OpenOnco · Treatment Plan

Treatment plan — DIS-UROTHELIAL

PLAN-BMA-FGFR3_R248C_UROTHELIAL-V1 · v1 · 2026-05-04

Patient

BMA-FGFR3_R248C_UROTHELIAL · Algorithm: ALGO-UROTHELIAL-METASTATIC-1L

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-FGFR3-MUTATION	R248C	IA	SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Sensitivity/Response) SRC-CIVIC: Level D ⚠ Resistance SRC-CIVIC: Level D (Supports, Gain of Function)	FGFR3 R248C is an extracellular-domain activating mutation included in the erdafitinib companion-diagnostic FGFR alteration panel. Treatment-equivalent to S249C: erdafitinib in 2L+ metastatic urothelial carcinoma per THOR.	erdafitinib monotherapy	SRC-NCCN-BLADDER-2025 SRC-EAU-BLADDER-2024
BIO-FGFR3-MUTATION	S249C	IA	SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Sensitivity/Response) SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Gain of Function) SRC-CIVIC: Level D ⚠ Resistance	FGFR3 S249C is the most common activating FGFR3 mutation in urothelial carcinoma. Erdafitinib is approved for FGFR3-altered metastatic urothelial carcinoma after platinum chemotherapy (THOR cohort 1, Loriot 2023 — OS benefit vs chemotherapy in 2L+).	erdafitinib monotherapy	SRC-NCCN-BLADDER-2025 SRC-EAU-BLADDER-2024
BIO-FGFR3-MUTATION	FGFR3-TACC3 fusion	IA	SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Sensitivity/Response) SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	FGFR3-TACC3 fusion is an activating rearrangement in urothelial carcinoma (~2-3%). Included in the erdafitinib companion-diagnostic FGFR alteration list. Erdafitinib responses in fusion-positive patients are comparable to those in mutation-positive (THOR, BLC2001).	erdafitinib monotherapy	SRC-NCCN-BLADDER-2025 SRC-EAU-BLADDER-2024
BIO-FGFR3-MUTATION	Y373C	IA	SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Positive) SRC-CIVIC: Level D ⚠ Resistance SRC-CIVIC: Level D (Supports, Oncogenicity)	FGFR3 Y373C is a transmembrane-domain activating mutation in urothelial carcinoma; included in erdafitinib companion-diagnostic panel. Treatment identical to other actionable FGFR3 mutations: erdafitinib 2L+ post-platinum.	erdafitinib monotherapy	SRC-NCCN-BLADDER-2025 SRC-EAU-BLADDER-2024

Treatment options (2 tracks)

Aggressive plan

★ DEFAULT

Indication

IND-UROTHELIAL-METASTATIC-1L-PLATINUM-CHEMO-AVELUMAB

Regimen

Cisplatin + gemcitabine (urothelial neoadj + metastatic)

Drugs + NSZU

Cisplatin (DRUG-CISPLATIN) 70 mg/m² IV · Day 1 of 21-day cycle · IV ⚠ NSZU — not for this indication
Gemcitabine (DRUG-GEMCITABINE) 1000 mg/m² IV · Days 1, 8 of 21-day cycle · IV ⚠ NSZU — not for this indication

Reason

Engine default per algorithm ALGO-UROTHELIAL-METASTATIC-1L: {'step': 2, 'outcome': False, 'branch': {'result': 'IND-UROTHELIAL-METASTATIC-1L-PLATINUM-CHEMO-AVELUMAB', 'notes': 'Cisplatin-ineligible + EV-pembro ineligible: gemcitabine+carboplatin (4-6 cycles) → avelumab maintenance. IND-UROTHELIAL-METASTATIC-1L-PLATINUM-CHEMO- AVELUMAB covers both cisplatin and carboplatin backbone — regimen selection guided by CrCl and patient fitness within the indication.\n'}, 'fired_red_flags': [], 'winner_red_flag': None}

Standard plan

Indication

IND-UROTHELIAL-METASTATIC-1L-EV-PEMBRO

Regimen

Enfortumab vedotin + pembrolizumab (metastatic urothelial, 1L)

Drugs + NSZU

Enfortumab vedotin (DRUG-ENFORTUMAB-VEDOTIN) 1.25 mg/kg IV · Days 1, 8 of 21-day cycle · IV ✗ Not registered in UA
Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w · Up to 2 years · IV ⚠ NSZU — not for this indication

Reason

Alternative track 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-CECT-CAP	CECT chest/abdomen/pelvis	Critical	imaging	—	all tracks

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Aggressive plan

Induction · Cisplatin + gemcitabine (uroth

21-day cycles × 4 cycles neoadj; 6 cycles metastatic

Standard plan

Induction · Enfortumab vedotin + pembroliz

21-day cycles × EV until progression; pembro up to 2 years

MDT brief

Skills (recommended) — for consideration (1)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Open questions (1, 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

Data quality

Unevaluated RedFlags: RF-UROTHELIAL-FRAILTY-AGE, RF-UROTHELIAL-HIGH-RISK-BIOLOGY, RF-UROTHELIAL-INFECTION-SCREENING, RF-UROTHELIAL-ORGAN-DYSFUNCTION, RF-UROTHELIAL-TRANSFORMATION-PROGRESSION

Skill catalog (1/16 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-EAU-BLADDER-2024: EAU Muscle-Invasive Bladder (2024)
SRC-NCCN-BLADDER-2025: NCCN Bladder Cancer (2025.v3)

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	Eligibility (excerpt)
NCT07265947	Phase 2A/B Efficacy and Safety of Dabogratinib in Participants With Low Grade Upper Tract Urothelial Carcinoma	PHASE2	RECRUITING	Tyra Biosciences, Inc	—
NCT07218380	A Study of Vepugratinib (LY3866288) in Participants With Cancer in the Urinary Tract	PHASE3	RECRUITING	Eli Lilly and Company	—

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 Cisplatin + gemcitabine (urothelial neoadj + metastatic) (REG-CISPLATIN-GEMCITABINE-UROTHELIAL)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan Enfortumab vedotin + pembrolizumab (metastatic urothelial, 1L) (REG-EV-PEMBRO-UROTHELIAL) 1/2 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Trial · NCT07265947 Phase 2A/B Efficacy and Safety of Dabogratinib in Participants With Low Grade Upper Tract Urothelial Carcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07218380 A Study of Vepugratinib (LY3866288) in Participants With Cancer in the Urinary Tract 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-FGFR3_R248C_UROTHELIAL-V1 | version: 1 | generated: 2026-05-04T14:13:16.575478+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.