OpenOnco · Treatment Plan

Treatment plan — Colorectal carcinoma

PLAN-VAR-CRC-RELAPSED-V1 · v1 · 2026-05-13

Patient

VAR-CRC-RELAPSED · Algorithm: ALGO-CRC-METASTATIC-2L

DiagnosisColorectal carcinoma

MOH / ICD-10C18-C20

ICD-O-38140/3; C18, C19, C20

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-MSI-STATUS	MSI-H	IA	SRC-KEYNOTE-177-ANDRE-2020 SRC-NCCN-COLON-2025 SRC-ESMO-CRC-2024 Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap.	MSI-H (microsatellite instability-high) CRC is the primary biomarker for first-line pembrolizumab monotherapy (KEYNOTE-177; mPFS 16.5 vs 8.2 mo, HR 0.60; FDA-approved 2020 for 1L mCRC MSI-H). Pembrolizumab is also FDA-approved tumor-agnostically for MSI-H/dMMR solid tumors (KEYNOTE-158, 2017). MSS/pMMR CRC does not benefit from ICI monotherapy. MSI-H (~5% of metastatic CRC) is typically detected by PCR-based fragment analysis or NGS; result correlates closely with IHC-based dMMR testing (MLH1/MSH2/MSH6/PMS2 loss). Threshold selection (MSI-H positive/negative) enforced by algorithm layer; this BMA entry surfaces ESCAT tier context only. For Lynch syndrome germline implications see BMA entries for BIO-MLH1 / BIO-MSH2 / BIO-MSH6 / BIO-PMS2.	pembrolizumab monotherapy (MSI-H 1L mCRC per SRC-KEYNOTE-177-ANDRE-2020, SRC-NCCN-COLON-2025) pembrolizumab monotherapy (tumor-agnostic MSI-H per SRC-ESMO-CRC-2024)	SRC-KEYNOTE-177-ANDRE-2020 SRC-NCCN-COLON-2025 SRC-ESMO-CRC-2024

Primary current-line option

Aggressive plan

★ DEFAULT

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

Primary current-line option per algorithm ALGO-CRC-METASTATIC-2L: selected default was filtered; promoted first remaining current-line track

Other current-line alternatives (1 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.

Aggressive plan

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

Current-line alternative presented for HCP consideration

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)	all tracks
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)	all tracks
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)	all tracks
TEST-CEA	CEA	Standard	lab	—	all tracks

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
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

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-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-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

Timeline

Treatment timeline — derived from regimen + monitoring schedule

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 · Encorafenib + Cetuximab (BEACON CRC)

28-day cycles × Until progression / unacceptable toxicity

MDT brief

Discussion questions (2, 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-BRAF-V600E
What is the status of BRAF V600E mutation (BIO-BRAF-V600E)? It is required by track(s): IND-CRC-METASTATIC-2L-BRAF-BEACON. Expected value: positive.
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 (4 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 BRAF V600E mutation (BIO-BRAF-V600E)? It is required by track(s): IND-CRC-METASTATIC-2L-BRAF-BEACON. Expected value: positive.
3	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
4	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-BRAF-V600E
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: 1/2 known (50%), 1 missing, 0 default-track gaps
Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, 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-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-BRAF-V600E`	BRAF V600E mutation	molecular_geneticist	no	IND-CRC-METASTATIC-2L-BRAF-BEACON	Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive

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	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-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
NCT06819280	Autologous Tumor-Infiltrating Lymphocyte (GT307) for Treatment of Patients With Advanced Colorectal Cancer	NA	RECRUITING	Grit Biotechnology	—	Small N (<50) Surrogate endpoint only Single country
NCT06794086	SBRT + PD-1 Monoclonal Antibody in Unresectable Colorectal Liver Metastases	PHASE3	RECRUITING	Jun Huang	—	Small N (<50) Surrogate endpoint only Single country
NCT05288205	Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation	PHASE1 / PHASE2	RECRUITING	Allist Pharmaceuticals, Inc.	—	Single country
NCT06848842	Ivonescimab Plus Chemotherapy in Patients With Initially Unresectable Colorectal Cancer Liver Metastases	PHASE2	RECRUITING	Cancer Institute and Hospital, Chinese Academy of Medical Sciences	—	Small N (<50) Surrogate endpoint only Single country
NCT07090291	China Colorectal Cancer Screening Trial 1 (C-Cost1)	NA	RECRUITING	Zhejiang University	—	Single country
NCT06167967	Circulating Tumor DNA Methylation Guiding Postoperative Adjuvant Chemotherapy in Stage III Colorectal Cancer	NA	RECRUITING	Sir Run Run Shaw Hospital	—	Single country
NCT06282445	Efficacy and Safety of Chemotherapy With XELOX (Oxaliplatin + Capecitabine) and Bevacizumab in Combination With Adebrelimab in First-line Treatment of Microsatellite Stable (MSS) Initially Unresectable Metastatic Colorectal Cancer	PHASE2	RECRUITING	The Fourth Affiliated Hospital of Zhejiang University School of Medicine	—	Small N (<50) Surrogate endpoint only Single country
NCT04693377	Cryoablation Combined With Stereotactic Body Radiation Therapy for the Treatment of Painful Bone Metastases, the CROME Trial	NA	RECRUITING	M.D. Anderson Cancer Center	—	Small N (<50) Single country
NCT07333053	Clinical Efficacy of Transarterial Infusion Chemotherapy for Unresectable Colorectal Cancer	NA	RECRUITING	Quanda Liu	—	Small N (<50) Surrogate endpoint only Single country
NCT07529301	Functional and Respiratory Predictors of Early Postoperative Outcomes	N/A	RECRUITING	Müşerref Ebru YALÇIN	—	Small N (<50) 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 Pembrolizumab monotherapy (MSI-H mCRC 1L) (REG-PEMBROLIZUMAB-MSI-MONO)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
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
Trial · NCT06819280 Autologous Tumor-Infiltrating Lymphocyte (GT307) for Treatment of Patients With Advanced Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06794086 SBRT + PD-1 Monoclonal Antibody in Unresectable Colorectal Liver Metastases No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05288205 Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06848842 Ivonescimab Plus Chemotherapy in Patients With Initially Unresectable Colorectal Cancer Liver Metastases No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07090291 China Colorectal Cancer Screening Trial 1 (C-Cost1) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06167967 Circulating Tumor DNA Methylation Guiding Postoperative Adjuvant Chemotherapy in Stage III Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06282445 Efficacy and Safety of Chemotherapy With XELOX (Oxaliplatin + Capecitabine) and Bevacizumab in Combination With Adebrelimab in First-line Treatment of Microsatellite Stable (MSS) Initially Unresectable Metastatic Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04693377 Cryoablation Combined With Stereotactic Body Radiation Therapy for the Treatment of Painful Bone Metastases, the CROME Trial No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07333053 Clinical Efficacy of Transarterial Infusion Chemotherapy for Unresectable Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07529301 Functional and Respiratory Predictors of Early Postoperative Outcomes 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.

plan_id: PLAN-VAR-CRC-RELAPSED-V1 | version: 1 | generated: 2026-05-13T10:01:51.890956+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.