IDH1 R132S
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 28.6% (8/28), CR with partial hematological recovery (CRh) in 14.3% (4/28) of patients age 75 or older with untreated acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a median treatment duration of 4.3 months (PMID: 29860938; NCT02074839).
|
detail...
29860938
detail...
|
ALK fusion
|
lung non-small cell carcinoma
|
sensitive
|
Lorlatinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (Study B7461006) that supported FDA approval, Lorbrena (lorlatinib) treatment significantly improved 12-month progression-free survival rate (78% vs 39%, HR 0.28, p<0.001) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer who had no prior systemic therapy, objective response rate was 82% (57/69) with 71% achieved complete intracranial response in patients with brain metastasis (PMID: 33207094; NCT03052608).
|
33207094
detail...
detail...
|
BRAF V600K
|
melanoma
|
sensitive
|
Binimetinib + Encorafenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) resulted in a median overall survival (OS) of 33.6 months, a 1-year OS rate of 77.5%, and a 2-year OS rate of 57.7% in patients with advanced melanoma harboring BRAF V600E/K mutations compared to a median OS of 16.9 months and 1- and 2-year OS rates of 63.1% and 43.2%, respectively, in the Zelboraf (vemurafenib) treated group (PMID: 30219628; NCT01909453).
|
detail...
30219628
detail...
detail...
|
BRAF V600E/K
|
melanoma
|
sensitive
|
Cobimetinib + Vemurafenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (coBRIM) that supported FDA approval, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf (vemurafenib) plus placebo, among patients with BRAF V600-mutated metastatic melanoma, and BRAF V600E and BRAF V600K are on the companion diagnostic (PMID: 27480103; NCT01689519).
|
detail...
detail...
27480103
|
FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Cytarabine + Daunorubicin + Midostaurin
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase III trial that supported FDA approval, treatment with Rydapt (midostaurin), combined with Cytosar-U (cytarabine) and Daunorubicin, improved overall survival (HR=0.78, p=0.009) and event-free survival (HR=0.78, p=0.002) in patients with FLT3-mutant (ITD, D835X, and I836X mutations) acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114; NCT00651261).
|
28644114
detail...
detail...
|
ALK rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Brigatinib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501).
|
detail...
detail...
detail...
|
IDH1 mutant
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 21.6% (27/125), CR with partial hematological recovery (CRh) in 8.8% (11/125), and overall response (OR) in 41.6% (52/125) of patients with relapsed or refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test (PMID: 29860938; NCT02074839).
|
detail...
detail...
29860938
|
FGFR3 S249C
|
bladder urothelial carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3 S249C is included in the companion diagnostic (PMID: 31340094; NCT02365597).
|
detail...
31340094
detail...
|
RAD54L inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved progression-free survival (PFS, 5.8 vs 3.5 mo, HR=0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, including patients harboring RAD54L mutations (7.20 vs 2.41 mo) (PMID: 32343890; NCT02987543).
|
detail...
detail...
32343890
|
ALK fusion
|
lung non-small cell carcinoma
|
sensitive
|
Lorlatinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865).
|
detail...
30413378
detail...
|
CHEK2 inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved progression-free survival (PFS, 5.8 vs 3.5 mo, HR=0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, including patients harboring CHEK2 mutations (5.59 vs 3.35 mo) (PMID: 32343890; NCT02987543).
|
detail...
detail...
32343890
|
BRAF V600E/K
|
melanoma
|
sensitive
|
Trametinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K positive metastatic melanoma (PMID: 22663011; NCT01245062).
|
22663011
detail...
detail...
|
PALB2 inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved progression-free survival (PFS, 5.8 vs 3.5 mo, HR=0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, including patients harboring PALB2 mutations (PMID: 32343890; NCT02987543).
|
detail...
detail...
32343890
|
BRIP1 inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved progression-free survival (PFS, 5.8 vs 3.5 mo, HR=0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, including patients harboring BRIP1 mutations (PMID: 32343890; NCT02987543).
|
detail...
32343890
detail...
|
BRAF V600E
|
thyroid gland anaplastic carcinoma
|
sensitive
|
Dabrafenib + Trametinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (ROAR) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an overall response rate of 69% (11/16; 1 complete response and 10 partial responses) in patients with anaplastic thyroid cancer harboring BRAF V600E (PMID: 29072975; NCT02034110).
|
29072975
detail...
detail...
|
MLH1 negative
|
endometrial carcinoma
|
sensitive
|
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...
|
BRAF V600E/K
|
melanoma
|
sensitive
|
Binimetinib + Encorafenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) demonstrated improved tolerability profile and efficacy, resulted in a progression-free survival of 14.9 months in patients with advanced melanoma harboring BRAF V600E/K mutations, comparing to 7.3 months in the Zelboraf (vemurafenib) group (HR=0.54, p<0.0001) (PMID: 29573941; NCT01909453) and both BRAF V600E and V600K are on the companion diagnostic.
|
29573941
detail...
detail...
detail...
|
BRAF V600E
|
melanoma
|
sensitive
|
Dabrafenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III clinical trial (BREAK-3) that supported FDA approval, Tafinlar (dabrafenib) improved median progression-free survival compared to Deticene (dacarbazine) (5.1 vs 2.7 months, HR=0.3, p<0.0001) in patients with BRAF V600E positive melanoma (PMID: 22735384; NCT01227889).
|
detail...
detail...
22735384
|
IDH1 R132S
|
cholangiocarcinoma
|
predicted - sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III (ClarIDHy) trial that supported FDA approval, Tibsovo (ivosidenib) treatment significantly improved median progression-free survival (2.7 vs 1.4 mo, HR=0.37, p<0.001) and prolonged median overall survival (10.8 vs 9.7 mo, HR=0.69, p=0.06) compared to placebo in patients with advanced cholangiocarcinoma harboring IDH1 mutations including R132C/H/L/G/S, resulted in favorable objective response rate (2%, 3/124 vs 0%, 0/61) and stable disease rate (51% vs 28%) (PMID: 32416072; NCT02989857).
|
detail...
detail...
32416072
|
FGFR3 G370C
|
transitional cell carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3 G370C is included in the companion diagnostic (PMID: 31340094; NCT02365597).
|
detail...
31340094
detail...
|
FANCL inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved progression-free survival (PFS, 5.8 vs 3.5 mo, HR=0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, including patients harboring FANCL mutations (PMID: 32343890; NCT02987543).
|
detail...
detail...
32343890
|
BRAF V600E
|
melanoma
|
sensitive
|
Dabrafenib + Trametinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (COMBI-v) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved overall survival rate at 12 months (72% vs 65%, HR=0.69, p=0.005), median progression-free survival (11.4 vs 7.3 months, HR=0.56, p<0.001), and objective response rate (64% vs 51%, p<0.001) compared to Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (PMID: 25399551; NCT01597908).
|
detail...
detail...
25399551
|
BRAF V600E
|
melanoma
|
sensitive
|
Binimetinib + Encorafenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) resulted in a median overall survival (OS) of 33.6 months, a 1-year OS rate of 77.5%, and a 2-year OS rate of 57.7% in patients with advanced melanoma harboring BRAF V600E/K mutations compared to a median OS of 16.9 months and 1- and 2-year OS rates of 63.1% and 43.2%, respectively, in the Zelboraf (vemurafenib) treated group (PMID: 30219628; NCT01909453).
|
detail...
30219628
detail...
detail...
|
FGFR3 mutant
|
transitional cell carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (PMID: 31340094; NCT02365597).
|
detail...
31340094
detail...
|
IDH1 R132C
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 21.6% (27/125), CR with partial hematological recovery (CRh) in 8.8% (11/125), and overall response (OR) in 41.6% (52/125) of patients with relapsed or refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test (PMID: 29860938; NCT02074839).
|
detail...
detail...
detail...
29860938
|
FLT3 exon 14 ins
|
acute myeloid leukemia
|
sensitive
|
Cytarabine + Daunorubicin + Midostaurin
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial that supported FDA approval, treatment with Rydapt (midostaurin), combined with Cytosar-U (cytarabine) and Daunorubicin, improved overall survival (74.7 mo vs 25.6 mo) in patients with FLT3-mutant (D835X and I836X) or FLT3-ITD (exon 14 insertions) acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114).
|
28644114
detail...
detail...
|
FGFR2 rearrange
|
cholangiocarcinoma
|
sensitive
|
Infigratinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial that supported FDA approval, Truseltiq (infigratinib) treatment demonstrated manageable toxicity, resulted in an objective response rate of 23.1% (25/108, 1 complete response, 24 partial responses) in patients with previously treated advanced cholangiocarcinoma harboring an FGFR2 fusion or rearrangement, with a median duration of response of 5.0 months and a median progression-free survival of 7.3 months (J Clin Oncol 39, no. 3_suppl (January 20, 2021) 265-265; NCT02150967).
|
detail...
detail...
detail...
|
IDH1 R132G
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 21.6% (27/125), CR with partial hematological recovery (CRh) in 8.8% (11/125), and overall response (OR) in 41.6% (52/125) of patients with relapsed or refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test (PMID: 29860938; NCT02074839).
|
detail...
29860938
detail...
|
FGFR2 mutant
|
bladder urothelial carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (PMID: 31340094; NCT02365597).
|
detail...
31340094
detail...
|
ALK rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Lorlatinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865).
|
detail...
detail...
30413378
|
IDH2 R140G
|
acute myeloid leukemia
|
sensitive
|
Enasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R140G is on the companion diagnostic.
|
detail...
detail...
28588020
|
BRAF V600K
|
melanoma
|
sensitive
|
Trametinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K-positive metastatic melanoma (PMID: 22663011; NCT01245062).
|
22663011
detail...
detail...
|
BRAF V600E
|
melanoma
|
sensitive
|
Binimetinib + Encorafenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) demonstrated improved tolerability profile and efficacy, resulted in a progression-free survival of 14.9 months in patients with advanced melanoma harboring BRAF V600E/K mutations, comparing to 7.3 months in the Zelboraf (vemurafenib) group (HR=0.54, p<0.0001) (PMID: 29573941; NCT01909453), and both BRAF V600E and V600K are on the companion diagnostic.
|
29573941
detail...
detail...
detail...
|
RAD51C inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved progression-free survival (PFS, 5.8 vs 3.5 mo, HR=0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, including patients harboring RAD51C mutations (PMID: 32343890; NCT02987543).
|
detail...
detail...
32343890
|
FGFR3 G370C
|
bladder urothelial carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3 G370C is included in the companion diagnostic (PMID: 31340094; NCT02365597).
|
detail...
31340094
detail...
|
RET fusion
|
lung non-small cell carcinoma
|
sensitive
|
Pralsetinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I/II trial (ARROW) that supported FDA approval, Gavreto (pralsetinib) treatment was well-tolerated, resulting in an objective response rate of 61% (53/87) and 70% (19/27) in previously treated and treatment-naive patients with RET fusion-positive non-small cell lung cancer, respectively (PMID: 34118197; NCT03037385).
|
detail...
34118197
detail...
|
FGFR3 - TACC3
|
transitional cell carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3-TACC3 v1 and v3 fusions are included in the companion diagnostic (PMID: 31340094; NCT02365597).
|
detail...
31340094
detail...
|
FGFR3 R248C
|
bladder urothelial carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3 R248C is included in the companion diagnostic (PMID: 31340094; NCT02365597).
|
detail...
31340094
detail...
|
IDH1 R132G
|
cholangiocarcinoma
|
predicted - sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III (ClarIDHy) trial that supported FDA approval, Tibsovo (ivosidenib) treatment significantly improved median progression-free survival (2.7 vs 1.4 mo, HR=0.37, p<0.001) and prolonged median overall survival (10.8 vs 9.7 mo, HR=0.69, p=0.06) compared to placebo in patients with advanced cholangiocarcinoma harboring IDH1 mutations including R132C/H/L/G/S, resulted in favorable objective response rate (2%, 3/124 vs 0%, 0/61) and stable disease rate (51% vs 28%) (PMID: 32416072; NCT02989857).
|
detail...
32416072
detail...
|
IDH2 R140Q
|
acute myeloid leukemia
|
sensitive
|
Enasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R140Q is on the companion diagnostic.
|
detail...
detail...
28588020
|
BRAF V600E
|
melanoma
|
sensitive
|
Vemurafenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (BRIM-3) that supported FDA approval, Zelboraf (vemurafenib), as compared to Deticene (dacarbazine), resulted in an improved overall survival (OS) (13.6 vs 9.7 months, HR=0.81, p=0.03) in patients with BRAF V600E-positive metastatic melanoma, with estimated OS rates of 56%, 30%, 21%, and 17% at 1, 2, 3, and 4 years, respectively (PMID: 28961848, PMID: 21639808; NCT01006980), and BRAF V600E is included on the companion diagnostic (FDA.gov).
|
28961848
detail...
detail...
21639808
|
BARD1 inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved progression-free survival (PFS, 5.8 vs 3.5 mo, HR=0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, including patients harboring BARD1 mutations (PMID: 32343890; NCT02987543).
|
detail...
32343890
detail...
|
IDH2 R172W
|
acute myeloid leukemia
|
sensitive
|
Enasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172W is on the companion diagnostic.
|
28588020
detail...
detail...
|
IDH1 R132G
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 28.6% (8/28), CR with partial hematological recovery (CRh) in 14.3% (4/28) of patients age 75 or older with untreated acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a median treatment duration of 4.3 months (PMID: 29860938; NCT02074839).
|
detail...
29860938
detail...
|
IDH1 R132L
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 21.6% (27/125), CR with partial hematological recovery (CRh) in 8.8% (11/125), and overall response (OR) in 41.6% (52/125) of patients with relapsed or refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test (PMID: 29860938; NCT02074839).
|
29860938
detail...
detail...
|
IDH2 R140W
|
acute myeloid leukemia
|
sensitive
|
Enasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R140W is on the companion diagnostic.
|
detail...
detail...
28588020
|
FGFR2 fusion
|
cholangiocarcinoma
|
sensitive
|
Pemigatinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II (FIGHT-202) trial, Pemazyre (pemigatinib) treatment resulted in an objective response in 35.5% (38/107, 3 complete response, 35 partial response) of patients with advanced cholangiocarcinoma harboring FGFR2 fusions or rearrangements, with a disease control rate of 82% (88/107), median time-to-response of 2.7 months, and a median progression-free survival of 6.9 months (PMID: 32203698; NCT02924376).
|
detail...
32203698
detail...
|
IDH2 R172G
|
acute myeloid leukemia
|
sensitive
|
Enasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172G is on the companion diagnostic.
|
28588020
detail...
detail...
|
BRAF V600E
|
lung non-small cell carcinoma
|
sensitive
|
Dabrafenib + Trametinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial that supported FDA approval, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) in patients with non-small cell lung cancer harboring BRAF V600E resulted in an overall response rate of 66.7% (38/57) in previously treated patients and 64% (23/36) in untreated patients, versus 33% (26/78) treated with Tafinlar (dabrafenib) alone (PMID: 27080216, PMID: 27283860, PMID: 28919011; NCT01336634).
|
27283860
detail...
27080216
detail...
detail...
28919011
|
MLH1 negative
|
Advanced Solid Tumor
|
predicted - sensitive
|
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...
|
BRAF V600K
|
melanoma
|
sensitive
|
Cobimetinib + Vemurafenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (coBRIM) that supported FDA approval, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf (vemurafenib) plus placebo, among patients with BRAF V600-mutated metastatic melanoma, and BRAF V600E and BRAF V600K are on the companion diagnostic (PMID: 27480103; NCT01689519).
|
detail...
27480103
detail...
|
MSH6 negative
|
endometrial carcinoma
|
sensitive
|
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
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Crizotinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial (PROFILE 1001) that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate of 72% (38/53), with 6 complete responses and 32 partial responses, a median duration of response of 24.7 months, a median progression-free survival of 19.3 months, and a median overall survival of 51.4 months in patients with non-small cell lung cancer harboring ROS1 rearrangements as detected by an FDA-approved test (PMID: 30980071; NCT00585195).
|
detail...
detail...
30980071
|
NRAS wild-type
|
colorectal cancer
|
predicted - sensitive
|
Panitumumab
|
FDA approved - On Companion Diagnostic |
Actionable |
Vectibix (panitumumab) is FDA approved for metastatic colorectal patients that are NRAS wild-type, as detected by a companion diagnostic (FDA.gov).
|
detail...
detail...
|
CDK12 inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved progression-free survival (PFS, 5.8 vs 3.5 mo, HR=0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, including patients harboring CDK12 mutations (5.09 vs 2.20 mo) (PMID: 32343890; NCT02987543).
|
detail...
32343890
detail...
|
ATM inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment improved progression-free survival (7.4 vs 3.6 mo, HR=0.34, p<0.001), objective response rate (33%, 28/84 vs 2%, 1/43, OR=20.86, p<0.001), and median time to pain progression (HR=0.44, p=0.02) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in BRCA1/2 or ATM who progressed on hormone therapy (PMID: 32343890; NCT02987543).
|
detail...
32343890
detail...
|
ALK fusion
|
lung non-small cell carcinoma
|
sensitive
|
Alectinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in non-small cell lung cancer patients harboring ALK rearrangements (PMID: 28586279; NCT02075840).
|
detail...
28586279
detail...
|
BRAF V600K
|
melanoma
|
sensitive
|
Dabrafenib + Trametinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (COMBI-v) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved overall survival rate at 12 months (72% vs 65%, HR=0.69, p=0.005), median progression-free survival (11.4 vs 7.3 months, HR=0.56, p<0.001), and objective response rate (64% vs 51%, p<0.001) compared to Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (PMID: 25399551; NCT01597908).
|
detail...
25399551
detail...
|
ALK fusion
|
lung non-small cell carcinoma
|
sensitive
|
Ceritinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Zykadia (ceritinib) resulted in a blinded independent review committee (BIRC)-assessed objective response rate of 44% (72/163) and a duration of response of 7.1 months in ALK-rearranged non-small cell lung cancer patients (PMID: 25754348; NCT01283516).
|
detail...
detail...
25754348
|
FLT3 I836X
|
acute myeloid leukemia
|
sensitive
|
Gilteritinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (ADMIRAL) that supported FDA approval, Xospata (gilteritinib) treatment resulted in complete remission (CR) or CR with partial hematologic recovery in 21% (29/138) of patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD), D835, or I836 mutation (FDA.gov; NCT02421939).
|
detail...
detail...
|
IDH1 R132L
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 28.6% (8/28), CR with partial hematological recovery (CRh) in 14.3% (4/28) of patients age 75 or older with untreated acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a median treatment duration of 4.3 months (PMID: 29860938; NCT02074839).
|
29860938
detail...
detail...
|
BRAF V600E
|
melanoma
|
sensitive
|
Trametinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K-positive metastatic melanoma (PMID: 22663011; NCT01245062).
|
22663011
detail...
detail...
|
RAD51B inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved progression-free survival (PFS, 5.8 vs 3.5 mo, HR=0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, including patients harboring RAD51B mutations (10.89 vs 1.77 mo) (PMID: 32343890; NCT02987543).
|
detail...
detail...
32343890
|
BRAF V600E/K
|
melanoma
|
sensitive
|
Dabrafenib + Trametinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (COMBI-v) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved overall survival rate at 12 months (72% vs 65%, HR=0.69, p=0.005), median progression-free survival (11.4 vs 7.3 months, HR=0.56, p<0.001), and objective response rate (64% vs 51%, p<0.001) compared to Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (PMID: 25399551; NCT01597908).
|
detail...
detail...
25399551
|
FGFR3 S249C
|
transitional cell carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3 S249C is included in the companion diagnostic (PMID: 31340094; NCT02365597).
|
detail...
31340094
detail...
|
BRAF V600E/K
|
melanoma
|
sensitive
|
Binimetinib + Encorafenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) resulted in a median overall survival (OS) of 33.6 months, a 1-year OS rate of 77.5%, and a 2-year OS rate of 57.7% in patients with advanced melanoma harboring BRAF V600E/K mutations compared to a median OS of 16.9 months and 1- and 2-year OS rates of 63.1% and 43.2%, respectively, in the Zelboraf (vemurafenib) treated group (PMID: 30219628; NCT01909453).
|
detail...
detail...
detail...
30219628
|
IDH1 R132H
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 28.6% (8/28), CR with partial hematological recovery (CRh) in 14.3% (4/28) of patients age 75 or older with untreated acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a median treatment duration of 4.3 months (PMID: 29860938; NCT02074839).
|
29860938
detail...
detail...
|
ALK rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Crizotinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140).
|
detail...
25470694
detail...
|
FLT3 I836X
|
acute myeloid leukemia
|
sensitive
|
Cytarabine + Daunorubicin + Midostaurin
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial that supported FDA approval, treatment with Rydapt (midostaurin), combined with Cytosar-U (cytarabine) and Daunorubicin, improved overall survival (74.7 mo vs 25.6 mo) in patients with FLT3-mutant (D835X and I836X) or FLT3-ITD (exon 14 insertions) acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114).
|
detail...
detail...
28644114
|
FGFR2 mutant
|
transitional cell carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (PMID: 31340094; NCT02365597).
|
detail...
31340094
detail...
|
MLH1 negative
|
endometrial cancer
|
sensitive
|
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...
|
IDH2 R172S
|
acute myeloid leukemia
|
sensitive
|
Enasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172S is on the companion diagnostic.
|
28588020
detail...
detail...
|
ALK fusion
|
lung non-small cell carcinoma
|
sensitive
|
Crizotinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140).
|
25470694
detail...
detail...
|
FGFR3 R248C
|
transitional cell carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3 R248C is included in the companion diagnostic (PMID: 31340094; NCT02365597).
|
31340094
detail...
detail...
|
FGFR3 mutant
|
bladder urothelial carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (PMID: 31340094; NCT02365597).
|
detail...
31340094
detail...
|
BRAF V600E
|
melanoma
|
sensitive
|
Cobimetinib + Vemurafenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (coBRIM) that supported FDA approval, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf (vemurafenib) plus placebo, among patients with BRAF V600-mutated metastatic melanoma, and BRAF V600E and BRAF V600K are on the companion diagnostic (PMID: 27480103; NCT01689519).
|
27480103
detail...
detail...
|
FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Gilteritinib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase III trial (ADMIRAL) that supported FDA approval, Xospata (gilteritinib) treatment resulted in complete remission (CR) or CR with partial hematologic recovery in 21% (29/138) of patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD), D835, or I836 mutation (FDA.gov; NCT02421939).
|
detail...
detail...
|
IDH1 mutant
|
cholangiocarcinoma
|
sensitive
|
Ivosidenib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase III (ClarIDHy) trial that supported FDA approval, Tibsovo (ivosidenib) treatment significantly improved median progression-free survival (2.7 vs 1.4 mo, HR=0.37, p<0.001) and prolonged median overall survival (10.8 vs 9.7 mo, HR=0.69, p=0.06) compared to placebo in patients with advanced cholangiocarcinoma harboring IDH1 mutations including R132C/H/L/G/S, resulted in favorable objective response rate (2%, 3/124 vs 0%, 0/61) and stable disease rate (51% vs 28%) (PMID: 32416072; NCT02989857).
|
detail...
detail...
32416072
|
BRAF V600K
|
melanoma
|
sensitive
|
Binimetinib + Encorafenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) demonstrated improved tolerability profile and efficacy, resulted in a progression-free survival of 14.9 months in patients with advanced melanoma harboring BRAF V600E/K mutations, comparing to 7.3 months in the Zelboraf (vemurafenib) group (HR=0.54, p<0.0001) (PMID: 29573941; NCT01909453) and both BRAF V600E and BRAF V600K are on the companion diagnostic.
|
29573941
detail...
detail...
detail...
|
IDH1 R132H
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 21.6% (27/125), CR with partial hematological recovery (CRh) in 8.8% (11/125), and overall response (OR) in 41.6% (52/125) of patients with relapsed or refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test (PMID: 29860938; NCT02074839).
|
29860938
detail...
detail...
|
FGFR3 - TACC3
|
bladder urothelial carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3-TACC3 v1 and v3 fusions are included in the companion diagnostic (PMID: 31340094; NCT02365597).
|
detail...
31340094
detail...
|
FLT3 D835X
|
acute myeloid leukemia
|
sensitive
|
Cytarabine + Daunorubicin + Midostaurin
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial that supported FDA approval, treatment with Rydapt (midostaurin), combined with Cytosar-U (cytarabine) and Daunorubicin, improved overall survival (74.7 mo vs 25.6 mo) in patients with FLT3-mutant (D835X and I836X) or FLT3-ITD (exon 14 insertions) acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114).
|
detail...
28644114
detail...
|
MSH6 negative
|
Advanced Solid Tumor
|
predicted - sensitive
|
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...
|
IDH2 R172K
|
acute myeloid leukemia
|
sensitive
|
Enasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172K is on the companion diagnostic.
|
detail...
detail...
28588020
|
IDH2 R140L
|
acute myeloid leukemia
|
sensitive
|
Enasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R140L is on the companion diagnostic.
|
detail...
detail...
28588020
|
IDH2 mutant
|
acute myeloid leukemia
|
sensitive
|
Enasidenib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (R140Q/L/G/W, R172K/M/G/S/W) (PMID: 28588020; NCT01915498).
|
28588020
detail...
detail...
|
FLT3 D835X
|
acute myeloid leukemia
|
sensitive
|
Gilteritinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (ADMIRAL) that supported FDA approval, Xospata (gilteritinib) treatment resulted in complete remission (CR) or CR with partial hematologic recovery in 21% (29/138) of patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD), D835, or I836 mutation (FDA.gov; NCT02421939).
|
detail...
detail...
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FGFR3 Y373C
|
bladder urothelial carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3 Y373C is included in the companion diagnostic (PMID: 31340094; NCT02365597).
|
detail...
31340094
detail...
|
RAD51D inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved progression-free survival (PFS, 5.8 vs 3.5 mo, HR=0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, including patients harboring RAD51D mutations (PMID: 32343890; NCT02987543).
|
detail...
detail...
32343890
|
IDH1 R132L
|
cholangiocarcinoma
|
predicted - sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III (ClarIDHy) trial that supported FDA approval, Tibsovo (ivosidenib) treatment significantly improved median progression-free survival (2.7 vs 1.4 mo, HR=0.37, p<0.001) and prolonged median overall survival (10.8 vs 9.7 mo, HR=0.69, p=0.06) compared to placebo in patients with advanced cholangiocarcinoma harboring IDH1 mutations including R132C/H/L/G/S, resulted in favorable objective response rate (2%, 3/124 vs 0%, 0/61) and stable disease rate (51% vs 28%) (PMID: 32416072; NCT02989857).
|
detail...
32416072
detail...
|
FGFR3 Y373C
|
transitional cell carcinoma
|
sensitive
|
Erdafitinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3 Y373C is included in the companion diagnostic (PMID: 31340094; NCT02365597).
|
detail...
31340094
detail...
|
IDH2 R172M
|
acute myeloid leukemia
|
sensitive
|
Enasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172M is on the companion diagnostic.
|
28588020
detail...
detail...
|
FLT3 exon 14 ins
|
acute myeloid leukemia
|
sensitive
|
Gilteritinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (ADMIRAL) that supported FDA approval, Xospata (gilteritinib) treatment resulted in complete remission (CR) or CR with partial hematologic recovery in 21% (29/138) of patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD; exon 14 insertion), D835, or I836 mutation (FDA.gov; NCT02421939).
|
detail...
detail...
|
IDH1 R132C
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 28.6% (8/28), CR with partial hematological recovery (CRh) in 14.3% (4/28) of patients age 75 or older with untreated acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a median treatment duration of 4.3 months (PMID: 29860938; NCT02074839).
|
detail...
29860938
detail...
|
ALK fusion
|
lung non-small cell carcinoma
|
sensitive
|
Brigatinib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501).
|
detail...
detail...
detail...
|
BRAF V600E/K
|
melanoma
|
sensitive
|
Dabrafenib + Trametinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (COMBI-AD) that supported FDA approval, adjuvant treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved estimated 3-year relapse-free survival rate (58% vs 39%, HR=0.47, P<0.001) and 3-year overall survival rate (86% vs 77%, HR=0.57; 95% CI, 0.42 to 0.79, P=0.0006) compared to placebo in stage III melanoma patients harboring BRAF V600E or V600K mutations (PMID: 28891408; NCT01682083).
|
detail...
28891408
detail...
|
ALK rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Lorlatinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (Study B7461006) that supported FDA approval, Lorbrena (lorlatinib) treatment significantly improved 12-month progression-free survival rate (78% vs 39%, HR 0.28, p<0.001) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer who had no prior systemic therapy, objective response rate was 82% (57/69) with 71% achieved complete intracranial response in patients with brain metastasis (PMID: 33207094; NCT03052608).
|
33207094
detail...
detail...
|
FGFR2 fusion
|
cholangiocarcinoma
|
sensitive
|
Infigratinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial that supported FDA approval, Truseltiq (infigratinib) treatment demonstrated manageable toxicity, resulted in an objective response rate of 23.1% (25/108, 1 complete response, 24 partial responses) in patients with previously treated advanced cholangiocarcinoma harboring an FGFR2 fusion or rearrangement, with a median duration of response of 5.0 months and a median progression-free survival of 7.3 months (J Clin Oncol 39, no. 3_suppl (January 20, 2021) 265-265; NCT02150967).
|
detail...
detail...
detail...
|
ALK rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Ceritinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Zykadia (ceritinib) resulted in a blinded independent review committee (BIRC)-assessed objective response rate of 44% (72/163) and a duration of response of 7.1 months in ALK-rearranged non-small cell lung cancer patients (PMID: 25754348; NCT01283516).
|
25754348
detail...
detail...
|
IDH1 R132H
|
cholangiocarcinoma
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III (ClarIDHy) trial that supported FDA approval, Tibsovo (ivosidenib) treatment significantly improved median progression-free survival (2.7 vs 1.4 mo, HR=0.37, p<0.001) and prolonged median overall survival (10.8 vs 9.7 mo, HR=0.69, p=0.06) compared to placebo in patients with advanced cholangiocarcinoma harboring IDH1 mutations including R132C/H/L/G/S, resulted in favorable objective response rate (2%, 3/124 vs 0%, 0/61) and stable disease rate (51% vs 28%) (PMID: 32416072; NCT02989857).
|
detail...
32416072
detail...
|
MSH6 negative
|
endometrial cancer
|
sensitive
|
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...
|
IDH1 R132C
|
cholangiocarcinoma
|
predicted - sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III (ClarIDHy) trial that supported FDA approval, Tibsovo (ivosidenib) treatment significantly improved median progression-free survival (2.7 vs 1.4 mo, HR=0.37, p<0.001) and prolonged median overall survival (10.8 vs 9.7 mo, HR=0.69, p=0.06) compared to placebo in patients with advanced cholangiocarcinoma harboring IDH1 mutations including R132C/H/L/G/S, resulted in favorable objective response rate (2%, 3/124 vs 0%, 0/61) and stable disease rate (51% vs 28%) (PMID: 32416072; NCT02989857).
|
detail...
detail...
32416072
|
ALK rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Alectinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in non-small cell lung cancer patients harboring ALK rearrangement (PMID: 28586279; NCT02075840).
|
28586279
detail...
detail...
|
CHEK1 inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved progression-free survival (PFS, 5.8 vs 3.5 mo, HR=0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, including patients harboring CHEK1 mutations (PMID: 32343890; NCT02987543).
|
detail...
detail...
32343890
|
FGFR2 rearrange
|
cholangiocarcinoma
|
sensitive
|
Pemigatinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II (FIGHT-202) trial, Pemazyre (pemigatinib) treatment resulted in an objective response in 35.5% (38/107, 3 complete response, 35 partial response) of patients with advanced cholangiocarcinoma harboring FGFR2 fusions or rearrangements, with a disease control rate of 82% (88/107), median time-to-response of 2.7 months, and a median progression-free survival of 6.9 months (PMID: 32203698; NCT02924376).
|
detail...
32203698
detail...
|
IDH1 R132S
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 21.6% (27/125), CR with partial hematological recovery (CRh) in 8.8% (11/125), and overall response (OR) in 41.6% (52/125) of patients with relapsed or refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test (PMID: 29860938; NCT02074839).
|
detail...
29860938
detail...
|
ROS1 fusion
|
lung non-small cell carcinoma
|
sensitive
|
Crizotinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate of 72% (36/50), with 3 complete responses and 33 partial responses, a median duration of response of 17.6 months, and a median progression-free survival of 19.2 months in patients with non-small cell lung cancer harboring ROS1 rearrangements as detected by an FDA-approved test (PMID: 25264305; NCT00585195).
|
detail...
25264305
detail...
|