Patient
SHOWCASE-CRC-BRAF-001 · Algorithm: ALGO-CRC-METASTATIC-2L
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-BRAF-V600E | V600E | IB | Molecular evidence option - SRC-CIVIC: Level A (Supports, Sensitivity/Response)
- SRC-CIVIC: Level B (Supports, Poor Outcome)
Resistance or avoidance signal Trial or research option - SRC-CIVIC: Level C (Supports, Sensitivity/Response)
- SRC-CIVIC: Level D (Supports, Sensitivity/Response)
| BRAF V600E in metastatic CRC: encorafenib + cetuximab (with or without binimetinib) improves OS vs cetuximab+irinotecan in 2L+ (BEACON-CRC, Kopetz et al. 2019). BRAFi monotherapy is ineffective in CRC due to EGFR-mediated feedback reactivation — distinct from melanoma where BRAFi alone works. | encorafenib + cetuximab
encorafenib + cetuximab + binimetinib (off-label triplet) | - SRC-NCCN-COLON-2025
- SRC-ESMO-COLON-2024
|
| Biomarker | Status |
|---|
| MSI | Not in KB — ask clinician to verify |
| BIO-MSI-STATUS | BIO definition in KB; no ESCAT BMA entry — verify with clinician |
| RAS | Excluded (negative) |
Primary current-line option
- Indication
- IND-CRC-METASTATIC-2L-BRAF-BEACON
- Regimen
- Encorafenib + Cetuximab (BEACON CRC)
- Drugs + NSZU
- Encorafenib (DRUG-ENCORAFENIB) 300 mg PO daily continuous · Continuous · PO ⚠ Out-of-pocket
- Cetuximab (DRUG-CETUXIMAB) 400 mg/m² IV loading then 250 mg/m² weekly · IV weekly · IV ✓ NSZU covered
- Reason
- Primary current-line option selected by ALGO-CRC-METASTATIC-2L at step 2; branch-driving red flag: RF-CRC-BRAF-V600E-POOR-PROGNOSIS.
Other current-line alternatives (6 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-CRC-METASTATIC-2L-MSI-H-PEMBRO
- Regimen
- Pembrolizumab monotherapy (MSI-H mCRC 1L)
- Drugs + NSZU
- Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w OR 400 mg IV q6w · Until progression / unacceptable toxicity / 35 cycles (about 2 years) · IV ⚠ NSZU — not for this indication
- Hard contraindications
- CI-PEMBROLIZUMAB-AUTOIMMUNE
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CRC-METASTATIC-2L-KRAS-G12C-SOTORASIB-CETUXIMAB
- Regimen
- Sotorasib + Cetuximab (CodeBreaK 300, KRAS G12C+ mCRC)
- Drugs + NSZU
- Sotorasib (DRUG-SOTORASIB) 960 mg PO once daily continuous · Continuous · PO ✗ Not registered in UA
- Cetuximab (DRUG-CETUXIMAB) 500 mg/m² IV q2w (preferred) OR 400 mg/m² loading then 250 mg/m² weekly · IV q2w · IV ✓ NSZU covered
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CRC-METASTATIC-2L-HER2-AMP-TUCATINIB
- Regimen
- Tucatinib + Trastuzumab (MOUNTAINEER, HER2+ RAS-WT mCRC)
- Drugs + NSZU
- Tucatinib (DRUG-TUCATINIB) 300 mg PO BID continuous · Continuous · PO ✗ Not registered in UA
- Trastuzumab (DRUG-TRASTUZUMAB) 8 mg/kg IV loading then 6 mg/kg IV q3w · IV q3w · IV ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CRC-METASTATIC-2L-HER2-AMP-T-DXD
- Regimen
- Trastuzumab-deruxtecan monotherapy (DESTINY-CRC01, HER2+ mCRC)
- Drugs + NSZU
- Trastuzumab deruxtecan (T-DXd) (DRUG-TRASTUZUMAB-DERUXTECAN) 6.4 mg/kg IV q3w · IV q3w (DESTINY-CRC01 dosing; lower than 5.4 mg/kg breast/gastric dose for ILD risk balance) · IV ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CRC-METASTATIC-2L-EGFRI-RECHALLENGE
- Regimen
- FOLFOX + Cetuximab
- Drugs + NSZU
- Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² · IV day 1 · IV ✓ NSZU covered
- Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² · IV day 1 · 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
- Cetuximab (DRUG-CETUXIMAB) 500 mg/m² q2w (preferred for FOLFOX schedule; alternatively 400 mg/m² loading then 250 mg/m² weekly) · IV day 1 of each 14-d cycle · IV ✓ NSZU covered
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CRC-METASTATIC-2L-FOLFIRI-BEV
- Regimen
- FOLFIRI + Bevacizumab (or ± cetuximab if RAS-WT left-sided)
- Drugs + NSZU
- Irinotecan (DRUG-IRINOTECAN) 180 mg/m² · IV day 1 of each 14-day cycle · IV ✓ NSZU covered
- Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² · IV day 1 · 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
- Bevacizumab (DRUG-BEVACIZUMAB) 5 mg/kg (FOLFIRI-bev variant) · IV day 1 of each 14-day cycle · IV ✓ NSZU covered
- Supportive care
- SUP-GCSF-NEUTROPENIA
- Reason
- Current-line alternative presented for HCP consideration
Why this branch was chosen
Triggers from the patient profile that fired and drove the chosen branch.
Step 2 → branch IND-CRC-METASTATIC-2L-BRAF-BEACON
- RF-CRC-BRAF-V600E-POOR-PROGNOSIS ★ winner: BRAF V600E mutation in mCRC: ~8-10% prevalence, poor prognosis (median OS halved vs BRAF-WT on standard chemo). Cetuximab/panitumumab ineffective. Encorafenib + cetuximab (BEACON CRC) is preferred 2L+; some 1L data favor FOLFOXIRI + bev intensification in MSS BRAF-mutant.
SRC-NCCN-COLON-2025SRC-ESMO-COLON-2024
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-BRAF-V600E | BRAF V600E mutation testing | Critical | histology | CSD Lab ✓ (code TBC) | aggressive |
| TEST-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | all tracks |
| TEST-CT-CHEST-ABDOMEN-PELVIS | CT chest + abdomen + pelvis with IV contrast | Critical | imaging | — | all tracks |
| TEST-DMMR-IHC | MMR proteins IHC (MLH1 / MSH2 / MSH6 / PMS2) | Critical | histology | CSD Lab ✓ (code TBC) | aggressive |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | all tracks |
| TEST-MSI-PCR-OR-NGS | MSI status by PCR or NGS | Critical | histology | CSD Lab: M065
CSD Lab ✓ (code TBC) | aggressive |
| TEST-RAS-EXTENDED | RAS extended panel (KRAS exons 2-4 + NRAS exons 2-4) | Critical | histology | CSD Lab: M065 | all tracks |
| TEST-CEA | CEA | Standard | lab | — | all tracks |
| TEST-ECHO | Echocardiography | Standard | imaging | — | aggressive |
| TEST-HER2-IHC-ISH-IF-RAS-WT | HER2 IHC + reflex ISH (gastric scoring criteria) | Standard | histology | CSD Lab ✓ (code TBC) | aggressive |
| TEST-NGS-COMPREHENSIVE | Comprehensive NGS tumor panel (DNA + RNA, ≥300 genes) | Desired | histology | CSD Lab: M065 | aggressive |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- BRAF V600E mutation in mCRC: ~8-10% prevalence, poor prognosis (median OS halved vs BRAF-WT on standard chemo). Cetuximab/panitumumab ineffective. Encorafenib + cetuximab (BEACON CRC) is preferred 2L+; some 1L data favor FOLFOXIRI + bev intensification in MSS BRAF-mutant.
RF-CRC-BRAF-V600E-POOR-PROGNOSIS
- Surgical emergency in CRC: complete bowel obstruction (closed-loop or large-bowel obstruction with competent ileocecal valve), perforation with peritonitis, or massive lower-GI bleed requiring transfusion. Mandates urgent surgery / interventional decompression BEFORE any systemic therapy decision; staging and biomarker work-up are deferred until patient is stabilized.
RF-CRC-EMERGENCY-OBSTRUCTION-PERFORATION
- 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
- HER2 amplification in metastatic colorectal cancer — IHC 3+ OR (IHC 2+ AND ISH amplified, HER2/CEP17 ≥2.0). Present in ~3% of mCRC, enriched in left-sided RAS-WT tumors. Treatment-defining for RAS-WT subset: tucatinib + trastuzumab (MOUNTAINEER ORR 38%, mPFS 8.2 mo, mOS 24.1 mo; FDA Jan 2023) as 2L+/3L+ standard; T-DXd (DESTINY-CRC01) as alternative for IHC 3+ heavily pretreated. Excludes RAS-mutant (MOUNTAINEER eligibility) and MSI-H (pembrolizumab supersedes). Distinct from BIO-HER2-SOLID composite IHC marker: this red-flag is the actionability gate that fires for the CRC HER2-amp + RAS-WT subset specifically.
RF-CRC-HER2-AMP-ACTIONABLE
- MSI-high / dMMR mCRC — treatment-defining biomarker. KEYNOTE-177 established pembrolizumab 1L over FOLFOX+bev (PFS 16.5 vs 8.2 mo). This RF intensifies toward the immunotherapy track and overrides the default RAS/BRAF-driven chemo algorithm.
RF-CRC-MSI-H-ACTIONABILITY
- Metastatic colorectal cancer with RAS wild-type status: KRAS exon 2 (codons 12, 13), exon 3 (codons 59, 61), exon 4 (codons 117, 146) AND NRAS exon 2/3/4 ALL wild-type by NGS or extended-RAS PCR. Defines the ~50% of mCRC eligible for anti-EGFR monoclonal antibody therapy (cetuximab, panitumumab) when combined with chemotherapy backbone. Left-sided RAS-WT mCRC particularly benefits from 1L anti-EGFR + FOLFOX/ FOLFIRI (CALGB/SWOG-80405, FIRE-3, PRIME, CRYSTAL — survival benefit driven by left-sided primaries; right-sided RAS-WT does NOT benefit and routes to bevacizumab + chemo).
RF-CRC-RAS-WT
CONTRA-AGGRESSIVE
Hard contraindications to escalation
- Pembrolizumab (and other PD-1/PD-L1 inhibitors) augment T-cell responses; in patients with active autoimmunity or post-transplant immunosuppression, this can precipitate severe organ-specific flares (colitis, hepatitis, pneumonitis, transplant rejection) that may be fatal or require transplant loss.
CI-PEMBROLIZUMAB-AUTOIMMUNE
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-CRC-METASTATIC-2L-BRAF-BEACON)
- Do NOT use anti-EGFR (cetuximab/panitumumab) MONOTHERAPY in BRAF V600E — minimal benefit (BEACON control arm performance)
- Do NOT skip skin dermatology surveillance (BRAFi class effect — new SCC + melanoma risk)
- Do NOT continue through QTcF >500 ms without dose hold + ECG
Aggressive plan (IND-CRC-METASTATIC-2L-MSI-H-PEMBRO)
- Do NOT prescribe without verified MSI-H/dMMR status — false-positive MSI may cause hyperprogression.
- Do NOT continue pembrolizumab through Grade 3+ irAE without specialist consultation + steroid taper.
- Do NOT combine with chronic high-dose corticosteroids — pharmacodynamic blunting of ICI.
- Do NOT prescribe in active autoimmune disease without rheumatology / endocrinology MDT.
- Do NOT discontinue therapy at tumor pseudoprogression (early flare-up imaging) without biopsy / iRECIST evaluation.
- Do NOT confirm the plan without funding pathway — pembrolizumab not NSZU-reimbursed for CRC.
Aggressive plan (IND-CRC-METASTATIC-2L-KRAS-G12C-SOTORASIB-CETUXIMAB)
- Do NOT prescribe without verified KRAS G12C status — other KRAS variants (G12D, G12V, G13D) do not respond.
- Do NOT use sotorasib in combination with PPI — significantly reduces absorption (acid-dependent dissolution).
- Do NOT initiate without baseline LFTs — sotorasib hepatotoxicity ~25% transaminase elevation.
- Do NOT combine with strong CYP3A4 inducers — sotorasib levels reduced.
- Do NOT ignore acneiform rash management — cetuximab requires tetracycline + topical clindamycin protocol.
- Do NOT continue sotorasib with Grade 3+ hepatic AE — hold + reduce dose or discontinue.
- Do NOT confirm the plan without funding pathway — sotorasib not registered in UA; cetuximab not reimbursed for RAS-mut.
Aggressive plan (IND-CRC-METASTATIC-2L-HER2-AMP-TUCATINIB)
- Do NOT prescribe in RAS-mutant patients — MOUNTAINEER excluded RAS-mut; benefit substantially reduced.
- Do NOT initiate without baseline LVEF — trastuzumab cardiotoxicity surveillance protocol mandatory (q3 mo).
- Do NOT ignore early diarrhea management — tucatinib loperamide protocol; reduce dose if Grade ≥3.
- Do NOT combine with strong CYP3A4 inducers — tucatinib levels reduced significantly.
- Do NOT continue with LVEF drop ≥10% absolute OR LVEF <50% — hold trastuzumab; cardiology consult.
- Do NOT confirm the plan without funding pathway — tucatinib not registered in UA.
Aggressive plan (IND-CRC-METASTATIC-2L-HER2-AMP-T-DXD)
- Do NOT prescribe in baseline ILD/pneumonitis OR prior amiodarone-induced lung disease — high re-activation risk.
- Do NOT ignore new respiratory symptoms (cough, dyspnea) — STOP T-DXd, urgent CT, low-threshold steroids.
- Do NOT prescribe in RAS-mutant patients — DESTINY-CRC01 excluded RAS-mut.
- Do NOT initiate without baseline LVEF — trastuzumab moiety cardiotoxicity surveillance.
- Do NOT combine with other DNA topo-I inhibitors (irinotecan, topotecan) — overlapping toxicity.
- Do NOT continue with Grade 2+ pneumonitis — permanently discontinue T-DXd.
- Do NOT confirm the plan without funding pathway — T-DXd not NSZU-reimbursed for CRC.
Aggressive plan (IND-CRC-METASTATIC-2L-EGFRI-RECHALLENGE)
- Do NOT prescribe rechallenge without prior anti-EGFR response (PR+ OR SD ≥6 mo) — inadequate selection.
- Do NOT use rechallenge immediately after prior anti-EGFR (without intervening line) — clonal selection has not yet decayed.
- Do NOT ignore RAS-WT confirmation — baseline RAS-mut patients should not receive rechallenge.
- Do NOT initiate in known BRAF V600E — preferred encorafenib + cetuximab (BEACON).
- Do NOT ignore acneiform rash management — tetracycline + topical clindamycin protocol.
- Do NOT confirm rechallenge without funding pathway — cetuximab not NSZU-reimbursed for non-1L.
Standard plan (IND-CRC-METASTATIC-2L-FOLFIRI-BEV)
- Do NOT use anti-EGFR in RAS-mutant patients — minimal benefit + potential harmful effect.
- Do NOT initiate within 28 days of major surgery — bevacizumab perforation/dehiscence risk.
- Do NOT continue bevacizumab in uncontrolled HTN >160/100 — cerebrovascular risk.
- Do NOT ignore UGT1A1 testing if available — *28/*28 risk of severe neutropenia + diarrhea.
- Do NOT skip the loperamide protocol for irinotecan-induced delayed diarrhea — fatal dehydration possible.
- Do NOT use in high-risk varices / active hemoptysis (bevacizumab).
- Do NOT confirm anti-EGFR without funding — cetuximab / panitumumab not reimbursed for 2L.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Induction · Encorafenib + Cetuximab (BEACON CRC)
28-day cycles × Until progression / unacceptable toxicity
Aggressive plan
Induction · Pembrolizumab monotherapy (MSI-H mCRC 1L)
21-day cycles × Until progression / unacceptable toxicity / max 35 cycles per KEYNOTE-177
Aggressive plan
Induction · Sotorasib + Cetuximab (CodeBreaK 300, KRAS G12C+ mCRC)
14-day cycles × Until progression / unacceptable toxicity
Aggressive plan
Induction · Tucatinib + Trastuzumab (MOUNTAINEER, HER2+ RAS-WT mCRC)
21-day cycles × Until progression / unacceptable toxicity
Aggressive plan
Induction · Trastuzumab-deruxtecan monotherapy (DESTINY-CRC01, HER2+ mCRC)
21-day cycles × Until progression / unacceptable toxicity / ILD
Aggressive plan
Induction · FOLFOX + Cetuximab
14-day cycles × Until progression / unacceptable toxicity
Standard plan
Induction · FOLFIRI + Bevacizumab (or ± cetuximab if RAS-WT left-sided)
14-day cycles × Until progression / unacceptable toxicity (mCRC 2L+)
MDT brief
Discussion questions (4, 0 blocking)
OQ-LDH-CURRENT
What is the current LDH? Marker of tumor burden and transformation.
LDH is part of the prognostic indices of indolent lymphomas.
→ hematologist
OQ-BIOMARKER-HER2-SOLID
What is the status of HER2 status (solid tumors — gastric/GEJ/CRC scoring) (BIO-HER2-SOLID)? It is required by track(s): IND-CRC-METASTATIC-2L-HER2-AMP-TUCATINIB, IND-CRC-METASTATIC-2L-HER2-AMP-T-DXD. Expected value: amplified — IHC 3+ OR (IHC 2+ AND ISH+).
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ pathologist
OQ-BIOMARKER-KRAS-G12C
What is the status of KRAS G12C mutation (BIO-KRAS-G12C)? It is required by track(s): IND-CRC-METASTATIC-2L-KRAS-G12C-SOTORASIB-CETUXIMAB. Expected value: G12C-positive (covalent inhibitor target).
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ molecular_geneticist
OQ-BIOMARKER-RAS-MUTATION
What is the status of RAS mutation status (KRAS / NRAS exons 2-4) (BIO-RAS-MUTATION)? It is required by track(s): IND-CRC-METASTATIC-2L-EGFRI-RECHALLENGE. Expected value: RAS wild-type at baseline AND (preferably) RAS-WT confirmed on ctDNA at rechallenge timepoint (CHRONOS biomarker selection).
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ molecular_geneticist
MDT talk tree (6 steps)
| # | Owner | Topic | Action |
|---|
| 1 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 2 | molecular_geneticist | Biomarker status | What is the status of KRAS G12C mutation (BIO-KRAS-G12C)? It is required by track(s): IND-CRC-METASTATIC-2L-KRAS-G12C-SOTORASIB-CETUXIMAB. Expected value: G12C-positive (covalent inhibitor target). |
| 3 | molecular_geneticist | Biomarker status | What is the status of RAS mutation status (KRAS / NRAS exons 2-4) (BIO-RAS-MUTATION)? It is required by track(s): IND-CRC-METASTATIC-2L-EGFRI-RECHALLENGE. Expected value: RAS wild-type at baseline AND (preferably) RAS-WT confirmed on ctDNA at rechallenge timepoint (CHRONOS biomarker selection). |
| 4 | pathologist | Biomarker status | What is the status of HER2 status (solid tumors — gastric/GEJ/CRC scoring) (BIO-HER2-SOLID)? It is required by track(s): IND-CRC-METASTATIC-2L-HER2-AMP-TUCATINIB, IND-CRC-METASTATIC-2L-HER2-AMP-T-DXD. Expected value: amplified — IHC 3+ OR (IHC 2+ AND ISH+). |
| 5 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
| 6 | social_worker_case_manager | Specialist review | Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed. |
Skills (recommended) — for consideration (3)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
- Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
Owns: OQ-BIOMARKER-KRAS-G12C, OQ-BIOMARKER-RAS-MUTATION
- Social worker / case manager recommended
Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed.
Data quality
Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.
- Biomarker coverage: 2/5 known (40%), 3 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, 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-OLIGOMET-LIVER-DEFINITION, RF-CRC-RAS-MUTANT, RF-CRC-RAS-WT, RF-CRC-TRANSFORMATION-PROGRESSION
| Missing biomarker | Label | MDT owner | Default track | Required by | Next action |
|---|
BIO-HER2-SOLID | HER2 status (solid tumors — gastric/GEJ/CRC scoring) | pathologist | no | IND-CRC-METASTATIC-2L-HER2-AMP-TUCATINIB, IND-CRC-METASTATIC-2L-HER2-AMP-T-DXD | Verify result, method, specimen, and report date before sign-off. Expected/constraint: amplified — IHC 3+ OR (IHC 2+ AND ISH+) |
BIO-KRAS-G12C | KRAS G12C mutation | molecular_geneticist | no | IND-CRC-METASTATIC-2L-KRAS-G12C-SOTORASIB-CETUXIMAB | Verify result, method, specimen, and report date before sign-off. Expected/constraint: G12C-positive (covalent inhibitor target) |
BIO-RAS-MUTATION | RAS mutation status (KRAS / NRAS exons 2-4) | molecular_geneticist | no | IND-CRC-METASTATIC-2L-EGFRI-RECHALLENGE | Verify result, method, specimen, and report date before sign-off. Expected/constraint: RAS wild-type at baseline AND (preferably) RAS-WT confirmed on ctDNA at rechallenge timepoint (CHRONOS biomarker selection) |
Technical MDT skill metadata (3/16 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 | Sign-offs | Domain |
|---|
| Cellular therapy specialist (CAR-T) | cellular_therapy_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| Clinical pharmacist | clinical_pharmacist | v0.1.0 | 2026-04-25 | 0 | clinical_pharmacy |
| Hematologist / oncohematologist | hematologist | v0.1.0 | 2026-04-25 | 0 | hematology_oncology |
| Hematopathologist (lymphoma / leukemia / myeloma) | hematopathologist | v0.1.0 | 2026-04-25 | 0 | hematopathology |
| Infectious disease / hepatology | infectious_disease_hepatology | v0.1.0 | 2026-04-25 | 0 | infectious_diseases |
| Medical oncologist (solid-tumor chemotherapist) | medical_oncologist | v0.1.0 | 2026-04-25 | 0 | solid_oncology |
| Molecular geneticist / molecular oncologist | molecular_geneticist | v0.1.0 | 2026-04-25 | 0 | molecular_oncology |
| Palliative care | palliative_care | v0.1.0 | 2026-04-25 | 0 | palliative_care |
| Pathologist (general) | pathologist | v0.1.0 | 2026-04-25 | 0 | pathology |
| Primary care / family physician | primary_care | v0.1.0 | 2026-04-25 | 0 | primary_care |
| Psycho-oncologist | psychologist | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Radiation oncologist | radiation_oncologist | v0.1.0 | 2026-04-25 | 0 | radiation_oncology |
| Radiologist | radiologist | v0.1.0 | 2026-04-25 | 0 | diagnostic_imaging |
| Social worker / case manager | social_worker_case_manager | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Surgical oncologist | surgical_oncologist | v0.1.0 | 2026-04-25 | 0 | surgical_oncology |
| Transplant specialist (BMT) | transplant_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
Sources cited
- SRC-DESTINY-CRC01-SIENA-2021: Trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial (2021)
- SRC-ESMO-COLON-2024: ESMO CRC Clinical Practice Guideline (2024)
- SRC-KEYNOTE-164-LE-2020: Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer (KEYNOTE-164) (2020)
- SRC-KEYNOTE-177-ANDRE-2020: Pembrolizumab versus Chemotherapy for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer (2020)
- 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: 2026-05-13.
| NCT | Title | Phase | Status | Sponsor | UA | Signals | Eligibility (excerpt) |
|---|
| NCT06603376 | Irinotecan Hydrochloride Liposome Injection (Ⅱ) Combined with Fluorouracil, Folinic Acid, Vermofenib and Cetuximab in First-line Treatment of BRAFV600E Mutated Advanced Colorectal Cancer | PHASE2 | RECRUITING | — | Biomarker: enriched Surrogate endpoint only Single country | |
| NCT06640166 | Encorafenib + Cetuximab Beyond Progression in Combination With FOLFIRI in Patients With BRAF V600E Mutated Metastatic Colorectal Cancer Progressing on Encorafenib + Cetuximab. | PHASE2 | RECRUITING | — | Biomarker: enriched Small N (<50) Surrogate endpoint only Single country | |
| NCT05985109 | KN 046 Plus Regorafenib in MSS Metastatic Colorectal Cancer | PHASE2 | RECRUITING | — | Surrogate endpoint only Single country | |
| NCT07506109 | A Phase II Study of Sintilimab Combined With Ipilimumab N01, Cetuximab and Dabrafenib in Patients With Microsatellite-Stable, BRAF V600E-Mutated Metastatic Colorectal Cancer | PHASE2 | RECRUITING | — | Biomarker: enriched Small N (<50) Surrogate endpoint only Single country | |
| NCT06008119 | Efficacy and Safety of Tunlametinib Plus Vemurafenib in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer | PHASE3 | RECRUITING | — | Biomarker: enriched Surrogate endpoint only Single country | |
| NCT06207656 | Study to Evaluate the Efficacy and Safety of Cetuximab in Combination with Encorafenib Plus Binimetinib As Induction Treatment in BRAF V600E Mutated MSS Initially Resectable or Potentially Resectable Advanced Colorectal Cancer | PHASE2 | RECRUITING | — | Biomarker: enriched Single country | |
| NCT06763029 | Irinotecan Liposomes Combined with Cetuximab + Vermofenib in First-line Failure of Advanced Colorectal Cancer | PHASE2 | RECRUITING | — | Biomarker: enriched Small N (<50) Surrogate endpoint only Single country | |
| NCT07150247 | Safety and Efficacy of IB-FOLFIRI in BRAF V600E-Mutant Metastatic Colorectal Cancer | PHASE2 | RECRUITING | — | Biomarker: enriched Small N (<50) Surrogate endpoint only Single country | |
| NCT06978400 | A Study of Dabrafenib Plus Cetuximab/Panitumumab With FOLFOX in the First Line of Therapy in People With Metastatic Colorectal Cancer | PHASE2 | RECRUITING | — | Biomarker: enriched Surrogate endpoint only Single country | |
| NCT06411600 | Combination Therapy for BRAF-V600E Metastatic CRCm | PHASE2 | RECRUITING | — | Biomarker: enriched Surrogate endpoint only Single country | |
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 |
|---|
| Aggressive plan Encorafenib + Cetuximab (BEACON CRC) (REG-ENCORAFENIB-CETUXIMAB) 1/2 component drug(s) not on NSZU formulary | ✓ registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Pembrolizumab monotherapy (MSI-H mCRC 1L) (REG-PEMBROLIZUMAB-MSI-MONO) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Sotorasib + Cetuximab (CodeBreaK 300, KRAS G12C+ mCRC) (REG-SOTORASIB-CETUXIMAB-CRC) 1/2 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Tucatinib + Trastuzumab (MOUNTAINEER, HER2+ RAS-WT mCRC) (REG-TUCATINIB-TRASTUZUMAB-CRC) 1/2 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Trastuzumab-deruxtecan monotherapy (DESTINY-CRC01, HER2+ mCRC) (REG-TRASTUZUMAB-DERUXTECAN-CRC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan FOLFOX + Cetuximab (REG-FOLFOX-CETUX) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan FOLFIRI + Bevacizumab (or ± cetuximab if RAS-WT left-sided) (REG-FOLFIRI-BEV) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Trial · NCT06603376 Irinotecan Hydrochloride Liposome Injection (Ⅱ) Combined with Fluorouracil, Folinic Acid, Vermofenib and Cetuximab in First-line Treatment of BRAFV600E Mutated Advanced Colorectal Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06640166 Encorafenib + Cetuximab Beyond Progression in Combination With FOLFIRI in Patients With BRAF V600E Mutated Metastatic Colorectal Cancer Progressing on Encorafenib + Cetuximab. No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT05985109 KN 046 Plus Regorafenib in MSS Metastatic Colorectal Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07506109 A Phase II Study of Sintilimab Combined With Ipilimumab N01, Cetuximab and Dabrafenib in Patients With Microsatellite-Stable, BRAF V600E-Mutated Metastatic Colorectal Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06008119 Efficacy and Safety of Tunlametinib Plus Vemurafenib in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06207656 Study to Evaluate the Efficacy and Safety of Cetuximab in Combination with Encorafenib Plus Binimetinib As Induction Treatment in BRAF V600E Mutated MSS Initially Resectable or Potentially Resectable Advanced Colorectal Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06763029 Irinotecan Liposomes Combined with Cetuximab + Vermofenib in First-line Failure of Advanced Colorectal Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07150247 Safety and Efficacy of IB-FOLFIRI in BRAF V600E-Mutant Metastatic Colorectal Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06978400 A Study of Dabrafenib Plus Cetuximab/Panitumumab With FOLFOX in the First Line of Therapy in People With Metastatic Colorectal Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06411600 Combination Therapy for BRAF-V600E Metastatic CRCm 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: 2026-05-13.