Stage 4 and Progressing - Advice Appreciated

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inorganic8
Posts: 42
Joined: Mon Feb 27, 2017 6:13 pm

Stage 4 and Progressing - Advice Appreciated

Postby inorganic8 » Wed Dec 06, 2017 1:52 pm

Hey,

DH has stage 4 cancer in his sigmoid colon. It has spread to the peritoneal cavity. He has been on folfirinox and folfiri. The folfirinox worked for a while, but his disease is now progressing. We spoke with a HIPEC surgeon today and he was hesitant, but will do a laparoscopic inspection before he makes up his mind. So I am working on plan B. Here are the basics: KRAS G12D, MSS.

I am looking into the TIL trial in Bethesda. I see some discussion on this board about MGD-something coupled with Keytruda. Any thoughts, advice, ideas, I'd greatly appreciate.

-Kim
Wife to wonderful man with CRC
Stage IV Diagnosis 1/27/17, Mets to Liver, Omentum, Peri
KRAS Mutation, G12, MSS
Folfirinox 2/8/17, completed 9 rounds
Follow-Up PET 4/13/17 - Very encouraging. Definite shrinkage and 2/3 liver mets resolved.
Follow-Up PET 6/13/17 - Very encouraging. Even more shrinkage.
Folfiri 6/14/17
November Scan - disease progression
Looking for clinical trial

NHMike
Posts: 691
Joined: Fri Jul 21, 2017 3:43 am

Re: Stage 4 and Progressing - Advice Appreciated

Postby NHMike » Wed Dec 06, 2017 7:55 pm

The National Cancer Institute TIL trials require either HLA-C*08:02 or HLA-A*11:01 Alleles so I would assume that they would test for these. The known Alleles that present KRAS G12D to the cell surface are listed below. There is a long thread for these trials on this forum. The HLA-C*08:02 allele has higher representation from parts of Europe, West Africa, and South Africa. The HLA-A*11:01 has higher representation in East Asia. I plan to get tested for these alleles.

Image

The other interesting trial is the Roche trial for solid tumors using something like a synthetic antigen based on CEA. There's a thread for this here as well though the original poster didn't think that it was successful based on some of the people that he knows. I did see that Roche is working on staffing for this trial.

BTW, I have KRAS G12D as well so I regularly look around for information on it. It is the most common CRC gene mutation and the most common KRAS mutation.

KRAS represents the most frequently mutated oncogene across all cancer types. The KRAS G12D and KRAS G12V mutated alleles are found in 90% of patients with pancreatic cancer, which is a major unmet need. Ar esurgence of interest in targeting KRAS has emerged from the NCI, leading to the RAS Initiative led by Frank McCormick. Our efforts have led to progress on drugging
one particular allele, KRAS G12C, by relying on the presence of a nucleophilic cysteine residue for drug binding. KRAS G12C accounts for an estimated 29,700 new cancer diagnoses (lung and colon most frequently) compared with 53,700 and 39,100 for KRAS G12D and KRAS G12V, respectively. The current need is to develop KRAS inhibitors that do not rely on covalent attachment to
Cys12, that is, the Asp12 and Val12 mutants.

https://www.nature.com/articles/nrc.201 ... 7RIQ%3D%3D
6/23/17: ER rectal bleeding; Colonoscopy+Biopsy
7/13: Stage 3B rectal cancer. T3, N1b, M0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6 mm, 5 x 5 mm
7/31-9/8: Xeloda 3,400 mg/day+radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8. 11/30: 0.6
MSS, KRAS G12D
10/6: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 mm (-75%), 5 x 3 mm (-40%). 5.1 CM from AV
10/30: Surgery: LAR, Temp Ileostomy
Path report: Tumor regression grade: 0 (complete response).


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