ASCO 2019 Abstracts of Interest

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Pyro70
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Joined: Mon Jan 21, 2019 4:25 pm

ASCO 2019 Abstracts of Interest

Postby Pyro70 » Thu May 16, 2019 2:32 pm

I went through the 200+ CRC abstracts released yesterday ahead of the ASCO 2019 annual meeting. I thought the following three abstracts were the most interesting and thought I’d share:

A phase I study of PolyPEPI1018 vaccine plus maintenance therapy in patients with metastatic colorectal cancer with a predictive biomarker (OBERTO).
https://meetinglibrary.asco.org/record/171761/abstract
Very interesting, but very early (only 2 responders). Hopefully there will be updated data within 12 months. I would think this will be also paired with checkpoint blockade. Clinicaltrial.gov says this trial is still recruiting, if anyone pursues this trial please let me know.

A phase II study of ipilimumab and nivolumab with radiation in microsatellite stable (MSS) metastatic colorectal adenocarcinoma (mCRC).
https://meetinglibrary.asco.org/record/171193/abstract
Seems like a tough treatment - but likely worthwhile if it can elicit a durable response. What’s interesting is that disease control was defined as control outside of the radiation field. So I guess this means RT was sensitizing the immune system so that immunotherapy works even on tumors not irradiated. It’s not clear to me if they are using SBRT or just normal RT. If it’s SBRT it’s probably well tolerated.

CCTG CO.26: Updated analysis and impact of plasma-detected microsatellite stability (MSS) and tumor mutation burden (TMB) in a phase II trial of durvalumab (D) plus tremelimumab (T) and best supportive care (BSC) versus BSC alone in patients (pts) with refractory metastatic colorectal carcinoma (rmCRC).
https://meetinglibrary.asco.org/record/171174/abstract
This forum had discussions about immunotherapy for MSS CRC with high TMB. This abstract sheds some light on the topic.
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

Rock_Robster
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Location: Melbourne, Australia

Re: ASCO 2019 Abstracts of Interest

Postby Rock_Robster » Thu May 16, 2019 6:41 pm

Thanks Pyro70, very interesting.

Pyro70 wrote:It’s not clear to me if they are using SBRT or just normal RT. If it’s SBRT it’s probably well-tolerated

In the study design it’s shown as 8 Gy x 3 so I’m presuming this is indeed SBRT. Would be a strange RT regime otherwise?
Male 37; Melbourne, Australia
10/2018 Dx 3.5cm RC adenocarcinoma, 12cm from AV
Mod diff, EMVI+ LVI+ PNI-
3 LN; 4 liver mets, resectable
pT3pN1apM1a; Stage IVa. MSS, NRAS (G13R)
CEA: Oct-18= 12; Nov-18= 14, Mar-19= 2.4, Aug-19 <2.0
11/18 - FOLFOX x 6
3/19 - Liver resection
4-5/19 - 25 x pelvic radiation; complete met. response, TRG 3
07/19 - ULAR (robot), temp ileo, 1/27 LN+
08/19 - Missed liver spot
08/19 - FOLFOX x 1, FOLFOXIRI x 1, FOLFIRI x 2
10/19 - Planned liver resection #2 & ileo reversal

Pyro70
Posts: 143
Joined: Mon Jan 21, 2019 4:25 pm

Re: ASCO 2019 Abstracts of Interest

Postby Pyro70 » Thu May 16, 2019 8:16 pm

Rock_Robster wrote:Thanks Pyro70, very interesting.

Pyro70 wrote:It’s not clear to me if they are using SBRT or just normal RT. If it’s SBRT it’s probably well-tolerated

In the study design it’s shown as 8 Gy x 3 so I’m presuming this is indeed SBRT. Would be a strange RT regime otherwise?


Yeah, I guess so. What’s interesting about this is that if it helps for MSS, one would think it also improves response rates for MSI cancers. I wonder how many oncologists will try adding some SBRT to immunotherapy even before we get more data.
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

Rock_Robster
Posts: 282
Joined: Thu Oct 25, 2018 5:27 am
Location: Melbourne, Australia

Re: ASCO 2019 Abstracts of Interest

Postby Rock_Robster » Thu May 16, 2019 8:32 pm

Indeed Pyro70, if the SBRT is well-tolerated then it would be tempting.

It reminds me a bit of the Total Body Irradiation given before bone marrow transplants for leukaemia, except that the intent is entirely the opposite - to suppress the immune system prior to transplant. Will be fascinating to see how (if) radiation could also actually sensitise the immune system to tumour cells.
Male 37; Melbourne, Australia
10/2018 Dx 3.5cm RC adenocarcinoma, 12cm from AV
Mod diff, EMVI+ LVI+ PNI-
3 LN; 4 liver mets, resectable
pT3pN1apM1a; Stage IVa. MSS, NRAS (G13R)
CEA: Oct-18= 12; Nov-18= 14, Mar-19= 2.4, Aug-19 <2.0
11/18 - FOLFOX x 6
3/19 - Liver resection
4-5/19 - 25 x pelvic radiation; complete met. response, TRG 3
07/19 - ULAR (robot), temp ileo, 1/27 LN+
08/19 - Missed liver spot
08/19 - FOLFOX x 1, FOLFOXIRI x 1, FOLFIRI x 2
10/19 - Planned liver resection #2 & ileo reversal

Pyro70
Posts: 143
Joined: Mon Jan 21, 2019 4:25 pm

Re: ASCO 2019 Abstracts of Interest

Postby Pyro70 » Fri May 17, 2019 1:50 pm

One more:

ROCKET: A randomized, multicenter phase 2 study of RRx-001 + irinotecan coloreversus regorafenib in 3rd/4th line ctal cancer.
https://meetinglibrary.asco.org/record/171796/abstract

Sounds like they think there is enough evidence for a phase II approval for late stage CRC. I’m glad to see a potential alternative that is better tolerated than regorafenib.
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

Pyro70
Posts: 143
Joined: Mon Jan 21, 2019 4:25 pm

Re: ASCO 2019 Abstracts of Interest

Postby Pyro70 » Sun May 19, 2019 2:17 pm

Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRASG12C inhibitor, in advanced solid tumors.
https://meetinglibrary.asco.org/record/172411/abstract

Promising new agent/trial for anyone with KRAS mutation. KRAS has previously been thought to be “undruggable” but AMGEN found a way to effectively hit the target. Early results show stable disease in 4/4 CRC patients.
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

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juliej
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Re: ASCO 2019 Abstracts of Interest

Postby juliej » Thu May 23, 2019 4:58 pm

Thanks, Pyro70, for posting these! :D :D :D

They are a big help to those of us who do research!

Juliej
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 6/13/2019, CEA<1

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LPL
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Location: Europe

Re: ASCO 2019 Abstracts of Interest

Postby LPL » Fri May 24, 2019 7:12 am

Pyro70 wrote:Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRASG12C inhibitor, in advanced solid tumors.
https://meetinglibrary.asco.org/record/172411/abstract

Promising new agent/trial for anyone with KRAS mutation. KRAS has previously been thought to be “undruggable” but AMGEN found a way to effectively hit the target. Early results show stable disease in 4/4 CRC patients.

This new agent/trial is probable not for “anyone with KRAS mutation” !

I would like to share a conversation about this trial from another forum.
... News on AMG510..
https://www.statnews.com/2019/05/15/amg ... r-protein/

Member A:
”This is a very early but important 1st step. It's only good for G12C which is 4% of patients but it's likely that they'll move to create variants to treat other KRAS mutations as well.”

Member B (caregiver to a patient in that trial):
”it is very hard to tackle the KRAS protein. due to the Cysteine residue at the mutation point created a pocket is just big enough to create an inhibitor/ molecule..other residues just don't have the geometry to allow room do so. It will need to find another mechanism to do something similar”

Me:
”[Member B] thank you for sharing this about the cysteine.. So I interpret this as there is a better chance of developing a drug for people with a C at the end of their mutation? Sorry if I misunderstand..”

Member B:
”[LPL] this cysteine target was discovered through screening process. Scientist looked at all the combinations of possible mutation on the KRAS protein they found a pocket by the C mutation. every protein has different shape, but for KRAS, because it is smooth like a ball, they were trying to find the biggest dent in the ball. .. Cysteine had the optimal geometry for entry into KRAS protein”
DH @ 65 DX 4/11/16 CC recto-sigmoid junction
Adenocarcenoma pt 35x15x9mm G3(biopsi) G1(surgical)
Mets 3 Liver resectable
T4aN1bM1a Stage IVa 2/9 LN
MSS, KRAS-mut G13D
CEA & CA19-9: 5/18 2.5 78 8/17 1.4 48 2/14/17 1.8 29
4 Folfox 6/15-7/30 (b4 liver surgery) 8 after
CT: 8/8 no change 3/27/17 NED->Jan-19 mets to lung
:!: Steroid induced hyperglycemia dx after 3chemo
Surgeries 2016: 3/18 Emergency colostomy
5/23 Primary+gallbl+stoma reversal+port 9/1 Liver mets
RFA 2019: Feb lung met

Pyro70
Posts: 143
Joined: Mon Jan 21, 2019 4:25 pm

Re: ASCO 2019 Abstracts of Interest

Postby Pyro70 » Fri May 24, 2019 1:58 pm

LPL wrote:
Pyro70 wrote:Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRASG12C inhibitor, in advanced solid tumors.
https://meetinglibrary.asco.org/record/172411/abstract

Promising new agent/trial for anyone with KRAS mutation. KRAS has previously been thought to be “undruggable” but AMGEN found a way to effectively hit the target. Early results show stable disease in 4/4 CRC patients.

This new agent/trial is probable not for “anyone with KRAS mutation” !



Yes. Thanks for clarifying. It’s only for a subset of patients with that KRAS mutation.

What forum was this discussion on?
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

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LPL
Posts: 650
Joined: Fri Apr 22, 2016 12:49 am
Location: Europe

Re: ASCO 2019 Abstracts of Interest

Postby LPL » Fri May 24, 2019 6:15 pm

Pyro70,
It was in the FaceBook forum Colontown, in the group ”Tom’s MSS Clinical Trials 4 CRC”.
DH @ 65 DX 4/11/16 CC recto-sigmoid junction
Adenocarcenoma pt 35x15x9mm G3(biopsi) G1(surgical)
Mets 3 Liver resectable
T4aN1bM1a Stage IVa 2/9 LN
MSS, KRAS-mut G13D
CEA & CA19-9: 5/18 2.5 78 8/17 1.4 48 2/14/17 1.8 29
4 Folfox 6/15-7/30 (b4 liver surgery) 8 after
CT: 8/8 no change 3/27/17 NED->Jan-19 mets to lung
:!: Steroid induced hyperglycemia dx after 3chemo
Surgeries 2016: 3/18 Emergency colostomy
5/23 Primary+gallbl+stoma reversal+port 9/1 Liver mets
RFA 2019: Feb lung met

Pyro70
Posts: 143
Joined: Mon Jan 21, 2019 4:25 pm

Re: ASCO 2019 Abstracts of Interest

Postby Pyro70 » Sun Jun 02, 2019 12:58 pm

Regorafenib plus nivolumab in patients with advanced gastric (GC) or colorectal cancer (CRC): An open-label, dose-finding, and dose-expansion phase 1b trial (REGONIVO, EPOC1603).

https://meetinglibrary.asco.org/record/172421

29% ORR in MSS CRC (7 out of 24 patients). Just wow, right?
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak


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