Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
BIO-KRAS-G12C	G12C	IB	SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Poor Outcome) SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance SRC-CIVIC: Level D (Supports, Sensitivity/Response)	KRAS G12C in mCRC (~3-4%): single-agent KRASG12C inhibitors insufficient (intrinsic EGFR feedback). Combination adagrasib + cetuximab (KRYSTAL-1, Yaeger et al. NEJM 2023) ORR 46%, PFS 6.9 mo. Sotorasib + panitumumab (CodeBreaK 300, Fakih et al. NEJM 2023) ORR 26% vs investigator's choice. Both FDA-approved 2024.	adagrasib + cetuximab sotorasib + panitumumab	SRC-NCCN-COLON-2025 SRC-ESMO-COLON-2024

Treatment options (3 tracks)

IND-CRC-ADJUVANT-STAGE2-HIGHRISK-FOLFOX

Indication: IND-CRC-ADJUVANT-STAGE2-HIGHRISK-FOLFOX
Regimen: —
Reason: Alternative track presented for HCP consideration

Standard plan

Indication

IND-CRC-ADJUVANT-STAGE3-FOLFOX

Regimen

FOLFOX (mFOLFOX6)

Drugs + NSZU

Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² · IV over 2h, day 1 · IV ✓ NSZU covered
Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² · IV over 2h, day 1 (concurrent with oxaliplatin) · IV ✓ NSZU covered
5-Fluorouracil (DRUG-5-FLUOROURACIL) 400 mg/m² IV bolus + 2400 mg/m² CIV over 46h · Day 1 bolus, day 1-2 CIV · IV ✓ NSZU covered

Reason

Alternative track presented for HCP consideration

IND-CRC-ADJUVANT-STAGE3-CAPOX

Indication: IND-CRC-ADJUVANT-STAGE3-CAPOX
Regimen: —
Reason: Alternative track presented for HCP consideration

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

Frailty/age profile precluding doublet-intensive or triplet chemo: ECOG ≥3, OR (age ≥80 + Charlson ≥3), OR composite (age ≥75 + albumin <3.0 + ≥2 comorbidities). Triggers de-escalation toward 5-FU/LV mono, capecitabine mono, or best supportive care. RF-CRC-FRAILTY-AGE

CONTRA-AGGRESSIVE

Hard contraindications to escalation

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity

Standard plan (IND-CRC-ADJUVANT-STAGE3-FOLFOX)

Do NOT delay adjuvant beyond 8 weeks post-surgery if avoidable — diminishing benefit thereafter
Do NOT continue oxaliplatin past Grade 2 functional neuropathy — switch to 5-FU/LV alone
Do NOT add bevacizumab in adjuvant — NSABP C-08 negative, NOT a standard

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · FOLFOX (mFOLFOX6)

14-day cycles × 12 cycles (6 mo) for adjuvant stage III; until progression / unacceptable toxicity for metastatic; 4 cycles (8 wk) periop trials

MDT brief

Data quality

Unevaluated RedFlags: RF-CRC-BRAF-V600E-POOR-PROGNOSIS, RF-CRC-EMERGENCY-OBSTRUCTION-PERFORATION, RF-CRC-FRAILTY-AGE, RF-CRC-HER2-AMP-ACTIONABLE, RF-CRC-INFECTION-SCREENING, RF-CRC-MSI-H-ACTIONABILITY, RF-CRC-RAS-MUTANT, RF-CRC-RAS-WT, RF-CRC-TRANSFORMATION-PROGRESSION

Skill catalog (0/16 activated in this plan)

All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).

Specialist	skill_id	Version	Last reviewed	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	cellular_therapy

Sources cited

SRC-ESMO-COLON-2024: ESMO CRC Clinical Practice Guideline (2024)
SRC-NCCN-COLON-2025: NCCN Colon / Rectal Cancer (v.4.2025)

Experimental options (clinical trials)

Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-05-04.

NCT	Title	Phase	Status	Sponsor	UA
NCT07361003	A Phase Ib/III Study of Suvemcitug Plus FTD/TPI in Participants With Refractory Metastatic Colorectal Cancer	PHASE3	RECRUITING	Jiangsu Simcere Pharmaceutical Co., Ltd.	—
NCT07094113	AMG 410 Alone and in Combination With Other Agents in Participants With KRAS Altered Advanced or Metastatic Solid Tumors	PHASE1	RECRUITING	Amgen	—
NCT07186842	A Clinical Trial to Test if the Investigational Drug BNT329 is Safe and Potentially Beneficial for People With Advanced Solid Tumors Known to Express the Tumor Marker CA19-9	PHASE1 / PHASE2	RECRUITING	BioNTech SE	—
NCT07353645	KRAS Neoantigen Nanovaccine as Adjuvant Therapy for Colorectal Cancer/Pancreatic Cancer	PHASE1 / PHASE2	RECRUITING	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School	—
NCT05722288	Time-Restricted Eating Versus Nutritional Counseling for the Reduction of Radiation or Chemoradiation Tx Side Effects in Patients With Prostate, Cervical, or Rectal Cancers	PHASE2	RECRUITING	City of Hope Medical Center	—
NCT07012954	ctDNA-Guided Cetuximab or Bevacizumab Plus Trifluridine/Tipiracil in RAS/BRAF Wild-Type mCRC	PHASE1 / PHASE2	RECRUITING	Sun Yat-sen University	—
NCT07229313	A Study of KIVU-107 in Participants With Locally Advanced or Metastatic Solid Tumors	PHASE1	RECRUITING	Kivu Bioscience Inc.	—
NCT06835569	A Study to Learn About Study Medicine ALTA3263 in Adults With Advanced Solid Tumors With KRAS Mutations	PHASE1	RECRUITING	Alterome Therapeutics, Inc.	—
NCT04190589	Prospective Study of Extended Robotic Right Hemicolectomy With Complete Mesocolic Excision for Cancer	NA	RECRUITING	Vejle Hospital	—
NCT07536113	Assessing the Efficacy and Safety of ctDNA-driven Selection for Anti-EGFR Retreatment in a Real World Metastatic Colorectal Cancer Patients Cohort (the REalCHALLENGE Study)	N/A	RECRUITING	Niguarda Hospital	—

Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.

Option availability in Ukraine

Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).

Option	UA registration	NSZU	Cost orientation	Access pathway
IND-CRC-ADJUVANT-STAGE2-HIGHRISK-FOLFOX — No regimen components on this track — availability unknown	— unknown	— unknown	₴-? — verify pathway	not recorded
Standard plan FOLFOX (mFOLFOX6) (REG-FOLFOX)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
IND-CRC-ADJUVANT-STAGE3-CAPOX — No regimen components on this track — availability unknown	— unknown	— unknown	₴-? — verify pathway	not recorded
Trial · NCT07361003 A Phase Ib/III Study of Suvemcitug Plus FTD/TPI in Participants With Refractory Metastatic Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07094113 AMG 410 Alone and in Combination With Other Agents in Participants With KRAS Altered Advanced or Metastatic Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07186842 A Clinical Trial to Test if the Investigational Drug BNT329 is Safe and Potentially Beneficial for People With Advanced Solid Tumors Known to Express the Tumor Marker CA19-9 No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07353645 KRAS Neoantigen Nanovaccine as Adjuvant Therapy for Colorectal Cancer/Pancreatic Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05722288 Time-Restricted Eating Versus Nutritional Counseling for the Reduction of Radiation or Chemoradiation Tx Side Effects in Patients With Prostate, Cervical, or Rectal Cancers No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07012954 ctDNA-Guided Cetuximab or Bevacizumab Plus Trifluridine/Tipiracil in RAS/BRAF Wild-Type mCRC No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07229313 A Study of KIVU-107 in Participants With Locally Advanced or Metastatic Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06835569 A Study to Learn About Study Medicine ALTA3263 in Adults With Advanced Solid Tumors With KRAS Mutations No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04190589 Prospective Study of Extended Robotic Right Hemicolectomy With Complete Mesocolic Excision for Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07536113 Assessing the Efficacy and Safety of ctDNA-driven Selection for Anti-EGFR Retreatment in a Real World Metastatic Colorectal Cancer Patients Cohort (the REalCHALLENGE Study) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.

plan_id: PLAN-BMA-KRAS_G12C_CRC-V1 | version: 1 | generated: 2026-05-04T14:13:16.628790+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.