OpenOnco · Treatment Plan

Treatment plan — DIS-GASTRIC

PLAN-BMA-MLH1_GERMLINE_GASTRIC-V1 · v1 · 2026-05-04

Patient

BMA-MLH1_GERMLINE_GASTRIC · Algorithm: ALGO-GASTRIC-METASTATIC-1L

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

✅ Covered biomarkers (matched in KB)

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
No clinically actionable variants matched in this profile.

⚠️ Not included in plan

Biomarker	Status
BIO-DMMR-IHC	Not in KB — ask clinician to verify

Treatment options (3 tracks)

Standard plan

★ DEFAULT

Indication

IND-GASTRIC-METASTATIC-1L-PDL1-CHEMO-ICI

Regimen

FOLFOX + Nivolumab

Drugs + NSZU

Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² · IV day 1 every 14d · IV ✓ NSZU covered
Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² · IV day 1 · IV ⚠ NSZU — not for this indication
5-Fluorouracil (DRUG-5-FLUOROURACIL) 400 mg/m² IV bolus + 2400 mg/m² CIV over 46h · Day 1 bolus, day 1-2 CIV · IV ✓ NSZU covered
Nivolumab (DRUG-NIVOLUMAB) 240 mg IV q2w (alternatively 480 mg IV q4w) · IV day 1 of each 14-d cycle · IV ⚠ NSZU — not for this indication

Hard contraindications

CI-PEMBROLIZUMAB-AUTOIMMUNE

Reason

Engine default per algorithm ALGO-GASTRIC-METASTATIC-1L: {'step': 3, 'outcome': False, 'branch': {'result': 'IND-GASTRIC-METASTATIC-1L-PDL1-CHEMO-ICI'}, 'fired_red_flags': [], 'winner_red_flag': None}

Aggressive plan

Indication

IND-GASTRIC-METASTATIC-1L-HER2-TOGA

Regimen

Trastuzumab + capecitabine + cisplatin (TOGA / KEYNOTE-811)

Drugs + NSZU

Trastuzumab (DRUG-TRASTUZUMAB) 8 mg/kg IV loading then 6 mg/kg q3w · IV day 1 every 21d · IV ✓ NSZU covered
Capecitabine (DRUG-CAPECITABINE) 1000 mg/m² PO BID days 1-14 · PO days 1-14 · PO ✓ NSZU covered
Cisplatin (DRUG-CISPLATIN) 80 mg/m² · IV day 1 q3w · IV ⚠ NSZU — not for this indication

Reason

Alternative track presented for HCP consideration

Aggressive plan

Indication

IND-GASTRIC-METASTATIC-1L-CLDN18-2-ZOLBETUXIMAB

Regimen

Zolbetuximab + mFOLFOX6 (SPOTLIGHT) — 1L CLDN18.2-positive HER2-negative gastric/GEJ

Drugs + NSZU

Zolbetuximab (DRUG-ZOLBETUXIMAB) Loading 800 mg/m² IV cycle 1 day 1; maintenance 600 mg/m² IV q2w · IV q2w (with mFOLFOX6 backbone) · IV ✗ Not registered in UA
Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² IV day 1 · IV day 1 q2w · IV ✓ NSZU covered
Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² IV day 1 · IV day 1 q2w · IV ⚠ NSZU — not for this indication
5-Fluorouracil (DRUG-5-FLUOROURACIL) 400 mg/m² IV bolus day 1, then 2400 mg/m² IV continuous infusion over 46 h · IV q2w · IV ✓ NSZU covered

Supportive care

SUP-ANTIEMETIC-PREMED

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	—	aggressive
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	aggressive
TEST-CT-CHEST-ABDOMEN-PELVIS	CT chest + abdomen + pelvis with IV contrast	Critical	imaging	—	all tracks
TEST-LFT	Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)	Critical	lab	—	aggressive
TEST-MSI-PCR-OR-NGS	MSI status by PCR or NGS	Critical	histology	CSD Lab: M065 CSD Lab ✓ (code TBC)	standard
TEST-HER2-IHC-ISH-IF-RAS-WT	HER2 IHC + reflex ISH (gastric scoring criteria)	Standard	histology	CSD Lab ✓ (code TBC)	all tracks
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

CLDN18.2 expression positive (≥75% of tumor cells with 2+/3+ membranous staining on VENTANA CLDN18 (43-14A) RxDx) in HER2-negative metastatic / unresectable gastric or GEJ adenocarcinoma — eligibility for zolbetuximab + fluoropyrimidine/oxaliplatin 1L (SPOTLIGHT mFOLFOX6 mOS 18.2 vs 15.5 mo HR 0.75; GLOW CAPOX mOS 14.4 vs 12.2 mo HR 0.77). Treatment-defining for the ~38% of HER2-negative gastric cohort. Hierarchy: HER2+ trastuzumab supersedes; MSI-H pembrolizumab supersedes; otherwise CLDN18.2+ → zolbetuximab. RF-GASTRIC-CLDN18-2-ACTIONABLE
Surgical/endoscopic emergency in gastric/GEJ adenocarcinoma: massive upper-GI bleed requiring transfusion, gastric outlet obstruction with intolerance of oral intake, or perforation. Mandates urgent endoscopic / surgical / interventional management BEFORE systemic therapy initiation. RF-GASTRIC-EMERGENCY-BLEED-OBSTRUCTION
Treatment-defining biomarkers in metastatic gastric/GEJ adenocarcinoma: HER2+ (IHC 3+ OR 2+/ISH+) → trastuzumab+chemo TOGA / T-DXd 2L+; CLDN18.2+ (≥75% of tumor cells with 2+ membranous staining) → zolbetuximab+chemo SPOTLIGHT/GLOW; MSI-H → pembrolizumab mono; EBV+ subtype (TCGA molecular class) — distinct biology, ICI-favorable. RF-GASTRIC-HIGH-RISK-BIOLOGY

CONTRA-AGGRESSIVE

Hard contraindications to escalation

What NOT to do

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

Standard plan (IND-GASTRIC-METASTATIC-1L-PDL1-CHEMO-ICI)

Do NOT use without HER2 testing — HER2+ patients get trastuzumab+chemo instead
Do NOT continue through Grade 3+ irAE without permanent ICI discontinuation consideration
Do NOT initiate during ongoing GI bleed / obstruction

Aggressive plan (IND-GASTRIC-METASTATIC-1L-HER2-TOGA)

Do NOT use without baseline LVEF — trastuzumab cardiotoxic (q3-mo echo monitoring)
Do NOT combine with anthracycline (cumulative cardiotoxicity)
Do NOT initiate during ongoing GI bleed / obstruction

Aggressive plan (IND-GASTRIC-METASTATIC-1L-CLDN18-2-ZOLBETUXIMAB)

Do not start zolbetuximab without confirmed CLDN18.2 ≥75% 2+/3+ by VENTANA RxDx — outside this range benefit is not proven.
Do not prescribe zolbetuximab in HER2+ patients — TOGA trastuzumab+chemo takes priority.
Do not prescribe zolbetuximab in MSI-H patients 1L — pembrolizumab (KEYNOTE-859) takes preference.
Do not start without triplet antiemetic prophylaxis (5-HT3 + NK1-RA + dex) for cycle 1 — nausea/vomiting severe without it.
Do not combine with ipilimumab/ICI outside of trials — combination safety unknown.
Do not confirm the plan without funding pathway — zolbetuximab not registered in UA.

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · FOLFOX + Nivolumab

14-day cycles × Until progression / unacceptable toxicity (chemo backbone capped at ~12 cycles in some protocols; nivo continues mono until 2 years)

Aggressive plan

Induction · Trastuzumab + capecitabine + c

21-day cycles × Until progression / unacceptable toxicity (chemo backbone often capped at 6-8 cycles, trastuzumab continues mono)

Aggressive plan

Induction · Zolbetuximab + mFOLFOX6 (SPOTL

14-day cycles × Until progression / unacceptable toxicity (oxaliplatin commonly capped at 8-12 cycles for cumulative neuropathy; zolbetuximab + 5-FU/LV maintenance continues)

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-BREAST-CDH1-LOBULAR-CANDIDATE, RF-GASTRIC-CLDN18-2-ACTIONABLE, RF-GASTRIC-EMERGENCY-BLEED-OBSTRUCTION, RF-GASTRIC-FRAILTY-AGE, RF-GASTRIC-HIGH-RISK-BIOLOGY, RF-GASTRIC-INFECTION-SCREENING, RF-GASTRIC-PDL1-CPS-1-PLUS, RF-GASTRIC-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-ESMO-GASTRIC-2024: ESMO Gastric Cancer (2024)
SRC-NCCN-GASTRIC-2025: NCCN Gastric Cancer (v.3.2025)

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
NCT05739045	Nivolumab Combined With SOX Used in the Perioperative Treatment	PHASE2	RECRUITING	Xiangdong Cheng	—
NCT06921928	Study for AZD4360 in Participants With Advanced Solid Tumours	PHASE1 / PHASE2	RECRUITING	AstraZeneca	—
NCT06364410	Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors	PHASE1	RECRUITING	National Cancer Institute (NCI)	—
NCT05894824	T-Dxd in Combination With Ramucirumab as HER2 Low Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma	PHASE1 / PHASE2	RECRUITING	Yonsei University	—
NCT04900818	Study of TJ033721 (Givastomig) in Subjects With Advanced or Metastatic Solid Tumors	PHASE1	RECRUITING	I-Mab Biopharma US Limited	—
NCT06341335	A Study of AK104/Placebo Plus AK109/Placebo And Paclitaxel in Gastric or Gastroesophageal Junction Adenocarcinoma	PHASE3	RECRUITING	Akeso	—
NCT07069712	A Study of Novel Agents or Combinations as Perioperative Treatment in Participants With Locally Advanced Resectable Gastroesophageal Adenocarcinoma	PHASE2	RECRUITING	AstraZeneca	—
NCT06949033	Neoadjuvant Cadonilimab Combined With Perioperative Oxaliplatin Plus S1 for Diffuse or Mixed Type of Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma	PHASE3	RECRUITING	Zuoyi Jiao	—
NCT07431281	Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in Participants With Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma Expressing Claudin18.2	PHASE3	RECRUITING	AstraZeneca	—
NCT05086692	A Beta-only IL-2 ImmunoTherapY Study	PHASE1 / PHASE2	RECRUITING	Medicenna Therapeutics, Inc.	—

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 FOLFOX + Nivolumab (REG-FOLFOX-NIVO)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan Trastuzumab + capecitabine + cisplatin (TOGA / KEYNOTE-811) (REG-TRASTUZUMAB-CHEMO-TOGA)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan Zolbetuximab + mFOLFOX6 (SPOTLIGHT) — 1L CLDN18.2-positive HER2-negative gastric/GEJ (REG-ZOLBETUXIMAB-CHEMO) 1/4 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Trial · NCT05739045 Nivolumab Combined With SOX Used in the Perioperative Treatment No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06921928 Study for AZD4360 in Participants With Advanced Solid Tumours No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06364410 Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05894824 T-Dxd in Combination With Ramucirumab as HER2 Low Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04900818 Study of TJ033721 (Givastomig) in Subjects With Advanced or Metastatic Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06341335 A Study of AK104/Placebo Plus AK109/Placebo And Paclitaxel in Gastric or Gastroesophageal Junction Adenocarcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07069712 A Study of Novel Agents or Combinations as Perioperative Treatment in Participants With Locally Advanced Resectable Gastroesophageal Adenocarcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06949033 Neoadjuvant Cadonilimab Combined With Perioperative Oxaliplatin Plus S1 for Diffuse or Mixed Type of Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07431281 Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in Participants With Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma Expressing Claudin18.2 No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05086692 A Beta-only IL-2 ImmunoTherapY Study 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-MLH1_GERMLINE_GASTRIC-V1 | version: 1 | generated: 2026-05-04T14:13:16.642595+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.