Clinical Trial NIVOLUMAB for Non MSI-H

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PeterG
Posts: 52
Joined: Tue Feb 03, 2015 12:32 pm

Clinical Trial NIVOLUMAB for Non MSI-H

Postby PeterG » Tue Apr 25, 2017 6:58 pm

Following discussions with my oncologist about how Nivolumab was not being tested on those of us CRC partients without microsatellite instability, I did a search on the MSS-CRC Immuno Trial Finder, and lo, NCT02060188 is open to--specifically seeks--MSI Negative Colorectal Cancer patients. Is anyone on this list participating in this trial? Anyone know anything about success with Nivolumab with non MSI-H patients (I understood before that non-MSI-H cancers were not responsive to Nivolumab/checkpoint inhibitors--this was an exclusion factor in some of the trials we had reviewed.) I am non-MSI-High, and my oncologist has begun inquiries for me re: NCT02060188. Would love to communicate with those in the know.
DX Aug. 2013 Resection 09/13.
08/14 CT : .7 CM pulmonary nodule--& multiple nodules.
03/15 15 dendritic cell vaccine-monthly
05/16 begin 3000 MG Xeloda & Avastin
11-16 shrinkage.”Sstable"
2/2017: Port installed. Begin Folfiri and Avastin
8/2017: Xeloda, Avastin and Iranotican. 3-wk cycle.
2-6-18: small pulmonary embolim—some growth in one pulmonary tumor. Start Xarelto.
2-8-18 : Change of chemo: Xeloda with Oxaliplatin no avastin.
9/2018: Tumor growth. Begin Stivarga.

User avatar
Maia
Posts: 2443
Joined: Fri Aug 24, 2012 8:00 am

Re: Clinical Trial NIVOLUMAB for Non MSI-H

Postby Maia » Sat Apr 29, 2017 12:56 pm

Hi, Peter

The trial you mention, NCT02060188, CheckMate142 is not just Nivolumab for MSS (that would have little chances to work: nivolumab monotherapy works well for most MSI-H, but not on itself for MSS). The trial proposed *combinations* of drugs.


It has TWO arms for MSS --that is non MSI-High-- colorectal cancer:

- Cohort C4: Nivolumab (Nivo) + Ipilimumab (Ipi) + Cobimetinib: one immunotherapy (nivolumab, brand name Opdivo, FDA approved for other cancers; an anti-PD-1) + ipilimumab (other immunotherapy, brand name Yervoy, FDA approved for melanoma; anti CTLA-4) + a MEK inhibitor (cobimetinib, brand name Cotellic, FDA approved against melanoma; a pill)

- Cohort C6: Nivolumab + Daratumumab . Daratumumab is an anti-CD38 monoclonal antibody (FDA approved for multiple myeloma, trade name Darzalex).

This first confirmed responses for immuntherapy, leaving aside the TIL trial at Bethesda, came from the combination of a checkpoint inhibitor (an anti PD-L1, that one might think equivalent of anti -PD-1 nivolumab or pembrolizumab) plus cobimetinib: http://meetinglibrary.asco.org/content/171295-176

Cobimetinib Plus Atezolizumab Active in Microsatellite Stable mCRC http://www.onclive.com/conference-cover ... table-mcrc

I do know someone from other group in this trial, who joined past January, is receiving the Nivo+Ipi+cobi combination, and reported past March that
CEA dropped by half and CT scan showed that some tumors shrank a bit! First time in nearly 2 years that scans did not show cancer growth.

Edited to add: this is an 'old' trial and the investigators changed the protocol past October to include cobimetinib --the arm 4-- and just one month ago to include the arm 6-- so that is why you won't find too much data about it yet, and nothing about arm 6. I think something is going to be published next June at ASCO annual meeting.

PeterG
Posts: 52
Joined: Tue Feb 03, 2015 12:32 pm

Re: Clinical Trial NIVOLUMAB for Non MSI-H

Postby PeterG » Sun Apr 30, 2017 10:04 pm

The trial you mention, NCT02060188, CheckMate142 is not just Nivolumab for MSS (that would have little chances to work: nivolumab monotherapy works well for most MSI-H, but not on itself for MSS). The trial proposed *combinations* of drugs.


It has TWO arms for MSS --that is non MSI-High-- colorectal cancer:

- Cohort C4: Nivolumab (Nivo) + Ipilimumab (Ipi) + Cobimetinib: one immunotherapy (nivolumab, brand name Opdivo, FDA approved for other cancers; an anti-PD-1) + ipilimumab (other immunotherapy, brand name Yervoy, FDA approved for melanoma; anti CTLA-4) + a MEK inhibitor (cobimetinib, brand name Cotellic, FDA approved against melanoma; a pill)

- Cohort C6: Nivolumab + Daratumumab . Daratumumab is an anti-CD38 monoclonal antibody (FDA approved for multiple myeloma, trade name Darzalex).

This first confirmed responses for immuntherapy, leaving aside the TIL trial at Bethesda, came from the combination of a checkpoint inhibitor (an anti PD-L1, that one might think equivalent of anti -PD-1 nivolumab or pembrolizumab) plus cobimetinib: http://meetinglibrary.asco.org/content/171295-176

Cobimetinib Plus Atezolizumab Active in Microsatellite Stable mCRC http://www.onclive.com/conference-cover ... table-mcrc

I do know someone from other group in this trial, who joined past January, is receiving the Nivo+Ipi+cobi combination, and reported past March that
CEA dropped by half and CT scan showed that some tumors shrank a bit! First time in nearly 2 years that scans did not show cancer growth.

Edited to add: this is an 'old' trial and the investigators changed the protocol past October to include cobimetinib --the arm 4-- and just one month ago to include the arm 6-- so that is why you won't find too much data about it yet, and nothing about arm 6. I think something is going to be published next June at ASCO annual meeting.


Thanks Maia--I had seen that it was a "cocktail" but had been quite inarticulate in my posting, upon reflection. (And I had read it as Cohort 6 only for MSS, but again, generally hasn't been my wheelhouse.) By paper next June, do you mean June 2017? I suppose I am grasping at straws--we all are, to some degree--hoping that, as an MSS patient, I can be treated with checkpoint inhibitors that might stand a chance, before my tumors kill me (I hope that doesn't sound overly melodramatic, because writing it that way sure did.) Apparently I am going to have problems not being eliminated from trials at this point, anyhow, because most trials require failure on folifiri or folofox--is this correct? What do you (or anyone) know about clinical trials with checkpoint inhibitors on MSS patients? Again, sorry for my unfamiliarity with the research, and potentially ignorant questions. I really do appreciate your insight!
DX Aug. 2013 Resection 09/13.
08/14 CT : .7 CM pulmonary nodule--& multiple nodules.
03/15 15 dendritic cell vaccine-monthly
05/16 begin 3000 MG Xeloda & Avastin
11-16 shrinkage.”Sstable"
2/2017: Port installed. Begin Folfiri and Avastin
8/2017: Xeloda, Avastin and Iranotican. 3-wk cycle.
2-6-18: small pulmonary embolim—some growth in one pulmonary tumor. Start Xarelto.
2-8-18 : Change of chemo: Xeloda with Oxaliplatin no avastin.
9/2018: Tumor growth. Begin Stivarga.

ronnieciao
Posts: 95
Joined: Sat Nov 08, 2014 1:58 pm
Location: Northern Italy and UK

Re: Clinical Trial NIVOLUMAB for Non MSI-H

Postby ronnieciao » Mon May 01, 2017 6:02 am

PeterG wrote:
The trial you mention, NCT02060188, CheckMate142 is not just Nivolumab for MSS (that would have little chances to work: nivolumab monotherapy works well for most MSI-H, but not on itself for MSS). The trial proposed *combinations* of drugs.


It has TWO arms for MSS --that is non MSI-High-- colorectal cancer:

- Cohort C4: Nivolumab (Nivo) + Ipilimumab (Ipi) + Cobimetinib: one immunotherapy (nivolumab, brand name Opdivo, FDA approved for other cancers; an anti-PD-1) + ipilimumab (other immunotherapy, brand name Yervoy, FDA approved for melanoma; anti CTLA-4) + a MEK inhibitor (cobimetinib, brand name Cotellic, FDA approved against melanoma; a pill)

- Cohort C6: Nivolumab + Daratumumab . Daratumumab is an anti-CD38 monoclonal antibody (FDA approved for multiple myeloma, trade name Darzalex).

This first confirmed responses for immuntherapy, leaving aside the TIL trial at Bethesda, came from the combination of a checkpoint inhibitor (an anti PD-L1, that one might think equivalent of anti -PD-1 nivolumab or pembrolizumab) plus cobimetinib: http://meetinglibrary.asco.org/content/171295-176

Cobimetinib Plus Atezolizumab Active in Microsatellite Stable mCRC http://www.onclive.com/conference-cover ... table-mcrc

I do know someone from other group in this trial, who joined past January, is receiving the Nivo+Ipi+cobi combination, and reported past March that
CEA dropped by half and CT scan showed that some tumors shrank a bit! First time in nearly 2 years that scans did not show cancer growth.

Edited to add: this is an 'old' trial and the investigators changed the protocol past October to include cobimetinib --the arm 4-- and just one month ago to include the arm 6-- so that is why you won't find too much data about it yet, and nothing about arm 6. I think something is going to be published next June at ASCO annual meeting.


Thanks Maia--I had seen that it was a "cocktail" but had been quite inarticulate in my posting, upon reflection. (And I had read it as Cohort 6 only for MSS, but again, generally hasn't been my wheelhouse.) By paper next June, do you mean June 2017? I suppose I am grasping at straws--we all are, to some degree--hoping that, as an MSS patient, I can be treated with checkpoint inhibitors that might stand a chance, before my tumors kill me (I hope that doesn't sound overly melodramatic, because writing it that way sure did.) Apparently I am going to have problems not being eliminated from trials at this point, anyhow, because most trials require failure on folifiri or folofox--is this correct? What do you (or anyone) know about clinical trials with checkpoint inhibitors on MSS patients? Again, sorry for my unfamiliarity with the research, and potentially ignorant questions. I really do appreciate your insight!


Peter, I can tell you my mother's experience. She was accepted into the Atezolizumab+ Cobimetinib trial, and was randomized into the Atezolizumab (immunotherapy) only arm. Unfortunately it did nothing for her. She was MISS Kras wild.
DD of Mum, 53
Diagnosed CC Stage IVb, October 2014
Mets to liver, peri, ovaries, bones
Folfox + Panitumumab
5fu+Panitumumab
Folfiri + Avastin
Cetuximab monotherapy
Immunotherapy: Tecenriq (Atezolizumab) single agent trial: failed
Left us Feb 2017


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