jack14 Posted May 16, 2020 Share Posted May 16, 2020 Biomarker Findings Microsatellite status -MS-Stable Tumor Mutational Burden - 9 Muts/Mb Genomic Findings For a complete list of the genes assayed, please refer to the Appendix. MET amplification CCND1 amplification SMARCB1 R374Q - subclonal† MTAP loss C11orf30 (EMSY) amplification CDKN2A/B loss DNMT3A R598* EPHB4 amplification - equivocal† FGF19 amplification FGF3 amplification FGF4 amplification HGF R424C KEL R192* TP53 splice site 375G>C 7 Disease relevant genes with no reportable alterations: ALK, BRAF, EGFR, ERBB2, KRAS, RET, ROS1 Link to comment Share on other sites More sharing options...
jack14 Posted May 16, 2020 Author Share Posted May 16, 2020 Microsatellite status - MS-Stable No therapies or clinical trials. Tumor Mutational Burden - 9 Muts/Mb No therapies or clinical trials. MET - amplification 10 Trials see p. 16 Crizotinib 2A Cabozantinib CCND1 - amplification 10 Trials see p. 14 none Abemaciclib Palbociclib Ribociclib SMARCB1 - R374Q - subclonal 10 Trials see p. 19 none Tazemetostat MTAP - loss 1 Trial see p. 18 What does this suggest? Can anyone decipher for me? Is it saying that the MET amplification is the only mutation for which there might be a drug that could potentially target it? Link to comment Share on other sites More sharing options...
BridgetO Posted May 16, 2020 Share Posted May 16, 2020 I would ask whatever doc ordered this test for a line by line interpretation. Do you have the other pages it refers to? If not, I would ask for them. To me, this suggest their may be clinical trials for some of these biomarkers. Link to comment Share on other sites More sharing options...
jack14 Posted May 16, 2020 Author Share Posted May 16, 2020 Yes, I do have the rest of the report. and there are several trials in place with a couple in my State. But I have just began a Keytrude course and perhaps one of the trials might end up producing something down the road? Thanks Bridget. NCT02414139 PHASE 2 Clinical Study of Oral cMET Inhibitor INC280 in adult Patients With EGFR Wild-type Advanced Nonsmall Cell Lung Cancer TARGETS MET LOCATIONS: North Carolina, South Carolina, Virginia, District of Columbia, Georgia, Pennsylvania, Tennessee, Michigan NCT03170960 PHASE 1/2 Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors TARGETS PD-L1, MET, RET, ROS1, VEGFRs LOCATIONS: Virginia, District of Columbia, Georgia, Kentucky, Ohio, Pennsylvania, Florida, New Jersey NCT02099058 PHASE 1 A Phase 1/1b Study With ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Cancer Tumors TARGETS MET, EGFR, PD-1 LOCATIONS: North Carolina, Virginia, Tennessee, Michigan, Illinois, Massachusetts, Texas, Colorado, California NCT04173338 PHASE 1 Cabozantinib With Pemetrexed in Advanced Non-small Cell Lung Cancer, Urothelial Cancer and Malignant Mesothelioma TARGETS MET, RET, ROS1, VEGFRs LOCATIONS: Georgia NCT03906071 PHASE 3 Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous NSCLC TARGETS PD-1, AXL, DDR2, FLT3, KIT, MET, PDGFRA, RET, TRKA, TRKB, VEGFRs LOCATIONS: Virginia, Maryland, Georgia, Kentucky, Ohio, Alabama, Tennessee NCT03539536 PHASE 2 Study of Telisotuzumab Vedotin (ABBV-399) in Subjects With Previously Treated c-Met+ Non-Small Cell Lung Cancer TARGETS MET LOCATIONS: Virginia, Kentucky, Tennessee, Michigan, Toronto (Canada), Illinois, Alabama NCT02609776 PHASE 1 A Dose Escalation Study of JNJ-61186372 in Participants With Advanced Non-Small Cell Lung Cancer TARGETS MET, EGFR Link to comment Share on other sites More sharing options...
Rower Michelle Posted May 19, 2020 Share Posted May 19, 2020 Jack Would you be eligible for the newly approved targeted therapy for MET? https://www.curetoday.com/articles/fda-approves-tabrecta-the-first-targeted-drug-for-patients-with-nonsmall-cell-lung-cancer-and-met-exon-14 It would appear as if MET would be the target. Right now as you are such quick study there are about 8 targeted mutations which defines the first course of treatment. Michelle Link to comment Share on other sites More sharing options...
LUNGevityKristin Posted May 19, 2020 Share Posted May 19, 2020 Jack, Here is more information on clinical trials and a resource for a clinical trial navigator if you would like to talk with someone who has been through the process before. https://lungevity.org/for-patients-caregivers/lung-cancer-101/find-clinical-trial Link to comment Share on other sites More sharing options...
jack14 Posted May 19, 2020 Author Share Posted May 19, 2020 Thanks Michelle and Kristin. I am not sure about this. I have the report in hand, as it came today via FedX. It is a hard copy of the one I got digitally last week. I don't see any reference to the exon 14 though.... Just the MET amplification Link to comment Share on other sites More sharing options...
Deb W Posted June 5, 2020 Share Posted June 5, 2020 Hi Jack, I just found out that I had MET amplification last week. I'm not certain about the exon 14 part either, but I'm going to discuss it with my oncologist. This drug is being considered for me. I'll know more when I meet w/him on Tuesday. https://www.emdgroup.com/en/news/tepotinib-25-03-2020.html Link to comment Share on other sites More sharing options...
jack14 Posted June 9, 2020 Author Share Posted June 9, 2020 Hi Deb Yes that is good information and answered my question. Here is the excerpt that defines what I was concerned about: "Tepotinib is an oral MET inhibitor that is designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, including both METex14 skipping alterations and MET amplifications, or MET protein overexpression." In other words, I have the "MET amplication" and not the "METex14", although thankfully, both are included. Have you been able to confirm this? Link to comment Share on other sites More sharing options...
jack14 Posted June 9, 2020 Author Share Posted June 9, 2020 Hi Deb But this is just a "possible" remedy which the FDA has allowed to be tried here in the USA for those who have not been able to get a NED through other treatment. As I understand it.... Link to comment Share on other sites More sharing options...
Deb W Posted June 9, 2020 Share Posted June 9, 2020 Hi Jack, That would explain another reason why he wants me to finish this treatment and see if it works. There might be other reasons that he's not sharing. He was very excited to have learned that I have MET which would give me another option should this treatment not work for me. So, today I had my second chemo treatment using Keytruda , Alimta and Carboplatin. My new oncologist tweaked the dose as I had a hard time with nausea lasting a long time with my first go round. I wrote a side effect journal and I'm glad I did so I can compare. So far, so good today. I'm sure the IV steroids are helping a lot with energy. I learned today that I have the MET exon 14 skipping. I mentioned to the oncologist that I read that Keytruda doesn't seem to be effective for MET. He said that many of the articles on that topic are theoretical . Still, we will have a more in depth conversation later. My understanding is that when I have my scan in 3 weeks, if there is no change I will be put on the Tepo drug. Not sure how that's going to happen if it takes a month to get the drug. I trust this Oncologist and the team of doctors on the tumor board. You can find more info on it here: https://www.mycancergenome.org/content/drugs/#in_biomarkers=MET Exon 14 Skipping&in_diseases=Non-Small Cell Lung Carcinoma&drug_categories=Immunotherapies Link to comment Share on other sites More sharing options...
jack14 Posted June 10, 2020 Author Share Posted June 10, 2020 Hi Deb: I haven't heard that before, about MET and Keytruda. I hope we aren't adversaly effected. I was told that it is wise to use treatments sparingly so that you have something in the arsenal for later on down the road should a therapy stop working or become intolerable. That is an interesting link too. I don't have much to input though as far as mutations, cept the MET amplication, assuming I am reading things correctly. I hope that we are both NED soon. That's what I am paying for! Stay safe and we are going to beat this. Jack Link to comment Share on other sites More sharing options...
Deb W Posted June 11, 2020 Share Posted June 11, 2020 Hi Jack, I understand the concern. Right now they want to see if these drugs work and I feel certain they have carefully evaluated my case and determined this is the route for me. It's like night and day when you know your oncologist is diligent and has a genuine interest in you as a human being. My first oncologist had the MET information right in front of him and missed it ...that is why I was given chemo. Now we'll see after the second round results how we'll proceed. It seems to me that all tumors should be sent for biomarker testing - then we know from the get go. The answer I was given as to why it wasn't done back in March is that it was stage 1B and all margins were clear with no lymph node involvement and no further treatment needed except follow-up scans....well, 13 months later it's Stage IV. I feel optimistic, I like my doctor's thinking around this as he said the goal is remission. That sounds like a good goal to me. This is a fabulous site with very knowledgeable people, and I'm so thankful I found them. Best, Deb Link to comment Share on other sites More sharing options...
MarieE Posted June 11, 2020 Share Posted June 11, 2020 https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-treat-aggressive-form-lung-cancer We just had a consult with my husband's oncologist and he is ordering this drug for his treatment. On my husband's NGS report it notes the MET E1009G alteration at 1.2% cfDNA or amplification and notes, "In this report, the MET E1009G variant is a MET exon 14 skipping alteration." Link to comment Share on other sites More sharing options...
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