The Colon Club

Wewillfight wrote:If you guys were to take a shot at one of these combos which would it be?

Stivarga/Opdivo? (REGONIVO)

Avastin/ Opdivo

Avastin or Stivarga / Pembo

Is there any indication that Avastin instead of Stivarga could be more beneificial

Obviously it is a roll of the dice but hoping to weight the dice in favour especially if throwing 20-50k at it

I’m assuming you’re MSS in this response...

I’m not aware of any suggested synergy between Avastin and Opdivo or Pembro. Obviously Avastin is a good drug so no reason not to take it, however also no reason to expect it would make a PD-1 inhibitor work in an MSS patient.

Pembro (Keytruda) and Opdivo are both PD-1 checkpoint inhibitors, so in theory Rego could have a similar sensitising effect with Keytruda that it appears to with Opdivo. There are trials underway now to test this. However given it’s currently untested and you’d be gambling with your own money, I’d personally preference Opdivo.

There are a couple of other things you could consider alongside a PD-1 inhibitor:

1) radiation therapy - there is suggestion (and several trials) that radiation to tumour areas (anywhere in the body) may sensitise the immune system to previously ‘cold’ tumour cells, allowing a PD-1 inhibitor to have therapeutic effect

2) Pixatimod - which is currently in trials with Opdivo with some very early but encouraging results.

Best of luck,
Rob

Wewillfight wrote:If you guys were to take a shot at one of these combos which would it be?

Stivarga/Opdivo? (REGONIVO)

Avastin/ Opdivo

Avastin or Stivarga / Pembo

Is there any indication that Avastin instead of Stivarga could be more beneificial

Obviously it is a roll of the dice but hoping to weight the dice in favour especially if throwing 20-50k at it

The data we have is most compelling for Regonivo.

However a Cape+Bev+PD1 study has hit its primary endpoint and is being explored more. I don’t really know what to make of this data because a similar trial call MODUL was negative.
https://www.targetedonc.com/news/combin ... udies-show

There was also an abstract at ASCO 2019 that showed positive results from PD1+CTLA4+radiation

One could consider combining these
Eg Regonivo+radiation
Regonivo+bevacizumab likely doesn’t make much sense because if the similarities between Ref and Bev

Pixatimod is also interesting, but likely difficult/impossible to get your hands on.

Pyro70 wrote:

Wewillfight wrote:If you guys were to take a shot at one of these combos which would it be?

Stivarga/Opdivo? (REGONIVO)

Avastin/ Opdivo

Avastin or Stivarga / Pembo

Is there any indication that Avastin instead of Stivarga could be more beneificial

Obviously it is a roll of the dice but hoping to weight the dice in favour especially if throwing 20-50k at it

Pixatimod is also interesting, but likely difficult/impossible to get your hands on.

True, unless you happen to be in Australia: https://www.anzctr.org.au/Trial/Registr ... ?id=373869

Rock_Robster wrote:

Pyro70 wrote:

Wewillfight wrote:If you guys were to take a shot at one of these combos which would it be?

Stivarga/Opdivo? (REGONIVO)

Avastin/ Opdivo

Avastin or Stivarga / Pembo

Is there any indication that Avastin instead of Stivarga could be more beneificial

Obviously it is a roll of the dice but hoping to weight the dice in favour especially if throwing 20-50k at it

Pixatimod is also interesting, but likely difficult/impossible to get your hands on.

True, unless you happen to be in Australia: https://www.anzctr.org.au/Trial/Registr ... ?id=373869

True. But you still have to get in the trial. Are you pursuing this? I’m quite disappointed on the slow pace of development of Pixatimod...

Pyro70 wrote:

Rock_Robster wrote:

Pyro70 wrote:True, unless you happen to be in Australia: https://www.anzctr.org.au/Trial/Registr ... ?id=373869

True. But you still have to get in the trial. Are you pursuing this? I’m quite disappointed on the slow pace of development of Pixatimod...

Quite right. I’m very interested in the drug but this trial doesn’t really line up with my treatment plan in terms of both timing and drug selection. I agree the pacing is ridiculously slow - I don’t know if they’re having issues recruiting or what (these are not small hospitals that are involved), but it’s frustrating to say the least.

Pyro70 wrote:Latest results from the Regonivo patients I’m tracking:

*Total of 8 patients had their first scan or have stopped the combo.
*2 patients have a potential response (seeing cavitation, but shrinkage isn’t at the 30% required by RECIST for an official response).
*2 patients are stable
*4 patients have died or entered hospice

One current hypothesis is that patients with a lower performance status and/or more advanced disease don’t perform as well as those that take the combo earlier.

The numbers are excellent! Thanks.

boswind wrote:

Pyro70 wrote:Latest results from the Regonivo patients I’m tracking:

*Total of 8 patients had their first scan or have stopped the combo.
*2 patients have a potential response (seeing cavitation, but shrinkage isn’t at the 30% required by RECIST for an official response).
*2 patients are stable
*4 patients have died or entered hospice

One current hypothesis is that patients with a lower performance status and/or more advanced disease don’t perform as well as those that take the combo earlier.

The numbers are excellent! Thanks.

Why do you consider these numbers to be good? I will be having a meeting with my dad oncologist and debate with him on this regimen but I don't know what is good or bad about these results.

Thanks,
Nate.

natelaugh wrote:

boswind wrote:

Pyro70 wrote:Latest results from the Regonivo patients I’m tracking:

*Total of 8 patients had their first scan or have stopped the combo.
*2 patients have a potential response (seeing cavitation, but shrinkage isn’t at the 30% required by RECIST for an official response).
*2 patients are stable
*4 patients have died or entered hospice

One current hypothesis is that patients with a lower performance status and/or more advanced disease don’t perform as well as those that take the combo earlier.

The numbers are excellent! Thanks.

Why do you consider these numbers to be good? I will be having a meeting with my dad oncologist and debate with him on this regimen but I don't know what is good or bad about these results.

Thanks,
Nate.

Nate, I agree with you. From this data it’s hard to say that Regonivo is much better than Regorafenib monotherapy. But there is some promise in the 25% that seem to have a response despite not having significant shrinkage. Hopefully with more data it will be clearer. Still 50% stability isn’t bad. For me the risk of adding nivolumab is low enough that for anyone considering starting Regorafenib they should add the IO agent.

If there is 25% success rate from this combo that is huge. It might not sound great on the face of it by Opdivo mono-therapy had less than 5% efficacy in MSS patients. This gives patients a big boost

Wewillfight wrote:If there is 25% success rate from this combo that is huge. It might not sound great on the face of it by Opdivo mono-therapy had less than 5% efficacy in MSS patients. This gives patients a big boost

Well the disease control rate is closer to 50%. The question is how does this compare to Regorafenib monotherapy? Unless we see actual responses it’s unclear if the IO component is helping (without a large trial using a Regorafenib control group). Currently the ORR is technically 0% based on RECIST despite some patients clearly benefiting. But we don’t know if they would have benefited anyways on Regorafenib monotherapy.

Pyro70 wrote:

Wewillfight wrote:If there is 25% success rate from this combo that is huge. It might not sound great on the face of it by Opdivo mono-therapy had less than 5% efficacy in MSS patients. This gives patients a big boost

Well the disease control rate is closer to 50%. The question is how does this compare to Regorafenib monotherapy? Unless we see actual responses it’s unclear if the IO component is helping (without a large trial using a Regorafenib control group). Currently the ORR is technically 0% based on RECIST despite some patients clearly benefiting. But we don’t know if they would have benefited anyways on Regorafenib monotherapy.

My first discussion about regonivo regimen with my dad oncologist, he stated the exact thing. "Don't know result with only Regorafenib monotherapy." I had no response because no data.

Nate.

Any recent updates on the patients currently in the Regorafenib/Nivolumab (Regonivo) trial?

meatie wrote:Any recent updates on the patients currently in the Regorafenib/Nivolumab (Regonivo) trial?

The latest numbers I have are:
11 patients had their first scan
7 have progressive disease
4 have stable disease
0 patients have reported an objective response per RECIST

This includes all patients reporting in colontown trying a PD1+Regorafenib. (Ie also includes pembro+Regorafenib). Some patients are in a trial others are doing it off label.

I strongly recommend joining the Colontown MSS Facebook group where there is a much more detailed discussion of the results.

optimist4747 wrote:https://www.targetedonc.com/news/regorafenibnivolumab-combo-to-be-studied-in-phase-iii-trial-of-patients-with-mss-mcrc

Is this phase 3 trial already on clinicaltrials.gov ?