OpenOnco · Treatment Plan

Treatment plan — Gastrointestinal stromal tumor

PLAN-BMA-KIT_D816V_GIST-V1 · v1 · 2026-08-18

Patient

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

DiagnosisGastrointestinal stromal tumor

MOH / ICD-10C49

ICD-O-38936/3; C15, C16, C17, C18, C19, C20, C26

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
ESCAT: clinical review pendingBIO-KIT	D816V (activation loop, exon 17 — rare in GIST primary; secondary resistance)	IIA	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal 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
ESCAT: clinical review pendingBIO-KIT	exon 11 deletion / insertion (juxtamembrane domain — ~50% of GIST)	IA	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Reduced Sensitivity) 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
ESCAT: clinical review pendingBIO-KIT	exon 13/14 (ATP-binding) or exon 17/18 (activation loop) secondary mutation post-imatinib	IIA	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Reduced Sensitivity) 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
ESCAT: clinical review pendingBIO-KIT	exon 9 insertion (extracellular domain — ~10% GIST, predominantly small bowel)	IB	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Reduced Sensitivity) 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

Primary current-line option

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

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

Sequencing / non-current-line candidates

Shown for audit and future-line context; not part of the current treatment choice.

Indication	Authored line	Regimen	Why separated
`IND-GIST-1L-AVAPRITINIB-PDGFRA-D842V`	line 1	Avapritinib monotherapy (GIST advanced/metastatic 1L; PDGFRA D842V)	Prior-line candidate only: indication line 1, patient line 2; not a current treatment option

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
TEST-ECHO	Echocardiography	Standard	imaging	—	all tracks

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)

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

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

42-day cycles × Continuous until progression

MDT brief

MDT talk tree (1 steps)

#	Owner	Topic	Action
1	social_worker_case_manager	Specialist review	Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed.

Skills (recommended) — for consideration (1)

Social worker / case manager recommended
Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed.

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: 0/0 known (100%), 0 missing, 0 default-track gaps
Unevaluated RedFlags: RF-GIST-FRAILTY-AGE, RF-GIST-HIGH-RISK-BIOLOGY, RF-GIST-INFECTION-SCREENING, RF-GIST-ORGAN-DYSFUNCTION, RF-GIST-PDGFRA-D842V, RF-GIST-TRANSFORMATION-PROGRESSION

Technical MDT skill metadata (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-NCCN-GIST-2025: NCCN Clinical Practice Guidelines — Gastrointestinal Stromal Tumors (GIST) (2025.v1)

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: 2026-08-18.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT05009927	Efficiency of Imatinib Treatment After 10 Years of Treatment in Patients With Gastrointestinal Stromal Tumours (GIST) (Gist-Ten)	PHASE2	RECRUITING	Centre Leon Berard	—	Biomarker: enriched Surrogate endpoint only Single country
NCT06630234	A Master Protocol to Evaluate DCC-3009 in Gastrointestinal Stromal Tumor (GIST)	PHASE1 / PHASE2	RECRUITING	Deciphera Pharmaceuticals, LLC	—	Biomarker: enriched Surrogate endpoint only Single country
NCT04557969	Surgery in Gastrointestinal Stromal Tumors (GISTs) for Treatment, Tumor Modeling, and Genomic Analysis	N/A	RECRUITING	National Cancer Institute (NCI)	—	Surrogate endpoint only Single country
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.	—	Phase 1 only Single country
NCT05751733	Apatinib Mesylate Versus Standard Second-line TKI in the Treatment of Advanced GIST	NA	RECRUITING	Xiangya Hospital of Central South University	—	Biomarker: enriched Surrogate endpoint only Single country
NCT05208047	(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors	PHASE3	RECRUITING	Cogent Biosciences, Inc.	—	Biomarker: enriched Surrogate endpoint only
NCT05366816	ctDNA-Guided Sunitinib And Regorafenib Therapy for GIST	PHASE2	RECRUITING	University of Miami	—	Small N (<50) Surrogate endpoint only Single country
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	—	Surrogate endpoint only Single country
NCT07171203	Preoperative Imatinib and Fampridine in KIT Mutant Gastrointestinal Stromal Tumor	PHASE1	RECRUITING	University of California, San Diego	—	Biomarker: enriched Phase 1 only Small N (<50) 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
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
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
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 · 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 · 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 · NCT05208047 (Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors 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 · NCT07171203 Preoperative Imatinib and Fampridine in KIT Mutant Gastrointestinal Stromal Tumor 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: 2026-08-18.

plan_id: PLAN-BMA-KIT_D816V_GIST-V1 | version: 1 | generated: 2026-08-18T07:59:49.263178+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.