OpenOnco · Treatment Plan

Treatment plan — DIS-GIST

PLAN-BMA-KIT_D816V_GIST-V1 · v1 · 2026-05-04

Patient

BMA-KIT_D816V_GIST · Algorithm: ALGO-GIST-2L

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-KIT	D816V (activation loop, exon 17 — rare in GIST primary; secondary resistance)	IIA	SRC-CIVIC: Level B (Supports, Poor Outcome) SRC-CIVIC: Level D ⚠ Resistance	KIT D816V in GIST is rare as primary mutation (more typical of systemic mastocytosis) but emerges as a secondary resistance mutation under imatinib pressure. Confers imatinib + sunitinib resistance. Ripretinib (INVICTUS, Blay Lancet Oncol 2020 — switch- control inhibitor with broad activation-loop coverage) and avapritinib (NAVIGATOR; FDA-approved in PDGFRA D842V and ASM) retain activity vs D816V.	ripretinib (post-imatinib/sunitinib/regorafenib failure with D816V or other activation-loop secondary resistance) avapritinib (off-label / trial for KIT D816V GIST)	SRC-NCCN-MELANOMA-2025
BIO-KIT	exon 11 deletion / insertion (juxtamembrane domain — ~50% of GIST)	IA	SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level B (Supports, Poor Outcome) SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level C (Supports, Reduced Sensitivity) SRC-CIVIC: Level D ⚠ Resistance SRC-CIVIC: Level D (Supports, Sensitivity/Response)	KIT exon 11 mutation in GIST: imatinib 400 mg/day is standard 1L (B2222, Demetri NEJM 2002 — ORR 67%; EORTC-62005 / S0033 confirmed long-term benefit). Exon 11 mutants have the longest PFS and OS on imatinib of any GIST genotype. Adjuvant imatinib 3 yr post- resection improves RFS in high-risk disease (SSG-XVIII / ACOSOG-Z9001).	imatinib 400 mg/day (1L advanced/metastatic) imatinib 400 mg/day adjuvant 3 yr (high-risk resected: ≥3 cm + mitoses ≥5/50 HPF, or rupture, or non-gastric primary) imatinib adjuvant 6 yr (extended for highest-risk per PERSIST-5 / SSG-XXII)	SRC-IRIS-OBRIEN-2003 SRC-NCCN-MELANOMA-2025
BIO-KIT	exon 13/14 (ATP-binding) or exon 17/18 (activation loop) secondary mutation post-imatinib	IIA	SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level B (Supports, Poor Outcome) SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level C (Supports, Reduced Sensitivity) SRC-CIVIC: Level D ⚠ Resistance SRC-CIVIC: Level D (Supports, Sensitivity/Response)	Secondary KIT mutations after imatinib failure cluster in exon 13/14 (ATP-binding pocket — V654A, T670I) or exon 17/18 (activation loop — D816, D820, N822, Y823). Sunitinib (Demetri Lancet 2006) covers exon 13/14 secondaries; regorafenib (GRID) provides 3L coverage; ripretinib (INVICTUS) is a switch-control inhibitor active across both classes — preferred 4L+.	sunitinib (2L; preferred for exon 13/14 ATP-binding secondaries) regorafenib (3L) ripretinib (4L+; broad activation-loop and ATP-binding coverage)	SRC-NCCN-MELANOMA-2025
BIO-KIT	exon 9 insertion (extracellular domain — ~10% GIST, predominantly small bowel)	IB	SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level B (Supports, Poor Outcome) SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level C (Supports, Reduced Sensitivity) SRC-CIVIC: Level D ⚠ Resistance SRC-CIVIC: Level D (Supports, Sensitivity/Response)	KIT exon 9 GIST has shorter PFS on imatinib 400 mg vs exon 11. Imatinib 800 mg/day (split 400 mg BID) improves PFS and OS vs 400 mg in this genotype (EORTC-62005 / MetaGIST meta-analysis, Gastrointest Stromal Tumor Meta-Analysis 2010). High dose is standard 1L for exon 9.	imatinib 800 mg/day split BID (1L advanced/metastatic exon 9)	SRC-IRIS-OBRIEN-2003 SRC-NCCN-MELANOMA-2025

Treatment options (2 tracks)

Standard plan

★ DEFAULT

Indication

IND-GIST-2L-SUNITINIB

Regimen

Sunitinib monotherapy (GIST 2L; imatinib-resistant/intolerant)

Drugs + NSZU

Sunitinib (DRUG-SUNITINIB) 50 mg PO once daily for 4 weeks on, 2 weeks off (4/2 schedule); continuous 37.5 mg alternative (per physician preference) · 4 weeks on / 2 weeks off (standard GIST dosing); repeat cycles until progression · PO ⚠ Out-of-pocket

Hard contraindications

CI-LVEF-LOW-FOR-ANTHRACYCLINE

Reason

Engine default per algorithm ALGO-GIST-2L: {'step': 2, 'outcome': False, 'branch': {'result': 'IND-GIST-2L-SUNITINIB'}, 'fired_red_flags': [], 'winner_red_flag': None}

Aggressive plan

Indication

IND-GIST-1L-AVAPRITINIB-PDGFRA-D842V

Regimen

Avapritinib monotherapy (GIST advanced/metastatic 1L; PDGFRA D842V)

Drugs + NSZU

Avapritinib (DRUG-AVAPRITINIB) 300 mg PO once daily on empty stomach (≥1 h before / ≥2 h after food) · Continuous, until progression or unacceptable toxicity · PO ✗ Not registered in UA

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-CBC	Complete Blood Count with Differential	Critical	lab	—	standard
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	standard
TEST-LFT	Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)	Critical	lab	—	standard
TEST-ECHO	Echocardiography	Standard	imaging	—	standard

What NOT to do

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

Standard plan (IND-GIST-2L-SUNITINIB)

Do NOT use for PDGFRA D842V — sunitinib is ineffective; avapritinib preferred regardless of line
Do NOT skip baseline echo + ECG — cardiotoxicity (LVEF decline, QTc prolongation)
Do NOT ignore TSH monitoring — hypothyroidism in ~36% with long-term use
Do NOT ignore BP monitoring — hypertension in ~34%; antihypertensives for G2+
Do NOT continue without dose reduction for G3+ hand-foot syndrome (PPE)

Aggressive plan (IND-GIST-1L-AVAPRITINIB-PDGFRA-D842V)

Do NOT use imatinib (any dose) for PDGFRA D842V — intrinsic resistance.
Do NOT start avapritinib without baseline brain MRI — cerebral microbleed surveillance is required (boxed warning).
Do NOT continue avapritinib through gr ≥2 cognitive AEs without dose reduction (300 → 200 mg).

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Sunitinib monotherapy (GIST 2L

42-day cycles × Continuous until progression

Aggressive plan

Induction · Avapritinib monotherapy (GIST

28-day cycles × Continuous until progression

MDT brief

Skills (recommended) — for consideration (3)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD
Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
skill: molecular_geneticistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD
Social worker / case manager recommended
Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed.
skill: social_worker_case_managerv0.1.0reviewed 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-GIST-FRAILTY-AGE, RF-GIST-HIGH-RISK-BIOLOGY, RF-GIST-INFECTION-SCREENING, RF-GIST-ORGAN-DYSFUNCTION, RF-GIST-TRANSFORMATION-PROGRESSION

Skill catalog (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-NCCN-GIST-2025: NCCN Clinical Practice Guidelines — Gastrointestinal Stromal Tumors (GIST) (2025.v1)
SRC-ONCOKB: OncoKB — Precision Oncology Knowledge Base (continuous (last verified 2026-04-25))

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
NCT04557969	Surgery in Gastrointestinal Stromal Tumors (GISTs) for Treatment, Tumor Modeling, and Genomic Analysis	N/A	RECRUITING	National Cancer Institute (NCI)	—
NCT07171203	Neoadjuvant Imatinib and Fampridine in KIT Mutant Gastrointestinal Stromal Tumor	PHASE1	RECRUITING	University of California, San Diego	—
NCT06630234	A Master Protocol to Evaluate DCC-3009 in Gastrointestinal Stromal Tumor (GIST)	PHASE1 / PHASE2	RECRUITING	Deciphera Pharmaceuticals, LLC	—
NCT05366816	ctDNA-Guided Sunitinib And Regorafenib Therapy for GIST	PHASE2	RECRUITING	University of Miami	—
NCT07559864	Comparing Regorafenib Combined With Envafolimab to Physician's Choice in Patients With Metastatic Gastrointestinal Stromal Tumors Harboring KIT Exon 17 Mutations Refractory to Standard Treatment	PHASE2	RECRUITING	Jian Li	—
NCT06805825	A Study of the c-Kit Specific Antibody-Drug Conjugate NN3201 for Advanced and/or Metastatic Solid Tumors Known to Express c-Kit	PHASE1	RECRUITING	Novelty Nobility, Inc.	—
NCT05751733	Apatinib Mesylate Versus Standard Second-line TKI in the Treatment of Advanced GIST	NA	RECRUITING	Xiangya Hospital of Central South University	—
NCT05009927	Efficiency of Imatinib Treatment After 10 Years of Treatment in Patients With Gastrointestinal Stromal Tumours (GIST) (Gist-Ten)	PHASE2	RECRUITING	Centre Leon Berard	—

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 Sunitinib monotherapy (GIST 2L; imatinib-resistant/intolerant) (REG-SUNITINIB-GIST-2L) 1/1 component drug(s) not on NSZU formulary	✓ registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Aggressive plan Avapritinib monotherapy (GIST advanced/metastatic 1L; PDGFRA D842V) (REG-AVAPRITINIB-GIST-1L) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Trial · NCT04557969 Surgery in Gastrointestinal Stromal Tumors (GISTs) for Treatment, Tumor Modeling, and Genomic Analysis No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07171203 Neoadjuvant Imatinib and Fampridine in KIT Mutant Gastrointestinal Stromal Tumor No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06630234 A Master Protocol to Evaluate DCC-3009 in Gastrointestinal Stromal Tumor (GIST) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05366816 ctDNA-Guided Sunitinib And Regorafenib Therapy for GIST No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07559864 Comparing Regorafenib Combined With Envafolimab to Physician's Choice in Patients With Metastatic Gastrointestinal Stromal Tumors Harboring KIT Exon 17 Mutations Refractory to Standard Treatment No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06805825 A Study of the c-Kit Specific Antibody-Drug Conjugate NN3201 for Advanced and/or Metastatic Solid Tumors Known to Express c-Kit No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05751733 Apatinib Mesylate Versus Standard Second-line TKI in the Treatment of Advanced GIST No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05009927 Efficiency of Imatinib Treatment After 10 Years of Treatment in Patients With Gastrointestinal Stromal Tumours (GIST) (Gist-Ten) 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-KIT_D816V_GIST-V1 | version: 1 | generated: 2026-05-04T14:13:16.626781+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.