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Profile Name MLH1 negative
Gene Variant Detail

MLH1 negative (loss of function)

Relevant Treatment Approaches PD-L1/PD-1 antibody Ipilimumab + Nivolumab

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
MLH1 negative ovary epithelial cancer sensitive PD-L1/PD-1 antibody Pembrolizumab Guideline Actionable Keytruda (pembrolizumab) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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 approval, 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 negative neuroendocrine tumor sensitive PD-L1/PD-1 antibody Pembrolizumab Guideline Actionable Keytruda (pembrolizumab) is included in guidelines for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) locally advanced or metastatic well-differentiated, Grade 3 neuroendocrine tumors or unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms who have progressed on or following prior treatment (NCCN.org). detail...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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 cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). detail...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 negative ovary epithelial 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 epithelial ovarian, fallopian tube, or primary peritoneal 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...
MLH1 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...
MLH1 negative ovarian germ cell cancer sensitive PD-L1/PD-1 antibody Pembrolizumab Guideline Actionable Keytruda (pembrolizumab) is included in guidelines as recurrence therapy for patients with malignant ovarian 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...
MLH1 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...
MLH1 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...
MLH1 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... 29355075 detail...
MLH1 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). detail... 28734759 detail...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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... 34990208 detail...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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...
MLH1 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
MLH1 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). 35690222 detail...
MLH1 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...
MLH1 negative endometrial cancer 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). 35690222 detail...
MLH1 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...
MLH1 negative endometrial cancer 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
MLH1 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
MLH1 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...
MLH1 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
MLH1 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
MLH1 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...