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-HER2-SOLID	amplification / overexpression — IHC 3+ or (IHC 2+ + ISH amplified, HER2/CEP17 ≥2.0); ~3-5% of metastatic colorectal cancer (RAS/BRAF-WT)	IB	SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level B (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	HER2-amplified metastatic colorectal cancer (~3-5% in RAS/BRAF-WT population): tucatinib + trastuzumab is FDA-approved 2L+ for HER2- positive RAS-WT mCRC based on MOUNTAINEER (Strickler Lancet Oncol 2023 — ORR 38%, mDOR 12 mo) per SRC-NCCN-COLON-2025. Trastuzumab deruxtecan also has activity (DESTINY-CRC01 Siena Lancet Oncol 2021 — ORR 45% in HER2 IHC 3+ RAS-WT) and tumor-agnostic FDA approval (2024) for HER2-positive solid tumors that have progressed on prior therapy. Older trastuzumab + lapatinib (HERACLES) is referenced as alternative. RAS-mutant tumors should not receive HER2-directed therapy in 2L because RAS-driven resistance is well-documented per SRC-NCCN-COLON-2025.	tucatinib + trastuzumab (2L+ HER2+ RAS-WT mCRC per SRC-NCCN-COLON-2025) trastuzumab deruxtecan (2L+ HER2+ mCRC per SRC-NCCN-COLON-2025) trastuzumab + lapatinib (alternative per HERACLES, listed in SRC-NCCN-COLON-2025)	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
NCT04485013	TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers	PHASE1	RECRUITING	Tizona Therapeutics, Inc	—
NCT05514717	A Study of XMT-2056 in Advanced/Recurrent Solid Tumors That Express HER2	PHASE1	RECRUITING	Mersana Therapeutics	—
NCT04842812	Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors	PHASE1	RECRUITING	Second Affiliated Hospital of Guangzhou Medical University	—
NCT07318805	A Study to Learn About the Study Medicine Called PF-08032562 in People With Advanced or Metastatic Solid Tumors	PHASE1	RECRUITING	Pfizer	—
NCT07540572	A Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of IDE574 Therapy in Adult Participants With Advanced Solid Tumors	PHASE1 / PHASE2	RECRUITING	IDEAYA Biosciences	—
NCT05059444	ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation	N/A	RECRUITING	Guardant Health, Inc.	—
NCT06500052	A Study of BL-M17D1 in Patients With Locally Advanced or Metastatic HER2 Positive/Lower Expression Gastrointestinal Cancer and Other Solid Tumors	PHASE1	RECRUITING	Sichuan Baili Pharmaceutical Co., Ltd.	—
NCT06760819	A Study to Learn More About How Well Treatment With Sevabertinib (BAY 2927088) Tablets Works and How Safe it is in Participants Who Have a Solid Tumor With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)	PHASE2	RECRUITING	Bayer	—
NCT07192068	Clinical Trial Evaluating the Activity of Zanidatamab for the Treatment of Patients With Solid Tumors With an Alteration of the HER2 Gene.	PHASE2	RECRUITING	UNICANCER	—
NCT06625775	Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors	PHASE1	RECRUITING	TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)	—

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 · NCT04485013 TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05514717 A Study of XMT-2056 in Advanced/Recurrent Solid Tumors That Express HER2 No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04842812 Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07318805 A Study to Learn About the Study Medicine Called PF-08032562 in People With Advanced or Metastatic Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07540572 A Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of IDE574 Therapy in Adult Participants With Advanced Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05059444 ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06500052 A Study of BL-M17D1 in Patients With Locally Advanced or Metastatic HER2 Positive/Lower Expression Gastrointestinal Cancer and Other Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06760819 A Study to Learn More About How Well Treatment With Sevabertinib (BAY 2927088) Tablets Works and How Safe it is in Participants Who Have a Solid Tumor With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07192068 Clinical Trial Evaluating the Activity of Zanidatamab for the Treatment of Patients With Solid Tumors With an Alteration of the HER2 Gene. No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06625775 Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors 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-HER2_AMP_CRC-V1 | version: 1 | generated: 2026-05-04T14:13:16.612972+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.