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-CSF1R	CSF1R pathway activation — diffuse-type TGCT (COL6A3-CSF1 fusion OR CSF1 overexpression; pexidartinib indication does not require molecular confirmation of fusion)	IA	SRC-ILLUMINATE-TAP-2019: Level A (Supports, Sensitivity/Response) SRC-NCCN-SARCOMA: Level Category 1 (Supports, Sensitivity/Response) SRC-ESMO-SARCOMA-2024: Level A (Supports, Sensitivity/Response)	Pexidartinib (PLX3397), a CSF1R/KIT/FLT3 inhibitor, is FDA-approved (August 2019) for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations not amenable to improvement with surgery. ILLUMINATE phase III trial (Tap et al., Lancet 2019): N=120 (pexidartinib vs placebo, crossover design); primary endpoint ORR at week 25 by RECIST 1.1 and TTP-MRI. ORR: 38% (RECIST) vs 0% placebo (p<0.0001); 56% by TTP-MRI vs 0%. mDOR: not reached at median 23.1 months follow-up. Clinical benefit rate: 56%. Safety: significant hepatotoxicity (cholestatic hepatitis, including one fatal case in open-label extension); ALT/AST elevations in ~51%; FDA REMS program mandatory. EMA approved for same indication (2020). No biomarker companion diagnostic required — all TGCT patients are eligible based on clinical criteria (symptomatic, surgery-resistant). CSF1R IHC or COL6A3-CSF1 fusion testing is not required for treatment initiation.	pexidartinib 400 mg PO BID (with food; REMS enrollment required; baseline LFTs, monthly monitoring for first 8 weeks, then every 3 months)	SRC-ILLUMINATE-TAP-2019 SRC-NCCN-SARCOMA SRC-ESMO-SARCOMA-2024

Treatment options (1 tracks)

Standard plan

★ DEFAULT

Indication

IND-TGCT-1L-PEXIDARTINIB

Regimen

Pexidartinib monotherapy (symptomatic TGCT — diffuse-type)

Drugs + NSZU

Pexidartinib (DRUG-PEXIDARTINIB) 400 mg PO twice daily with a high-fat meal for first 2 weeks, then 800 mg/day total (consult current prescribing info) · Continuous until progression or unacceptable toxicity; available through REMS only · PO ✗ Not registered in UA

Reason

Engine default per algorithm ALGO-TGCT-1L: {'step': 1, 'outcome': False, 'branch': {'result': 'IND-TGCT-1L-PEXIDARTINIB'}, 'fired_red_flags': [], 'winner_red_flag': None}

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-LFT	Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)	Critical	lab	—	all tracks

What NOT to do

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

Standard plan (IND-TGCT-1L-PEXIDARTINIB)

Do NOT prescribe with hepatic impairment (AST/ALT >3× ULN) — absolute contraindication
Do NOT skip mandatory weekly LFT monitoring ×8 weeks (REMS requirement)
Do NOT co-administer with other hepatotoxic agents
Do NOT prescribe without confirmed REMS/compassionate-use access
Do NOT prescribe if surgery can still improve joint function — pexidartinib for unimprovable cases only

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Pexidartinib monotherapy (symp

28-day cycles × Continuous until progression

MDT brief

Skill catalog (0/16 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-SARCOMA-2024: ESMO soft-tissue sarcoma guideline (2024) (TODO: confirm citation) ()
SRC-ILLUMINATE-TAP-2019: ILLUMINATE: Pexidartinib vs Placebo in Tenosynovial Giant Cell Tumor (Tap et al., Lancet 2019) ()

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)
NCT07499362	Study of Pimicotinib in Japanese Participants With Tenosynovial Giant Cell Tumor (TGCT) (J-MANEUVER)	PHASE2	RECRUITING	Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany	—

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
Standard plan Pexidartinib monotherapy (symptomatic TGCT — diffuse-type) (REG-PEXIDARTINIB-TGCT) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Trial · NCT07499362 Study of Pimicotinib in Japanese Participants With Tenosynovial Giant Cell Tumor (TGCT) (J-MANEUVER) 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-CSF1R_TGCT-V1 | version: 1 | generated: 2026-05-04T14:13:16.583171+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.