CA-3275619-A1 - USE OF FGFR MUTANT GENE PANELS IN IDENTIFYING CANCER PATIENTS THAT WILL BE RESPONSIVE TO TREATMENT WITH AN FGFR INHIBITOR

CA3275619A1CA 3275619 A1CA3275619 A1CA 3275619A1CA-3275619-A1

Inventors

Jayaprakash Karkera
Suso Jesus PLATERO

Assignees

JANSSEN PHARMACEUTICA NV

Dates

Publication Date: 20260302
Application Date: 20150918
Priority Date: 20140926

Claims (1)

<pat:Claims com:id="claims"> <pat:Claim com:id="CLM-00001"> <pat:ClaimNumber>1</pat:ClaimNumber> <pat:ClaimText>1. Use of a fibroblast growth factor receptor (FGFR) inhibitor for the treatment of cancer in a patient when one or more FGFR mutant genes from a FGFR mutant gene panel is present in a biological sample from the patient evaluated for the presence of the one or more FGFR mutant genes, wherein the one or more FGFR mutant genes from the FGFR mutant gene panel comprises FGFR3 Y373C, and wherein the FGFR inhibitor comprises a compound having the structure of Formula (I), [Image disponible dans le document PDF, Image available in the PDF document] a N-oxide thereof, a pharmaceutically acceptable salt thereof, or a solvate thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00002"> <pat:ClaimNumber>2</pat:ClaimNumber> <pat:ClaimText>2. The use of claim 1, wherein the FGFR inhibitor is the compound of Formula (I) [Image disponible dans le document PDF, Image available in the PDF document] </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00003"> <pat:ClaimNumber>3</pat:ClaimNumber> <pat:ClaimText>3. The use of claim 1 or 2, wherein the one or more FGFR mutant genes further comprise FGFR3 R248C or FGFR3 G370C, or any combination thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00004"> <pat:ClaimNumber>4</pat:ClaimNumber> <pat:ClaimText>4. The use of claim 1 or 2, wherein the cancer is bladder cancer and the one or more FGFR mutant genes further comprise FGFR3:TACC3 v1, FGFR3:TACC3 v3, FGFR3:BAIAP2L1, FGFR2:BICC1, FGFR2:AFF3, FGFR2:CASP7, FGFR3 R248C, or FGFR3 G370C, or any combination thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00005"> <pat:ClaimNumber>5</pat:ClaimNumber> <pat:ClaimText>5. The use of claim 1 or 2, wherein the cancer is metastatic bladder cancer and the one or more FGFR mutant genes further comprise FGFR3:TACC3 v1, FGFR3:TACC3 v3, FGFR3:BAIAP2L1, FGFR2:BICC1, FGFR2:AFF3, FGFR2:CASP7, FGFR3 R248C, or FGFR3 G370C, or any combination thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00006"> <pat:ClaimNumber>6</pat:ClaimNumber> <pat:ClaimText>6. The use of claim 4 or 5, wherein the one or more FGFR mutant genes further comprise FGFR3:TACC3 v1 or FGFR3:TACC3 v3. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00007"> <pat:ClaimNumber>7</pat:ClaimNumber> <pat:ClaimText>7. The use of any one of claims 4-6, wherein the one or more FGFR mutant genes further comprise FGFR3:BAIAP2L1. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00008"> <pat:ClaimNumber>8</pat:ClaimNumber> <pat:ClaimText>8. The use of any one of claims 4-7, wherein the one or more FGFR mutant genes further comprise FGFR2:BICC1 </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00009"> <pat:ClaimNumber>9</pat:ClaimNumber> <pat:ClaimText>9. The use of any one of claims 4-8, wherein the one or more FGFR mutant genes further comprise FGFR2:CASP7. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00010"> <pat:ClaimNumber>10</pat:ClaimNumber> <pat:ClaimText>10. The use of any one of claims 4-9, wherein the one or more FGFR mutant genes further comprise FGFR3 R248C. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00011"> <pat:ClaimNumber>11</pat:ClaimNumber> <pat:ClaimText>11. The use of any one of claims 4-10, wherein the one or more FGFR mutant genes further comprise FGFR3 G370C. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00012"> <pat:ClaimNumber>12</pat:ClaimNumber> <pat:ClaimText>12. The use of claim 1 or 2, wherein the cancer is ovarian cancer and the one or more FGFR mutant genes further comprise FGFR3:TACC3 v1, FGFR3:TACC3 v3, FGFR3:BAIAP2L1, FGFR2:BICC1, FGFR2:AFF3, FGFR2:CASP7, FGFR3 R248C, or FGFR3 G370Cor any combination thereof; or wherein the cancer is head and neck cancer and the one or more FGFR mutant genes further comprise FGFR3:BAIAP2Ll, FGFR2:CASP7, FGFR3 R248C, or FGFR3 G370C, or any combination thereof; or wherein the cancer is esophageal cancer and the one or more FGFR mutant genes further comprise FGFR3:TACC3 v1, FGFR3:TACC3 v3, FGFR2:BICC1, FGFR2:CASP7, FGFR3 R248C, or FGFR3 G370C, or any combination thereof; or wherein the cancer is non-small-cell lung adenocarcinoma and the one or more FGFR mutant genes further comprise FGFR3:TACC3 v1, FGFR3:TACC3 v3, FGFR3:TACC3 Intron, FGFR3:BAIAP2L1, FGFR2:AFF3, FGFR2:CASP7, FGFR3 R248C, or FGFR3 G370C, or any combination thereof; or wherein the cancer is non-small cell lung squamous cell carcinoma and the one or more FGFR mutant genes further comprise FGFR3:TACC3 v1, FGFR3:TACC3 v3, FGFR3:BAIAP2L1, FGFR2:BICC1, FGFR2:AFF3, FGFR2:CASP7, FGFR2:CCDC6, FGFR3 R248C, or FGFR3 G370C, or any combination thereof; or wherein the cancer is hepatocellular carcinoma and the one or more FGFR mutant genes further comprise FGFR3:TACC3 v1, FGFR3:TACC3 v3, FGFR3:TACC3 Intron, FGFR3:BAIAP2L1, FGFR2:BICC1, FGFR2:AFF3, FGFR2:CASP7, FGFR2:CCDC6, FGFR2:OFD1, FGFR3 R248C, or FGFR3 G370C, or any combination thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00013"> <pat:ClaimNumber>13</pat:ClaimNumber> <pat:ClaimText>13. The use of any one of claims 1-12, wherein the evaluating comprises amplifying a cDNA with a pair of primers that amplify the one or more FGFR mutant genes from the FGFR mutant gene panel. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00014"> <pat:ClaimNumber>14</pat:ClaimNumber> <pat:ClaimText>14. The use of claim 13, wherein the one or more FGFR mutant genes and pair of primers are FGFR3 Y373C and primers having the sequences of SEQ ID NO:29 and SEQ ID NO:30 or SEQ ID NO:37 and SEQ ID NO:38, and optionally: FGFR3:TACC3 v1 and primers having the sequences of SEQ ID NO:5 and SEQ ID NO:6; FGFR3:TACC3 v3 and primers having the sequences of SEQ ID NO:7 and SEQ ID NO:8; FGFR3:TACC3 Intron and primers having the sequences of SEQ ID NO:9 and SEQ ID NO:10; FGFR3:BAIAP2L 1 and primers having the sequences of SEQ ID NO:11 and SEQ ID NO:12; FGFR2:BICC 1 and primers having the sequences of SEQ ID NO:13 and SEQ ID NO:14; FGFR2:AFF3 and primers having the sequences of SEQ ID NO:15 and SEQ ID NO:16; FGFR2:CASP7 and primers having the sequences of SEQ ID NO:17 and SEQ ID NO:18; FGFR2:CCDC6 and primers having the sequences of SEQ ID NO:19 and SEQ ID NO:20; FGFR2:OFD1 and primers having the sequences of SEQ ID NO:21 and SEQ ID NO:22; FGFR3 R248C and primers having the sequences of SEQ ID NO:23 and SEQ ID NO:24 or SEQ ID NO:31 and SEQ ID NO:32; FGFR3 G370C and primers having the sequences of SEQ ID NO:27 and SEQ ID NO:28 or SEQ ID NO:35 and SEQ ID NO:36; or any combination thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00015"> <pat:ClaimNumber>15</pat:ClaimNumber> <pat:ClaimText>15. The use of claim 13 or 14, wherein the evaluating comprises: isolating an RNA from the biological sample and synthesizing the cDNA from the isolated RNA. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00016"> <pat:ClaimNumber>16</pat:ClaimNumber> <pat:ClaimText>16. The use of claim 15, further comprising pre-amplifying the cDNA prior to amplifying the one or more FGFR mutant genes from the FGFR mutant gene panel. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00017"> <pat:ClaimNumber>17</pat:ClaimNumber> <pat:ClaimText>17. The use of any one of claims 13-16, wherein the amplifying step comprises performing a real-time PCR. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00018"> <pat:ClaimNumber>18</pat:ClaimNumber> <pat:ClaimText>18. The use of claim 17, wherein the real-time PCR is performed with one or more probes comprising SEQ ID NO:55 and optionally SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, and/or SEQ ID NO:54. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00019"> <pat:ClaimNumber>19</pat:ClaimNumber> <pat:ClaimText>19. The use of claim 17 or 18, wherein the real-time PCR is performed with one or more 3' blocking oligonucleotides comprising SEQ ID NO:42, and optionally SEQ ID NO:39 and/or SEQ ID NO:41. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00020"> <pat:ClaimNumber>20</pat:ClaimNumber> <pat:ClaimText>20. The use of any one of claims 13-19, comprising sequencing the amplified cDNA. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00021"> <pat:ClaimNumber>21</pat:ClaimNumber> <pat:ClaimText>21. The use of any one of claims 1-20, wherein the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample, FFPET (Formalin-Fixed Paraffin-Embedded Tissue), or any combination thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00022"> <pat:ClaimNumber>22</pat:ClaimNumber> <pat:ClaimText>22. The use of claim 21, wherein the biological sample is a solid tumor sample. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00023"> <pat:ClaimNumber>23</pat:ClaimNumber> <pat:ClaimText>23. A kit for identifying the presence of one or more FGFR mutant genes in a biological sample comprising: at least a pair of primers having the sequences of SEQ ID NO:29 and SEQ ID NO:30 or SEQ ID NO:37 and SEQ ID NO:38, and optionally pairs of primers having the sequences of SEQ ID NO:5 and SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8, SEQ ID NO:9 and SEQ ID NO:10, SEQ ID NO:11 and SEQ ID NO:12, SEQ ID NO:13 and SEQ ID NO:14, SEQ ID NO:15 and SEQ ID NO:16, SEQ ID NO:17 and SEQ ID NO:18, SEQ ID NO:19 and SEQ ID NO:20, SEQ ID NO:21 and SEQ ID NO:22, SEQ ID NO:23 and SEQ ID NO:24, SEQ ID NO:27 and SEQ ID NO:28, , SEQ ID NO:31 and SEQ ID NO:32, SEQ ID NO:35 and SEQ ID NO:36, or any combination thereof; and instructions for performing an assay to detect at least FGFR3 Y373C. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00024"> <pat:ClaimNumber>24</pat:ClaimNumber> <pat:ClaimText>24. The kit of claim 23, further comprising one or more probes, one or more 3' blocking oligonucleotides, or both. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00025"> <pat:ClaimNumber>25</pat:ClaimNumber> <pat:ClaimText>25. The kit of claim 23, wherein a) the pair of primers have the sequences SEQ ID NO:29 and SEQ ID NO:30 and the probe has the sequence of SEQ ID NO:55; or b) the pair of primers have the sequences SEQ ID NO:37 and SEQ ID NO:38, and the probe has the sequence of SEQ ID NO:55; and optionally: a) the pair of primers have the sequences SEQ ID NO:5 and SEQ ID NO:6 and the probe has the sequence of SEQ ID NO:43; b) the pair of primers have the sequences SEQ ID NO:7 and SEQ ID NO:8 and the probe has the sequence of SEQ ID NO:44; c) the pair of primers have the sequences SEQ ID NO:9 and SEQ ID NO:10 and the probe has the sequence of SEQ ID NO:46; d) the pair of primers have the sequences SEQ ID NO:11 and SEQ ID NO:12 and the probe has the sequence of SEQ ID NO:47; e) the pair of primers have the sequences SEQ ID NO:13 and SEQ ID NO:14 and the probe has the sequence of SEQ ID NO:45; f) the pair of primers have the sequences SEQ ID NO:15 and SEQ ID NO:16 and the probe has the sequence of SEQ ID NO:48; g) the pair of primers have the sequences SEQ ID NO:17 and SEQ ID NO:18 and the probe has the sequence of SEQ ID NO:49; h) the pair of primers have the sequences SEQ ID NO:19 and SEQ ID NO:20 and the probe has the sequence of SEQ ID NO:50; i) the pair of primers have the sequences SEQ ID NO:21 and SEQ ID NO:22 and the probe has the sequence of SEQ ID NO:51; j) the pair of primers have the sequences SEQ ID NO:23 and SEQ ID NO:24 and the probe has the sequence of SEQ ID NO:52; k) the pair of primers have the sequences SEQ ID NO:27 and SEQ ID NO:28 and the probe has the sequence of SEQ ID NO:54; 1) the pair of primers have the sequences SEQ ID NO:31 and SEQ ID NO:32, the probe has the sequence of SEQ ID NO:52, and the 3' blocking oligonucleotide has the sequence of SEQ ID NO:39; m) the pair of primers have the sequences SEQ ID NO:35 and SEQ ID NO:36, the probe has the sequence of SEQ ID NO:54, and the 3' blocking oligonucleotide has the sequence of SEQ ID NO:41; or n) any combination thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00026"> <pat:ClaimNumber>26</pat:ClaimNumber> <pat:ClaimText>26. A primer having the sequence of SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:37, or SEQ ID NO:38, or a combination thereof, optionally in combination with a primer having the nucleic acid sequence of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:36 or any combination thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00027"> <pat:ClaimNumber>27</pat:ClaimNumber> <pat:ClaimText>27. A set of primers having the sequences of SEQ ID NO:29 and SEQ ID NO:30 and/or SEQ ID NO:37 and SEQ ID NO:38, optionally in combination with primers having the sequences of SEQ ID NO:5 and SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8, SEQ ID NO:9 and SEQ ID NO:10, SEQ ID NO:11 and SEQ ID NO:12, SEQ ID NO:13 and SEQ ID NO:14, SEQ ID NO:15 and SEQ ID NO:16, SEQ ID NO:17 and SEQ ID NO:18, SEQ ID NO:19 and SEQ ID NO:20, SEQ ID NO:21 and SEQ ID NO:22, SEQ ID NO:23 and SEQ ID NO:24, SEQ ID NO:27 and SEQ ID NO:28, SEQ ID NO:31 and SEQ ID NO:32, SEQ ID NO:35 and SEQ ID NO:36, or any combination thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00028"> <pat:ClaimNumber>28</pat:ClaimNumber> <pat:ClaimText>28. An oligonucleotide probe having the sequence of SEQ ID NO:55, optionally in combination with an oligonucleotide probe having the sequence of any one of SEQ ID NOs: 43-52, or 54, or any combination thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00029"> <pat:ClaimNumber>29</pat:ClaimNumber> <pat:ClaimText>29. An oligonucleotide having the sequence of SEQ ID NO: 55 in combination with an oligonucleotide having the sequence of SEQ ID NO:42, optionally in combination with an oligonucleotide having the sequence of any one of SEQ ID NOs: 39 or 41, or any combination thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00030"> <pat:ClaimNumber>30</pat:ClaimNumber> <pat:ClaimText>30. A method of identifying a cancer patient who will be responsive to treatment with a fibroblast growth factor receptor (FGFR) inhibitor comprising: evaluating a biological sample from the patient for the presence of one or more FGFR mutant genes from a FGFR mutant gene panel, wherein the one or more FGFR mutant genes from the FGFR mutant gene panel comprises FGFR3 Y373C, and wherein said evaluating comprises amplifying a cDNA with a pair of primers that amplify the one or more FGFR mutant genes from the FGFR mutant gene panel; and determining whether the one or more FGFR mutant genes from the FGFR mutant gene panel are present in the sample, wherein the presence of the one or more FGFR mutant genes indicates that the patient will be responsive to treatment with the FGFR inhibitor, and wherein the FGFR inhibitor comprises a compound having the structure of Formula (I), [Image disponible dans le document PDF, Image available in the PDF document] a N-oxide thereof, a pharmaceutically acceptable salt thereof, or a solvate thereof. </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00031"> <pat:ClaimNumber>31</pat:ClaimNumber> <pat:ClaimText>31. Use of a fibroblast growth factor receptor (FGFR) inhibitor for the treatment of cancer in a patient when one or more FGFR mutant genes from a FGFR mutant gene panel is present in a biological sample from the patient evaluated for the presence of the one or more FGFR mutant genes, wherein the one or more FGFR mutant genes from the FGFR mutant gene panel comprises FGFR3-TACC3 v1, FGFR3:TACC3 v3, FGFR3:BAIAP2L1, FGFR2:BICC1, FGFR2:AFF3, FGFR2:CASP7, FGFR3 R248C, or FGFR3 G370C or any combination thereof, and wherein the FGFR inhibitor comprises a compound having the structure of Formula (I), [Image disponible dans le document PDF, Image available in the PDF document] (I), a N-oxide thereof, a pharmaceutically acceptable salt thereof, or a solvate thereof. </pat:ClaimText> </pat:Claim> </pat:Claims>

Description

USE OF FGFR MUTANT GENE PANELS IN IDENTIFYING CANCER PATIENTS THAT WILL BE RESPONSIVE TO TREATMENT WITH AN FGFR INHIBITOR SEQUENCE LISTING [0002] The instant application contains a Sequence Listing which has been submitted electronically in ASCII format. Said ASCII copy, created on August 6, 2015, is named 103693.000782_SL.txt and is 66,185 bytes insize. TECHNICAL FIELD [0003] Provided herein are methods of identifying a cancer patient that will be responsive to treatment with a fibroblast growth factor receptor inhibitor and methods of treating the same. BACKGROUND [0004] The identification of genetic abnormalities can be useful in selecting the appropriate therapeutic(s) for cancer patients. This is also useful for cancer patients failing the main therapeutic option (front-line therapy) for that cancer type, particularly if there is no accepted standard of care for second and subsequent-line therapy. Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases involved in regulating cell survival, proliferation, migration and differentiation. FGFR alterations have been observed in some cancers. To date, there are no approved therapies that are efficacious in patients with FGFR alterations. SUMMARY [0005] Disclosed herein are methods of identifying a cancer patient that will be responsive to treatment with a fibroblast growth factor receptor (FGFR) inhibitor comprising: evaluating a biological sample from the patient for a FGFR mutant from a FGFR mutant gene panel, wherein the FGFR mutant is a FGFR fusion gene or a FGFR single nucleotide polymorphism, and wherein said evaluating comprises amplifying cDNA with a pair of primers that bind to and amplify one or more FGFR mutants from the FGFR mutant gene panel; and determining whether the one or more FGFR mutants from the gene panel are present in the sample, wherein the presence of the one or more FGFR mutants indicates that the patient will be responsive to treatment with the FGFR inhibitor. [0006] Also disclosed are methods of treating cancer in a patient comprising: evaluating a biological sample from the patient for the presence of one or more FGFR mutants from a FGFR mutant gene panel; and treating the patient with an FGFR inhibitor if one or more FGFR mutants are present in the sample. [0007] Kits and primers for identifying the presence of one or more FGFR mutant genes in a biological sample are further provided herein. BRIEF DESCRIPTION OF THE DRAWINGS [0008] The summary, as well as the following detailed description, is further understood when read in conjunction with the appended drawings. For the purpose of illustrating the disclosed methods, kits, and primers, there are shown in the drawings exemplary embodiments of the methods, kits, and primers; however, the methods, kits, and primers are not limited to the specific embodiments disclosed. In the drawings: [0009] FIG. 1 is an illustration of exemplary FGFR fusion genes, the presence of at least one of which indicates that a patient will be responsive to treatment with an FGFR inhibitor. Also illustrated (small arrows) are exemplary primer locations for amplifying the fusion genes. [0010] FIG. 2, comprising FIGS. 2A-2I, represents Sanger sequencing results from FFPET samples positive for: A) FGFR3:TACC3 v1; B) FGFR3:TACC3 v3; C) FGFR3:TACC3 Intron; D) FGFR3:BAIAP2L1; E) FGFR2:AFF3; F) FGFR2:BICC1; G) FGFR2:CASP7; H) FGFR2:CCDC6; and I) FGFR2:OFD1. [0011] FIG. 3 illustrates an exemplary strategy for SNP-specific qRT-PCR using a 3' didcoxy wild type (WT) blocker oligonucleotide. [0012] FIG. 4 illustrates an exemplary analytical validation strategy for detecting FGFR SNPs. Experiments were performed on engineered RK3E cell lines expressing the FGFR fusions and diluted into a wild type cell line harboring no FGFR3/FGFR2 fusions. [0013] FIG. 5, comprising FIGS. 5A-5D, illustrates SNP-specific PCR with dideoxy WT blocker for (a) G370C, (B) Y373C, (C) S249C, and (D) R248C. [0014] FIG. 6, comprising FIGS. 6A-6I, represents efficiency standard curves for the FGFR fusion gene assays: A) FGFR3:TACC3 v1; B) FGFR3:TACC3 v3; C) FGFR3:TACC3 Intron; D) FGFR3:BAIAP2L1; E) FGFR2:AFF3; F) FGFR2:BICC1; G) FGFR2:CASP7; H) FGFR2:CCDC6; and I) FGFR2:OFD1. [0015] FIG. 7 is an exemplary representation of FGFR fusion gene status in bladder (primary and metastatic), NSCLC (adenocarcinoma and squamous), ovarian, esophageal (primary and metastatic), head and neck (H&N; primary and metastatic), endometrial (metastatic), breast, and prostate cancer. [0016] FIG. 8 is an exemplary representation of FGFR fusion gene and mutation status in NSCLC adenocarcinoma and squamous cell carcinoma. [0017] FIG. 9, comprising FIGS. 9A-9D, represents exemplary results from phase I patient samples. Assays were performed using synthetic template assay control (ST), primers for GAPDH (quality control sample), or primers specific for: A) FGFR2:BICC1 fusions; B) FGFR3:TACC3 (exon 18:exon 1) fusions; C) FGFR2:CCDC6 fusions; o