BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

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DK37
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BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby DK37 » Wed May 18, 2016 4:47 pm

Announcement here (THIS IS BIG NEWS!)

Big ASCO MSS-CRC Immunotherapy Abstract out

Rumors hearing since January were correcrt - a pretty high response rate and they focussed on KRAS-mutant patients. Since they did not test in KRAS-wildtype, it is not known how they would respond (missing data)

~Only tested in KRAS-Mutant. MOST/All were MSS-CRC

17% had PR ("partial response" at least 30% tumor shrinkage). An additional 22% had Stable Disease.
Combining those two together: 40% had disease control!!

http://abstracts.asco.org/176/AbstView_176_171295.html

This is the first (hopefully of many!) steps forward for MSS-CRC immunotherapies!

WOO-HOO! BIG DAY!!

More details will follow - I am busy pushing this out to people ASAP.
Last edited by DK37 on Thu May 19, 2016 12:02 am, edited 2 times in total.
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
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Nik Colon
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Re: BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby Nik Colon » Wed May 18, 2016 4:57 pm

AWESOME! Thanks DK!!! :mrgreen:
KRAS-mut G12V,MSS
Stage IVa Sig CC 2 lvr mets 1/12 Ln
(3, =<3 lng spots at dx til 5/16)
=T3N1aM1a 4cmX4mm (lng not included)
dx 12/2014 at age 39
CEA 1/15-4.9, 12/16-4.9 again
neoadj FOLFOX 1/15-3/15 (4tx, 3w/1wo oxi)
Col/Lvr surg 4/23/15 NED
adj FOLFIRI start 6/15-9/15 (8tx, 5w/3wo iri)
1 sml lvr spot/cyst
12/6/16 multi lung spots/mets?
No longer NED :(
My tx ongoing-start 1/20/15
Adding your SIGNATURE, etc

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juliej
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Re: BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby juliej » Wed May 18, 2016 5:10 pm

Thanks for posting this, DK! This is the one I was most excited about - a MEK inhibitor/PD1 combotherapy for MSS-CRC. It's about time! I can't wait to read their presentation when it's released. Please post the details if you have access to it.

For those who are curious, the two drugs are Atezolizumab and Cobimetinib. There are 23 study locations - all are recruiting patients right now! Here is the link in case someone is interesting in joining the study: NCT01988896

And here is the conclusion at the end of the abstract! :D
The combination of cobi and atezo in CRC is well tolerated at the maximum administered doses. These results show that pts with MSS CRC can respond to the combination of cobi and atezo, and provide support for continued evaluation of the combination. Clinical trial information: NCT01988896
Stage IV, liver/lung mets 8/4/2010
Xelox+Avastin 8/18/10 to 10/21/11
LAR, liver resec, HAI pump 11/11
Double lung surgery + ileo reversal 2/12
Adjuvant Xeloda 3-9/12
VATS rt. lung 12/21/12 - benign granuloma!
NED 3/17/12 to 7/13/2018, CEA<1

Maddielolo
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Re: BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby Maddielolo » Wed May 18, 2016 5:22 pm

huge and important step. This means more research, more money, and more future success. And hope. The combo therapies are certainly ones to watch and investigate

Steph20021
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Re: BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby Steph20021 » Wed May 18, 2016 6:58 pm

Very cool. DK do you see any hope for us MSS non-mutants anywhere down the pipeline?
DX 1/31/14 @ 33- SPS-T4a(invades visceral peri), N2a(6/106 LN), M1a(ovary) (Stage 4a) MSS; BRAF V600E mutation
2/1/14-subtotal col, lost R ovary, temp ileo
3/14-9/14- folfox; sepsis
11/14-CT/PET: L ovary met, pelvic met, (?)ghost liver met(?)
12/14-folfiri -13 rds kept me stable from 3/15-6/15
8/15-HIPEC, hysterectomy et al, 2nd temp ileo, NED?
09/15- cea 0.9
05/16- recurrence in abdo wall and lymph nodes
Jan/17- pulmonary embolism
Feb/17- 1 wk radiation to abdo wall
Aug/16- on folfiri
Jan/18-folfox

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DK37
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Re: BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby DK37 » Thu May 19, 2016 12:01 am

Steph20021 wrote:Very cool. DK do you see any hope for us MSS non-mutants anywhere down the pipeline?


Yes I do!

- First of all, with this combination (MEK + PDL1) they have not tested it in KRAS-wildtype patients so it may have some level of activity in those patients too. There is no clinical activity saying one way or another. There are KRAS-wildtype models where it does work (published)

- Scientists strongly believed this would be true all along - cotherapies would be identified with MSS-CRC clinical activity. As I have said on Colon Talk continuously, there are just "too many shots on goal" with strong animal model data for them all to fail. :-) Clinicians and patients are now seeing this. A match has just been thrown on a Hope gasoline puddle. today's results also implies (logically) that there will be additional co-therapies which will work. It is illogical to assume that only a MEK inhibitor will work (as an outlier). The immune system wants to attack MSS-CRC… you just need to cycle through enough appropriate co-therapy drugs to find out the right combination. Maybe KRAS-wildtype needs a different co-therapy - well multiple different co-therapies are in clinical trials or approaching them quickly as we speak. I firmly believe it is a solvable problem – we’re not talking cold fusion here.

I think this will probably open up the flood gates at other companies for significantly more MSS trials. More trials will be started now since they see that a co-therapy CAN work in MSS-CRC, similar to what happened at ASCO-2015 when seeing MSI-high PD1 activity opened up many more trials for them. MSS-CRC is a BIG patient population… companies like that, especially once de-risked a bit by today’s study results.

-DK
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
DK37 Science Posts List

Orissia
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Re: BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby Orissia » Thu May 19, 2016 5:17 am

Huge news! Thanks so much for sharing this Tom. I hope they find something for Kras wildtypes too.
Stage 4 colon cancer w. mets to liver
No surgeries, primary tumour & mets still in situ
MSS, KRAS wild type (normal)
2014 Folfox w. Avastin
2015 Folfiri w. Zaltrap
2016 Erbitux fail
June 2016 SIRT done; approved for TAS 102/ Lonsurf
Looking to participate in MSS immuno trial when they start recruiting, if Lonsurf fails


Married since 2007 with a 8 year old daughter.

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BrownBagger
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Re: BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby BrownBagger » Thu May 19, 2016 6:01 am

Thank you, Tom!
Eric, 58
Dx: 3/09, Stage 4 RC
Recurrences: (ongoing, lung, bronchial cavity, ribs)
Major Ops: 6/ RFA: 3 /bronchoscopies: 8
Pelvic radiation: 5 wks. Bronchial radiation—brachytheray: 3 treatments
Chemo Rounds (career):136
Current Chemo Cocktail: Xeloda & Erbitux & Irinotecan biweekly
Current Cocktail; On the Wagon (mostly)
Bicycle miles post-dx 10,477
Motto: Live your life like it's going to be a long one, because it just might, and then you'll be glad you did.

khadars
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Re: BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby khadars » Thu May 19, 2016 7:28 am

Bless you Tom. Having the right information is half the battle with Stage IV MSS-CRC! Gives us a chance to spend more time with loved ones! Best.
3/2015 - Rectal Cancer @ 26yr old.
5/2015 - Clinical Trial (FOLFOX Only)
9/2015 - LAR with TME (Stage IIIB, RC) w/ Loop Ileostomy
2/2016 - Ileostomy Reversal
5/2016 - Stage IVb

saffa
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Re: BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby saffa » Thu May 19, 2016 4:09 pm

I emailed the contact for NCT01988896 and they seem to be no longer recruiting? :( Hopefully there will be other trials coming up shortly...

"Hello,

Thank you for the opportunity to respond to your inquiry regarding clinical trial, GP28363, NCT01988896, Study of Atezolizumab in Combination With Cobimetinib in Participants With Locally Advanced or Metastatic Solid Tumors.

Unfortunately the study you are interested in is no longer recruiting. You may wish to review the following websites for additional trials: www.clinicaltrials.gov and www.centerwatch.com. These are where other pharmaceutical companies and educational facilities frequently post their studies, you may find one of interest.

I apologize for not being able to assist you directly and wish you the best of health.

Trial Information Support Line (TISL)"
25 yo Female diagnosed 10/10/15 Stage IV (sigmoid primary and liver mets inoperable)
KRAS-mut (G12V) Tp53-mut MSS
Folfox 10/15-04/16
HAI/LAR @ MSK 02/16
CEA rising
Lung nodules confirmed 05/16
Switch to Folfiri/FUDR/Mitomycin 05/16
Looking for clinical trials
CEA dropped from 842 (05/02/16) to 257 (06/29/16) - scan confirms liver and lung shrinkage

khadars
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Re: BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby khadars » Thu May 19, 2016 5:15 pm

cobimetinib was approved by FDA last year, and atezolizumab was approved yesterday. i'm sure that if you find a way to convince your doctor to ask you to give you the drugs, it's possible.

i'm sorry that a clinical trial is not possible.
3/2015 - Rectal Cancer @ 26yr old.
5/2015 - Clinical Trial (FOLFOX Only)
9/2015 - LAR with TME (Stage IIIB, RC) w/ Loop Ileostomy
2/2016 - Ileostomy Reversal
5/2016 - Stage IVb

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DK37
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Re: BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby DK37 » Sat May 21, 2016 9:08 am

saffa wrote:I emailed the contact for NCT01988896 and they seem to be no longer recruiting? :( Hopefully there will be other trials coming up shortly...

"Hello,

Thank you for the opportunity to respond to your inquiry regarding clinical trial, GP28363, NCT01988896, Study of Atezolizumab in Combination With Cobimetinib in Participants With Locally Advanced or Metastatic Solid Tumors.

Unfortunately the study you are interested in is no longer recruiting. You may wish to review the following websites for additional trials: http://www.clinicaltrials.gov and http://www.centerwatch.com. These are where other pharmaceutical companies and educational facilities frequently post their studies, you may find one of interest.

I apologize for not being able to assist you directly and wish you the best of health.

Trial Information Support Line (TISL)"



Yes - this is a TEMPORARY situation while they switch over from a Phase 1 trial to confirmatory Phase 2 trials. Only the Phase 1 trial has closed. We'll all keep an eye on clinicaltrials.gov for the Phase 2 trial opening up (I am very sure very soon). They may make a press announcement in regards to it at the ASCO conference. Don't worry - this is such big news, It will be followed up on --- and it will be followed up on quickly! -DK
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
DK37 Science Posts List

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DK37
Posts: 510
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Re: BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby DK37 » Sat May 21, 2016 9:14 am

khadars wrote:cobimetinib was approved by FDA last year, and atezolizumab was approved yesterday. i'm sure that if you find a way to convince your doctor to ask you to give you the drugs, it's possible.

i'm sorry that a clinical trial is not possible.


As I just mentioned a minute ago, there will be a confirmatory Phase 2 trial starting up very soon. It was amazing timing that now all components are commercially available - opening up the possibility of potential compassionate use discussions with MD teams... That is an area I do not know a lot about but worth discussing with your MD for his/her medical advice once the final ASCO data is released on June 4.

-DK
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
DK37 Science Posts List

jortego128
Posts: 284
Joined: Sat Aug 15, 2015 7:47 am

Re: BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)

Postby jortego128 » Sun May 29, 2016 7:20 am

Fantastic news, far more response than PD-1i alone for MSS. I cant wait to hear some success stories from members who get on one of the trials.

If only my mom could have had a little more time, 10 months is so unfair. She was KRAS-mutant, but her CRC was apparently ultra-aggressive.
DM 57 yrs old dx 6/8/15 T:4a N:1b M:1
KRAS G12D and TP53 C242fs mutations
Poorly Differentiated, Prominent Signet Ring Component(~50%)
Microsatellite Stable, 3 of (13)lymph nodes positive
15 Liver mets, largest 3.2 cm
Prim. Resection, Right Hemicolectomy 6/21/15
Start Chemo 7/20/15
2 rounds FOLFOX, 1 round FOLFOX +Avastin
CT 8/28/15, met growth, largest 4.5cm
4 rounds FOLFOX+Avastin
CT 11/06/15 mets stable, lungs clear
Begin FOLFIRI+Avastin 11/17/15, Stop chemo 1/26/16
Entered Paradise 3/11/2016


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