Any drugs / clinical trials for KRAS mutation?

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Hi

My mom who is now stage IV NSCLC adenocarcinoma with mets in bone, brain and liver is just told that she has the KRAS mutation. But her doctor said there is no drugs and no clinical trials going on for this mutation.

Does anyone have any knowledge about this? Or can point me to any website that may contain this information? Thanks so much in advance.

Shelly

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Battle II at MDA Houston.

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I am sure CraiginPa will have much more information for you but I would give Dr. Alice Shaw at Mass General in Boston a call.
http://www.massgeneral.org/doctors/doctor.aspx?ID=17279

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clinicaltrials.gov. I just put in K-RAS and lung cancer and came up with several. You have to review the eligibilty and location to see if she's eligible. There are several completed, so skip over those. Is she on any treatment now? Take care, Judy
http://clinicaltrials.gov/ct2/results?term=K-RAS+and+lung+cancer

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Shelly,
I'm in almost the exact situation - my mom has stage IV NSCLC adenocarcinoma with mets in brain and liver (no bone, yet) and is also KRAS positive. Once we found out she has the KRAS mutation, i did a lot of research and found that there are no specific targeted therapies, but there are a lot of investigational drugs that appear promising for KRAS patients.

Here's a discussion on an archived CancerGRACE forum from earlier this year that discusses many of the options: http://cancergrace.org/forums/index.php?topic=6350.0. If you haven't been on CancerGrace yet, i HIGHLY recommend it! This patient community for NSCLC has been a tremendous resource http://cancergrace.org/.

And, to specifically answer your question, below are some of the drugs that researchers are looking at to treat NSCLC with KRAS:

Tivantinib (ARQ 197)
•c-Met Inhibitor
http://www.arqule.com/res/onc/

Ganetespib (STA-9090)
•Hsp90 Inhibitor
http://www.syntapharma.com/prdHsp90.aspx

Retaspimycin HCl (IPI-504)
•Hsp90 Inhibitor
http://www.infi.com/product-candidates-pipeline-ipi-504.asp

Selumetinib (AZD6244) - isn't looking as promising as others
•c-Met Inhibitor
http://www.arraybiopharma.com/Collaboration/AstraZenecaDeal.asp

Nexavar (sorafenib) - isn't looking as promising as others
http://www.nexavar-international.com/home/hcp_moa/index.php

GSK1120212 (JTP-74057)
•MEK Inhibitor

Seach www.clinicaltrials.org for trials with these drugs. I'd also possible check out the FDA’s Emergency Use Investigational New Drug Program for Oncology Drugs: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedand Approved/ApprovalApplications/InvestigationalNewDrugINDApplication/ucm10743 4.htm

Hope this helps and I relate to the situation you are in!

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Hi

I was just at City Of Hope in Duarte last week and they have a trial going on for KRAS...it's the AZD6244 alone or in combination with Tarceva. Good Luck

Mary

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Thank you all so much for your helpful insights!!

@MomFightsNSCLC - what a treasure trove of information you provided. This is exactly what i am looking for. Will look into each drug more in depth but this is a terrific starting point.

@Judy - thank you for the link. I looked at the sight and have contacted KRAS clinic trials for information. Very helpful.

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I think you've already been given very good answers and I can't add much, but . . .

FWIW, here's my list of "potential" (not necessarily promising) drugs or combos for KRAS that I've heard mentioned in news or research, although I haven't specifically been researching for KRAS so this isn't complete or necessarily the best list.

The most interesting one, claiming a 60% success rate among the small number KRAS patients in their early-phase trial, is ganetespib, as you can read at:
http://www.aacr.org/home/public--media/aacr-press-releases.aspx?d=2671
However, that's a 'marketing' release, so consider it skeptically. (There are probably better HSP90 inhibitors out there who haven't said so, and HSP90 inhibitors might be a bit overzealous and not selective enough to avoid reaching toxicity before effectiveness.) Still, 60% even in a small group of KRAS patients is better than anything else I've heard of for KRAS.

http://clinicaltrials.gov/ct2/show/NCT01031225 (ganetesipib)
http://clinicaltrials.gov/ct2/show/NCT01348126 (ganetespib + docetaxel)
FWIW, the above has been discussed briefly on both cancergrace.organd inspire.com.

And below is a laundry list of other drugs and combos that I tabulated are being explored either in the lab or in trials. I don't know if any look "promising" yet and most will not have reached clinicial trials yet, but you could google for current details:

selumetinib (AZD6244) & chemo - depends on LKB1
http://www.nature.com/nature/journal/v483/n7391/full/nature10937.html

pemetrexed for KRAS mutant NSCLC - dramatic responses
http://www.newswise.com/articles/kras-gene-mutation-and-amplification-statu s-affects-sensitivity-to-antifolate-therapy

review of combos for KRAS - dual PI3K-AKT-mTOR & RAS-MEK-ERK promising
http://clincancerres.aacrjournals.org/content/early/2012/03/03/1078-0432.CC R-12-0461.full.pdf+html

review of combos for KRAS - dual PI3K-AKT & MEK-ERK promising
http://clincancerres.aacrjournals.org/content/early/2012/03/03/1078-0432.CC R-12-0461.full.pdf+html

GSK1120212 for KRAS
http://www.ncbi.nlm.nih.gov/pubmed/22169769
http://clinicaltrials.gov/ct2/show/NCT01362296
http://mct.aacrjournals.org/content/11/3/720

selumetinib (AZD6244 MEK for BRAF) and MK2206(AKT for PIK3CA)
/ AZD6244 (MEK) & MK-2206 (AKT) inhibition in RAS cancers
http://pharmastrategyblog.com/2011/10/update-on-mek-and-akt-inhibition-in-r as-driven-cancers.html/

GDC-0973 plus GDC-0941
http://cancerres.aacrjournals.org/content/72/1/210.short

salirasib (KD032)
http://www.marketwatch.com/story/kadmon-acquires-first-in-class-ras-antagon ist-from-concordia-pharmaceuticals-2012-01-09

rapamycin (mTOR inhibitor) plus IPI-504 (HSP90 inhibitor) for KRAS
http://www.sciencedaily.com/releases/2011/09/110912153218.htm
http://mct.aacrjournals.org/content/early/2011/11/04/1535-7163.MCT-11-0578

Nexavar (sorafenib) -- Sorafenib fails to improve KRAS PFS or OS
http://medicalxpress.com/news/2012-01-sorafenib-effective-patients-non-smal l-cell.html

AZD-6244 NSCLC phase II results
http://www.biotechnologyevents.com/node/334

Pre-clinical - selumetinib (AZD6244) & vorinostat for KRAS colon cancer
http://www.ncbi.nlm.nih.gov/pubmed/22173548

Best hopes,

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P.S. -- You may also appreciate this older reference to KRAS thoughts:
http://www.inspire.com/groups/lung-cancer-survivors/discussion/kras-and-the -need-to-step-away-from-inspire?reply_sort=asc&page=1#cmnt_2741806

Best hopes,

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Hi Guys

I was reviewing the ESMO LC conference "poster" videos - and one of the doctors mentions some promising developments re combining HSP90 + mTor inhibitors - just wondered if any one had found/seen the actual study anywhere?


Thanks

Ben

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Duh - sorry Craig - as usual you gave the info I needed just to dumb to see it first reading

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I have exact same diagnosis, but have had excellent response from Alimta/Gemzar Chemo combo.

(Tumors reduced by 30-50% after first 2 months.) Feel fine, no weight or hair loss.

Have had to learn to manage side effects, but definitely worth it!

Debbie
eyeontheball

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A new experimental treatment that might be hopeful, though not yet in clinical trials, is this:
https://www.inspire.com/groups/lung-cancer-survivors/discussion/kras-resear ch-velcade-bortezomib-or-fasudil-via-gata2/

Best hopes,

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