testicular germ cell cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | vulva squamous cell carcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as a second-line therapy for patients with MSI high or dMMR (often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) vulva squamous cell carcinoma (NCCN.org). | detail... |
| MSH6 negative | endometrial carcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as first-line or subsequent-line therapy (category 1) for patients with recurrent or metastatic endometrial carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | endometrial carcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as a second-line or subsequent-line therapy (category 1) for patients with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org). | detail... |
| MSH6 negative | endometrial carcinoma | sensitive | PD-L1/PD-1 antibody | Nivolumab | Guideline | Actionable | Opdivo (nivolumab) is included in guidelines as a second-line or subsequent-line therapy for patients with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org). | detail... |
| MSH6 negative | Advanced Solid Tumor | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | FDA approved - On Companion Diagnostic | Actionable | In a Phase I trial (GARNET) that supported FDA aproval, Jemperli (dostarlimab-gxly) treatment demonstrated acceptable safety profile, and resulted in an objective response rate of 41.6% (87/209), with a median duration of response not reached in patients with advanced mismatch repair deficient (dMMR) solid tumors, as indicated by a loss of MLH1, PMS2, MSH2, or MSH6 expression in an FDA-approved IHC test (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 2564-2564; NCT02715284). | detail... detail... detail... |
| MSH6 negative | esophageal cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as second-line or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) esophageal cancer that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org). | detail... |
| MSH6 negative | gastroesophageal junction adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as second-line or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) gastroesophageal junction cancer that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org). | detail... |
| MSH6 negative | stomach cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as second-line or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) stomach cancer that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org). | detail... |
| MSH6 negative | penile cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as subsequent-line systemic therapy for metastatic/recurrent penile cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | neuroendocrine tumor | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines for patients with locally advanced or metastatic well-differentiated, Grade 3 neuroendocrine tumors with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | chondrosarcoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic chondrosarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | osteosarcoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic osteosarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | Ewing sarcoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic Ewing sarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | chordoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic chordoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | colorectal cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | FDA approved | Actionable | In a Phase III (KEYNOTE-177) trial that supported FDA approval, Keytruda (pembrolizumab) treatment as first-line therapy significantly improved median progression-free survival (16.5 vs 8.2 mo, HR=0.60, p=0.0002) compared to chemotherapy in patients with advanced microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) colorectal cancer (PMID: 33264544; NCT02563002). | 33264544 detail... |
| MSH6 negative | breast cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines for patients with metastatic or unresectable breast cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) who have progressed on or following prior treatment (NCCN.org). | detail... |
| MSH6 negative | colon cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | prostate adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as a second-line therapy for patients with advanced or metastatic prostate adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | small intestine adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as an initial therapy for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | small intestine adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Nivolumab | Guideline | Actionable | Opdivo (nivolumab) is included in guidelines as an initial therapy for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | small intestine adenocarcinoma | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Opdivo (nivolumab) in combination with Yervoy (ipilimumab) is included in guidelines as an initial therapy for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | small intestine adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as a subsequent therapy for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | rectum cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | rectum cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as a preferred primary therapy for advanced or metastatic rectum cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | rectum cancer | sensitive | PD-L1/PD-1 antibody | Nivolumab | Guideline | Actionable | Opdivo (nivolumab) is included in guidelines as a primary therapy for advanced or metastatic rectum cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | rectum cancer | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Opdivo (nivolumab) in combination with Yervoy (ipilimumab) is included in guidelines as a primary therapy for advanced or metastatic rectum cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | hepatocellular carcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) hepatocellular carcinoma (NCCN.org). | detail... |
| MSH6 negative | endometrial carcinoma | sensitive | PD-L1/PD-1 antibody | Avelumab | Guideline | Actionable | Bavencio (avelumab) is included in guidelines as a second-line or subsequent-line therapy for patients with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org). | detail... |
| MSH6 negative | intrahepatic cholangiocarcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for intrahepatic cholangiocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | extrahepatic bile duct carcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for extrahepatic cholangiocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | gallbladder cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for gallbladder cancer patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | gallbladder cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as primary therapy for patients with unresectable or metastatic gallbladder cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), or as subsequent-line therapy (NCCN.org). | detail... |
| MSH6 negative | intrahepatic cholangiocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as primary therapy for patients with unresectable or metastatic intrahepatic cholangiocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), or as subsequent-line therapy (NCCN.org). | detail... |
| MSH6 negative | extrahepatic bile duct carcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as primary therapy for patients with unresectable or metastatic extrahepatic cholangiocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), or as subsequent-line therapy (NCCN.org). | detail... |
| MSH6 negative | Advanced Solid Tumor | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | FDA approved | Actionable | In a combined analysis of 5 trials that supported FDA approval, Keytruda (pembrolizumab) therapy resulted in an objective response rate of 39.6% (59/149) in advanced solid tumor patients with high levels of microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (PMID: 30787022; NCT01876511, NCT02460198, NCT01848834, NCT02054806, NCT02628067). | detail... 30787022 |
| MSH6 negative | colon cancer | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as primary or subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | colon cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as preferred primary or subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | colon cancer | sensitive | PD-L1/PD-1 antibody | Nivolumab | Guideline | Actionable | Opdivo (nivolumab) is included in guidelines as primary or subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | ovarian cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as systemic therapy for patients with recurrent or advanced ovarian cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | stomach cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced or metastatic gastric cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | germ cell cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as recurrence therapy for patients with germ cell tumors with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | esophageal cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | gastroesophageal junction adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | colorectal cancer | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | FDA approved | Actionable | In a Phase II (CheckMate 142) trial that supported FDA approval, Opdivo (nivolumab) and Yervoy (ipilimumab) combination treatment resulted in an objective response rate of 54.6% (65/119, 4 complete response, 61 partial response) and disease control over 12 weeks in 80% of patients with microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) metastatic colorectal cancer (PMID: 29355075; NCT02060188). | detail... detail... 29355075 |
| MSH6 negative | colorectal cancer | sensitive | PD-L1/PD-1 antibody | Nivolumab | FDA approved | Actionable | In a Phase II trial (CheckMate 142) that supported FDA approval, treatment with Opdivo (nivolumab) resulted in an objective response rate of 36% (19/53, 1 complete response, 18 partial responses) and disease control for 12 weeks or more in 70% (37/53) of patients with microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) metastatic colorectal cancer (PMID: 28734759; NCT02060188). | 28734759 detail... detail... |
| MSH6 negative | Adenocarcinoma of Unknown Primary | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines for patients with adenocarcinoma of unknown primary with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | Squamous Cell Carcinoma of Unknown Primary | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines for patients with squamous cell carcinoma of unknown primary with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | Adenocarcinoma of Unknown Primary | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines for patients with adenocarcinoma of unknown primary with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | endometrial carcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial (KEYNOTE-158) that supported FDA approval, Keytruda (pembrolizumab) treatment resulted in an objective response rate of 48% (38/79, 11 complete responses, 27 partial responses) in patients with advanced microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) endometrial carcinoma, with a median progression-free survival of 13.1 months (PMID: 34990208; NCT02628067). | detail... detail... 34990208 |
| MSH6 negative | pancreatic adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines for advanced or metastatic pancreatic adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | ampulla of Vater adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as first-line or subsequent therapy for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | ampulla of Vater adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | ampulla of Vater adenocarcinoma | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Opdivo (nivolumab) and (ipilimumab) combination therapy is included in guidelines as first-line or subsequent therapy for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | rectum cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Phase II | Actionable | In a Phase II trial, neoadjuvant Jemperli (dostarlimab-gxly) treatment resulted in an objective response of 100% (12/12, all complete responses) in patients with stage II or III rectal cancer with deficient mismatch repair (dMMR) as defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC (PMID: 35660797; NCT04165772). | 35660797 |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Avelumab | Guideline | Actionable | Bavencio (avelumab) is included in guidelines for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) endometrial cancer who have failed platinum-based therapy (PMID: 35690222; ESMO.org). | 35690222 detail... |
| MSH6 negative | endometrial cancer | predicted - sensitive | PD-L1/PD-1 antibody | Durvalumab | Guideline | Actionable | Imfinzi (durvalumab) is included in guidelines for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) endometrial cancer who have failed platinum-based therapy (PMID: 35690222; ESMO.org). | detail... 35690222 |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines for patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) endometrial cancer who have failed platinum-based therapy (PMID: 35690222; ESMO.org). | detail... 35690222 |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) endometrial cancer who have failed platinum-based therapy (PMID: 35690222; ESMO.org). | 35690222 detail... |
| MSH6 negative | endometrial cancer | predicted - sensitive | PD-L1/PD-1 antibody | Durvalumab | Phase II | Actionable | In a Phase II trial (PHAEDRA), Imfinzi (durvalumab) treatment resulted in superior objective tumor response rate (47%, 17/36, 6 complete responses, 11 partial responses (PR) vs 3%, 1/35, 1 PR) and median progression-free survival (8.3 vs 1.8 mo) in patients with mismatch repair deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) advanced endometrial cancer compared to mismatch repair proficient patients (PMID: 34103352; NCT03015129). | 34103352 |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Avelumab | Phase II | Actionable | In a Phase II trial, Bavencio (avelumab) treatment resulted in an objective response rate of 26.7% (4/15, 1 complete response, 3 partial responses) and 6-month progression-free survival rate of 40% (6/15) in patients with mismatch repair deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent or persistent endometrial cancer (PMID: 31461377; NCT02912572). | 31461377 |
| MSH6 negative | stomach cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as second-line therapy for patients with advanced or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) gastric cancer (PMID: 35914639; ESMO.org). | 35914639 detail... |
| MSH6 negative | gastroesophageal junction adenocarcinoma | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Phase II | Actionable | In a Phase II trial (NEONIPIGA), neoadjuvant Opdivo (nivolumab) and Yervoy (ipilimumab) followed by surgery led to a pathological complete response in 58.6% (17/29) of patients with resectable gastric/gastroesophageal junction adenocarcinoma with high microsatellite instability or deficient mismatch repair (dMMR) (defined by loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), and 30/31 patients in the per-protocol group were alive and progression-free at the time of analysis (PMID: 35969830; NCT0400626). | 35969830 |
| MSH6 negative | gastric adenocarcinoma | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Phase II | Actionable | In a Phase II trial (NEONIPIGA), neoadjuvant Opdivo (nivolumab) and Yervoy (ipilimumab) followed by surgery led to a pathological complete response in 58.6% (17/29) of patients with resectable gastric/gastroesophageal junction adenocarcinoma with high microsatellite instability or deficient mismatch repair (dMMR) (defined by loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), and 30/31 patients in the per-protocol group were alive and progression-free at the time of analysis (PMID: 35969830; NCT0400626). | 35969830 |
| MSH6 negative | cervical cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as preferred second-line or subsequent therapy for patients with cervical cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |