OpenOnco · Treatment Plan

Treatment plan — Cholangiocarcinoma

PLAN-VERIFIED-CHOLANGIOCARCINOMA-L2-CHOLANGIO_2L_HER2_ZANIDATAMAB-V1 · v1 · 2026-07-15

Patient

VERIFIED-CHOLANGIOCARCINOMA-L2-CHOLANGIO_2L_HER2_ZANIDATAMAB · Algorithm: ALGO-CHOLANGIO-2L

DiagnosisCholangiocarcinoma

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

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

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); ~5-15% of biliary tract cancer (higher in gallbladder + extrahepatic CCA than intrahepatic CCA)	IIA	Standard care SRC-HERIZON-BTC-01-HARDING-2023: Level B (Supports, Sensitivity/Response)	HER2-amplified biliary tract cancer (~5-15% overall; enriched in gallbladder + extrahepatic cholangiocarcinoma; ~3-5% intrahepatic CCA): zanidatamab (HER2-targeted biparatopic bispecific antibody) 20 mg/kg IV q2w produced confirmed ORR 41.3% (95% CI 30.4-52.8) in previously treated HER2 IHC 3+ or IHC 2+/ISH+ disease in HERIZON-BTC-01 (Harding et al., Lancet Oncol 2023; n=87). FDA accelerated approval November 2024 for HER2-positive (IHC 3+) BTC ≥2L. ESCAT tier IIA (FDA-approved disease-specific). NCCN category 2A. HER2 testing recommended at diagnosis for unresectable / metastatic BTC per SRC-NCCN-HEPATOBILIARY. Gastric-style scoring (Hofmann 2008 — basolateral / lateral membranous staining ≥10%) is generally applied given basolateral HER2 expression pattern in BTC.	zanidatamab monotherapy 20 mg/kg IV q2w (2L+ post gemcitabine-based 1L per SRC-NCCN-HEPATOBILIARY)	SRC-HERIZON-BTC-01-HARDING-2023 SRC-NCCN-HEPATOBILIARY SRC-ESMO-BTC-2023

Primary current-line option

Aggressive plan

★ DEFAULT

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

Primary current-line option selected by ALGO-CHOLANGIO-2L at step 2.

Other current-line alternatives (3 tracks)

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

Aggressive plan

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

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

Standard plan

Indication

IND-CHOLANGIO-ADVANCED-GEM-CIS

Regimen

Gemcitabine + cisplatin (advanced biliary tract cancer, 1L — ABC-02)

Drugs + NSZU

Gemcitabine (DRUG-GEMCITABINE) Gemcitabine 1000 mg/m² · Per regimen schedule · IV ⚠ NSZU — not for this indication
Cisplatin (DRUG-CISPLATIN) cisplatin 25 mg/m² IV d1, d8 q3w × 8 cycles · Per regimen schedule · IV ⚠ NSZU — not for this indication

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-CBC	Complete Blood Count with Differential	Critical	lab	—	aggressive
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	aggressive
TEST-CT-CHEST-ABDOMEN-PELVIS	CT chest + abdomen + pelvis with IV contrast	Critical	imaging	—	aggressive
TEST-LFT	Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)	Critical	lab	—	aggressive
TEST-ECG	Electrocardiogram	Standard	clinical_assessment	—	aggressive
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.
Detection: RNA-NGS preferred (captures fusion partners); DNA-NGS with fusion-aware caller acceptable; FISH break-apart secondary. Mandatory pre-treatment NGS in advanced iCCA (NCCN cat 1 testing). Class toxicity: hyperphosphatemia (~50%)…
RF-CHOLANGIO-FGFR2-FUSION-ACTIONABLESRC-NCCN-HEPATOBILIARYSRC-ESMO-BTC-2023SRC-FIGHT-202
IDH1 R132 mutation in intrahepatic cholangiocarcinoma after progression on gemcitabine/cisplatin-based therapy. Routes 2L targeted therapy review toward ivosidenib.
Мутація IDH1 R132 при внутрішньопечінковій холангіокарциномі після прогресування на терапії на основі гемцитабіну/цисплатину. Спрямовує розгляд таргетної терапії 2L до івосидеnoбу (FIGHT-202: загальна частота відповіді 14.8%, медіана…
RF-CHOLANGIO-IDH1-R132-ACTIONABLESRC-FIGHT-202SRC-NCCN-HEPATOBILIARYSRC-ESMO-BTC-2023

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

14-day cycles × Until progression or unacceptable toxicity

Aggressive plan

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

28-day cycles × Until progression / unacceptable toxicity

Aggressive plan

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

21-day cycles × Until progression / unacceptable toxicity

Standard plan

Induction · Gemcitabine + cisplatin (advanced biliary tract cancer, 1L — ABC-02)

21-day cycles × 6 cycles or until progression / toxicity

MDT brief

Discussion questions (3, 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-FGFR2
What is the status of FGFR2 alterations (fusion / amplification / mutation) (BIO-FGFR2)? It is required by track(s): IND-CHOLANGIO-2L-FGFR2-FUSION-PEMIGATINIB. Expected value: FGFR2 fusion or rearrangement positive (RNA-NGS preferred; DNA-NGS fusion-aware OR FISH break-apart acceptable).
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-IDH-MUTATION
What is the status of IDH1 / IDH2 mutation status (BIO-IDH-MUTATION)? It is required by track(s): IND-CHOLANGIO-2L-IDH1-IVOSIDENIB. Expected value: IDH1 R132 hotspot mutation positive (R132C / R132L / R132G / R132H / R132S; tumor NGS preferred; ctDNA acceptable when tumor tissue insufficient). IDH2 mutations NOT eligible..
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 FGFR2 alterations (fusion / amplification / mutation) (BIO-FGFR2)? It is required by track(s): IND-CHOLANGIO-2L-FGFR2-FUSION-PEMIGATINIB. Expected value: FGFR2 fusion or rearrangement positive (RNA-NGS preferred; DNA-NGS fusion-aware OR FISH break-apart acceptable).
3	molecular_geneticist	Biomarker status	What is the status of IDH1 / IDH2 mutation status (BIO-IDH-MUTATION)? It is required by track(s): IND-CHOLANGIO-2L-IDH1-IVOSIDENIB. Expected value: IDH1 R132 hotspot mutation positive (R132C / R132L / R132G / R132H / R132S; tumor NGS preferred; ctDNA acceptable when tumor tissue insufficient). IDH2 mutations NOT eligible..
4	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

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.
Owns: OQ-BIOMARKER-FGFR2, OQ-BIOMARKER-IDH-MUTATION

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: 1/3 known (33%), 2 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, RF-CLONORCHIS-CHOLANGIO-PREVENTION, RF-OPISTHORCHIS-CHOLANGIO-PREVENTION, RF-PSC-CHOLANGIOCARCINOMA-PREVENTION

Missing biomarker	Label	MDT owner	Default track	Required by	Next action
`BIO-FGFR2`	FGFR2 alterations (fusion / amplification / mutation)	molecular_geneticist	no	IND-CHOLANGIO-2L-FGFR2-FUSION-PEMIGATINIB	Verify result, method, specimen, and report date before sign-off. Expected/constraint: FGFR2 fusion or rearrangement positive (RNA-NGS preferred; DNA-NGS fusion-aware OR FISH break-apart acceptable)
`BIO-IDH-MUTATION`	IDH1 / IDH2 mutation status	molecular_geneticist	no	IND-CHOLANGIO-2L-IDH1-IVOSIDENIB	Verify result, method, specimen, and report date before sign-off. Expected/constraint: IDH1 R132 hotspot mutation positive (R132C / R132L / R132G / R132H / R132S; tumor NGS preferred; ctDNA acceptable when tumor tissue insufficient). IDH2 mutations NOT eligible.

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-CNS-2025: NCCN Central Nervous System Cancers (v.3.2025)
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: 2026-07-15.

NCT	Title	Phase	Status	Sponsor	UA	Signals	Eligibility (excerpt)
NCT05150691	A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors	PHASE1 / PHASE2	RECRUITING	DualityBio Inc.	—	Biomarker: enriched Surrogate endpoint only
NCT07334119	Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of MT-304 in Adults With Advanced HER2-Expressing Solid Tumors	PHASE1	RECRUITING	Myeloid Therapeutics	—	Biomarker: unclear Phase 1 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 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 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 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
Standard plan Gemcitabine + cisplatin (advanced biliary tract cancer, 1L — ABC-02) (REG-GEMCITABINE-CISPLATIN-CHOLANGIO)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Trial · NCT05150691 A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07334119 Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of MT-304 in Adults With Advanced HER2-Expressing 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: 2026-07-15.

plan_id: PLAN-VERIFIED-CHOLANGIOCARCINOMA-L2-CHOLANGIO_2L_HER2_ZANIDATAMAB-V1 | version: 1 | generated: 2026-07-15T13:33:22.791181+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.