OpenOnco · Treatment Plan

Treatment plan — Cholangiocarcinoma

PLAN-SHOWCASE-CHOLANGIO-IDH1-001-V1 · v1 · 2026-05-12

Patient

SHOWCASE-CHOLANGIO-IDH1-001 · Algorithm: ALGO-CHOLANGIO-2L

DiagnosisCholangiocarcinoma

MOH / ICD-10C22.1, C24.0

ICD-O-38160/3; C22.1, C24.0, C24.8

StageIV

Clinical significance of mutations (ESCAT)

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

✅ Covered biomarkers (matched in KB)

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
BIO-IDH-MUTATION	IDH1 R132 hotspot (R132C ~70%, R132L, R132G, R132H, R132S; ~13-20% of intrahepatic cholangiocarcinoma)	IA	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Better Outcome) Resistance or avoidance signal SRC-CIVIC: Level B ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	IDH1 R132 hotspot mutations occur in ~13-20% of intrahepatic cholangiocarcinoma and are FDA Level-1 actionable. Ivosidenib was FDA-approved 2021 for previously-treated IDH1-mutated locally advanced/metastatic cholangiocarcinoma based on ClarIDHy (Abou-Alfa Lancet Oncol 2020 — mPFS 2.7 vs 1.4 mo, HR 0.37; OS benefit on rank-preserving structural failure time analysis adjusted for crossover) per SRC-NCCN-HEPATOBILIARY. Comprehensive molecular profiling at diagnosis is recommended to identify IDH1-R132 patients who can be sequenced to ivosidenib in 2L after gemcitabine/cisplatin ± durvalumab (TOPAZ-1) 1L.	ivosidenib monotherapy (2L+ IDH1 R132-mutated cholangio per SRC-NCCN-HEPATOBILIARY)	SRC-NCCN-HEPATOBILIARY

⚠️ Not included in plan

Biomarker	Status
IDH1	Not in KB — ask clinician to verify
FGFR2	Excluded (negative)
MSI	Not in KB — ask clinician to verify

Primary current-line option

Aggressive plan

★ DEFAULT

Indication

IND-CHOLANGIO-2L-IDH1-IVOSIDENIB

Regimen

Ivosidenib monotherapy (ClarIDHy) — 2L+ IDH1-mutated cholangiocarcinoma

Drugs + NSZU

Ivosidenib (DRUG-IVOSIDENIB) 500 mg PO once daily, continuous · PO daily, 28-day cycle (continuous; no scheduled break) · PO ✗ Not registered in UA

Reason

Primary current-line option selected by ALGO-CHOLANGIO-2L at step 1; branch-driving red flag: RF-CHOLANGIO-IDH1-R132-ACTIONABLE.

Other current-line alternatives (2 tracks)

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

Aggressive plan

Indication

IND-CHOLANGIO-2L-HER2-ZANIDATAMAB

Regimen

Zanidatamab — 2L+ HER2-amplified biliary tract cancer (HERIZON-BTC-01)

Drugs + NSZU

Zanidatamab (DRUG-ZANIDATAMAB) 20 mg/kg · IV q2 weeks until progression / unacceptable toxicity · IV ✗ Not registered in UA

Reason

Current-line alternative presented for HCP consideration

Aggressive plan

Indication

IND-CHOLANGIO-2L-FGFR2-FUSION-PEMIGATINIB

Regimen

Pemigatinib monotherapy (FIGHT-202) — 2L+ FGFR2-fusion cholangiocarcinoma

Drugs + NSZU

Pemigatinib (DRUG-PEMIGATINIB) 13.5 mg PO once daily, 14 days on / 7 days off · PO daily, 21-day cycle (14 on / 7 off) · PO ✗ Not registered in UA

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 1 → branch IND-CHOLANGIO-2L-IDH1-IVOSIDENIB

RF-CHOLANGIO-IDH1-R132-ACTIONABLE ★ winner: IDH1 R132 mutation in intrahepatic cholangiocarcinoma after progression on gemcitabine/cisplatin-based therapy. Routes 2L targeted therapy review toward ivosidenib. SRC-FIGHT-202SRC-NCCN-HEPATOBILIARYSRC-ESMO-BTC-2023

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks

ID	Name	Priority	Category	Where to order	Needed for
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-LFT	Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)	Critical	lab	—	all tracks
TEST-ECG	Electrocardiogram	Standard	clinical_assessment	—	all tracks
TEST-NGS-COMPREHENSIVE	Comprehensive NGS tumor panel (DNA + RNA, ≥300 genes)	Desired	histology	CSD Lab: M065	desired (aggressive)

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

FGFR2 fusion or rearrangement in advanced/metastatic intrahepatic cholangiocarcinoma (~10–20% of iCCA; rare in extrahepatic / gallbladder). Treatment-defining for 2L+: pemigatinib (FIGHT-202 ORR 35.5%, mPFS 6.9 mo, mOS 21.1 mo; FDA Apr 2020) preferred when FGFR2 fusion confirmed; futibatinib (FOENIX-CCA2) covalent FGFR-TKI alternative, including some pemigatinib-resistance variants. Common partners: BICC1-FGFR2, FGFR2-AHCYL1, FGFR2-CCDC6. RF-CHOLANGIO-FGFR2-FUSION-ACTIONABLE
IDH1 R132 mutation in intrahepatic cholangiocarcinoma after progression on gemcitabine/cisplatin-based therapy. Routes 2L targeted therapy review toward ivosidenib. RF-CHOLANGIO-IDH1-R132-ACTIONABLE

CONTRA-AGGRESSIVE

Hard contraindications to escalation

What NOT to do

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

Aggressive plan (IND-CHOLANGIO-2L-IDH1-IVOSIDENIB)

Do NOT prescribe without confirmed IDH1 R132 mutation testing (tumor NGS or ctDNA) — amplification, IDH2 mutation, or non-R132 IDH1 mutations are NOT eligible.
Do NOT start without baseline ECG and correction of electrolytes (K, Mg, Ca) — QT prolongation is a class adverse effect.
Do NOT combine with strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin, St. John's wort) — ivosidenib exposure is sharply reduced.
Do NOT skip QTc monitoring (ECG at week 1, 2, 4, then monthly or as clinically indicated).
Do NOT rely on hormonal contraception as the sole method — ivosidenib induces CYP3A4; barrier contraception is required.
Do NOT confirm the plan without funding pathway — ivosidenib not registered in UA.

Aggressive plan (IND-CHOLANGIO-2L-HER2-ZANIDATAMAB)

Do NOT prescribe without confirmed HER2-amplification (IHC 3+ or IHC 2+/ISH+) — lower-level protein expression alone is insufficient for this indication.
Do NOT start without baseline echocardiogram / MUGA — HER2-targeted class toxicity includes LVEF decline.
Do NOT skip premedication for first 2-3 infusions — infusion reactions ~33%.
Do NOT ignore diarrhea prophylaxis — ~40% any-grade; patient must have loperamide at home with clear escalation plan.
Do NOT confirm the plan without funding pathway — zanidatamab not registered in UA (named-patient / EAP only).

Aggressive plan (IND-CHOLANGIO-2L-FGFR2-FUSION-PEMIGATINIB)

Do NOT prescribe without RNA-NGS (or DNA-NGS fusion-aware / FISH break-apart) confirmation of FGFR2 fusion — amplification alone is insufficient for this indication.
Do NOT start without baseline ophthalmologic exam — serous retinopathy / RPE detachment — class toxicity.
Do NOT ignore phosphate monitoring — hyperphosphatemia requires diet + sevelamer; delay / dose reduction at >7 mg/dL.
Do NOT combine with strong CYP3A4 inducers — pemigatinib exposure is sharply reduced.
Do NOT confirm the plan without funding pathway — pemigatinib not registered in UA.

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Aggressive plan

Induction · Ivosidenib monotherapy (ClarIDHy) — 2L+ IDH1-mutated cholangiocarcinoma

28-day cycles × Until progression / unacceptable toxicity

Aggressive plan

Induction · Zanidatamab — 2L+ HER2-amplified biliary tract cancer (HERIZON-BTC-01)

14-day cycles × Until progression or unacceptable toxicity

Aggressive plan

Induction · Pemigatinib monotherapy (FIGHT-202) — 2L+ FGFR2-fusion cholangiocarcinoma

21-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-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-CHOLANGIO-2L-HER2-ZANIDATAMAB. Expected value: HER2 IHC 3+ OR (IHC 2+ AND ISH amplified, HER2/CEP17 ratio ≥2.0); gastric-style scoring (Hofmann 2008 — basolateral/lateral membranous staining ≥10%).
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

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	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-CHOLANGIO-2L-HER2-ZANIDATAMAB. Expected value: HER2 IHC 3+ OR (IHC 2+ AND ISH amplified, HER2/CEP17 ratio ≥2.0); gastric-style scoring (Hofmann 2008 — basolateral/lateral membranous staining ≥10%).
3	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
4	molecular_geneticist	Specialist review	Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.

Skills (recommended) — for consideration (2)

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.

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: 2/3 known (67%), 1 missing, 0 default-track gaps
Unevaluated RedFlags: RF-CHOLANGIO-FGFR2-FUSION-ACTIONABLE, RF-CHOLANGIO-IDH1-R132-ACTIONABLE, RF-CHOLANGIOCARCINOMA-FRAILTY-AGE, RF-CHOLANGIOCARCINOMA-HIGH-RISK-BIOLOGY, RF-CHOLANGIOCARCINOMA-INFECTION-SCREENING, RF-CHOLANGIOCARCINOMA-ORGAN-DYSFUNCTION, RF-CHOLANGIOCARCINOMA-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-CHOLANGIO-2L-HER2-ZANIDATAMAB	Verify result, method, specimen, and report date before sign-off. Expected/constraint: HER2 IHC 3+ OR (IHC 2+ AND ISH amplified, HER2/CEP17 ratio ≥2.0); gastric-style scoring (Hofmann 2008 — basolateral/lateral membranous staining ≥10%)

Technical MDT skill metadata (2/16 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-CLARIDHY-ABOU-ALFA-2020: Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study (2020)
SRC-ESMO-BTC-2023: Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up (2023)
SRC-FIGHT-202: FIGHT-202 — pemigatinib in FGFR2-fusion cholangiocarcinoma (TODO: confirm citation) ()
SRC-HERIZON-BTC-01-HARDING-2023: Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study (2023)
SRC-NCCN-HEPATOBILIARY: NCCN Hepatobiliary Cancers guideline (TODO: confirm year/citation) ()

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: 2026-05-12.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT06493734	Stereotactic Body Radiation Therapy After Chemotherapy for Unresectable Perihilar Cholangiocarcinoma	NA	RECRUITING	Erasmus Medical Center	—	Small N (<50)
NCT06728410	A Phase II Study of Pemigatinib Plus Durvalumab in Previously Treated Advanced Intrahepatic Cholangiocarcinoma Patients With FGFR-2 Fusion or Rearrangement	PHASE2	RECRUITING	Mehmet Akce	—	Small N (<50) Surrogate endpoint only Single country
NCT07570849	Chidamide Combined With Chemotherapy and Immunotherapy as First-line Treatment for Advanced Intrahepatic Cholangiocarcinoma	PHASE2	RECRUITING	Shanghai Zhongshan Hospital	—	Small N (<50) Surrogate endpoint only Single country
NCT05155878	Prognostic Factors in Periampullary Tumors and Cysts	N/A	RECRUITING	Umeå University	—	Single country
NCT06298968	Combined Therapy Using Gemcitabine and Cisplatin Chemotherapy, Lenvatinib and Adebrelimab for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma	PHASE2	RECRUITING	Nanfang Hospital, Southern Medical University	—	Small N (<50) Surrogate endpoint only Single country
NCT01915225	Obtaining Solid Tumor Tissue From People Having Biopsy or Surgery for Certain Types of Cancer	N/A	RECRUITING	National Cancer Institute (NCI)	—	Single country
NCT05876754	An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma	PHASE3	RECRUITING	Servier Affaires Médicales	—	—
NCT07291947	PULSAR Combined With Immunotherapy and Chemotherapy	PHASE1 / PHASE2	RECRUITING	Wang Xin	—	Single country
NCT07224750	A Noninvasive and Screening miRNA Signature for Gastrointestinal Cancer	N/A	RECRUITING	City of Hope Medical Center	—	Single country
NCT07223307	REGULUS: MRI-guided Adaptive SABR for Liver Cancers	PHASE2	RECRUITING	Stanford University	—	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 Ivosidenib monotherapy (ClarIDHy) — 2L+ IDH1-mutated cholangiocarcinoma (REG-IVOSIDENIB-CHOLANGIO) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Aggressive plan Zanidatamab — 2L+ HER2-amplified biliary tract cancer (HERIZON-BTC-01) (REG-ZANIDATAMAB) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Aggressive plan Pemigatinib monotherapy (FIGHT-202) — 2L+ FGFR2-fusion cholangiocarcinoma (REG-PEMIGATINIB-CHOLANGIO) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Trial · NCT06493734 Stereotactic Body Radiation Therapy After Chemotherapy for Unresectable Perihilar Cholangiocarcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06728410 A Phase II Study of Pemigatinib Plus Durvalumab in Previously Treated Advanced Intrahepatic Cholangiocarcinoma Patients With FGFR-2 Fusion or Rearrangement No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07570849 Chidamide Combined With Chemotherapy and Immunotherapy as First-line Treatment for Advanced Intrahepatic Cholangiocarcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05155878 Prognostic Factors in Periampullary Tumors and Cysts No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06298968 Combined Therapy Using Gemcitabine and Cisplatin Chemotherapy, Lenvatinib and Adebrelimab for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT01915225 Obtaining Solid Tumor Tissue From People Having Biopsy or Surgery for Certain Types of Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05876754 An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07291947 PULSAR Combined With Immunotherapy and Chemotherapy No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07224750 A Noninvasive and Screening miRNA Signature for Gastrointestinal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07223307 REGULUS: MRI-guided Adaptive SABR for Liver Cancers 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: 2026-05-12.

plan_id: PLAN-SHOWCASE-CHOLANGIO-IDH1-001-V1 | version: 1 | generated: 2026-05-12T18:41:25.802966+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.