OpenOnco · Endometrial - dMMR/MSH2 - immunotherapy evidence
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OpenOnco · Treatment Plan
Treatment plan — Endometrial carcinoma
PLAN-SHOWCASE-ENDOMETRIAL-DMMR-001-V1 · v1 · 2026-10-18
Patient
SHOWCASE-ENDOMETRIAL-DMMR-001 · Algorithm: ALGO-ENDOMETRIAL-ADVANCED-1L
DiagnosisEndometrial carcinoma
MOH / ICD-10C54
ICD-O-38380/3; C54.1
StageIVB
Histologyendometrioid adenocarcinoma

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks
✅ Covered biomarkers (matched in KB)
BiomarkerVariantESCATEvidenceClinical significanceDrugsSources
ESCAT: clinical review pendingBIO-DMMR-IHCMSH2 germline loss-of-function (dMMR / MSI-H)IA
Trial or research option
MSH2 germline loss-of-function in endometrial produces dMMR/MSI-H phenotype. Pan-tumor MSI-H ICI eligibility (pembrolizumab per KEYNOTE-158, dostarlimab per GARNET) supersedes tumor-specific lines via tissue-agnostic FDA approval. Advanced/recurrent dMMR endometrial: dostarlimab + carbo/paclitaxel 1L (RUBY) and pembrolizumab + carbo/paclitaxel (NRG-GY018) doubled PFS. Dostarlimab/pembrolizumab monotherapy in 2L+. Adjuvant ICI in early-stage dMMR under study.dostarlimab + carbo/paclitaxel (1L advanced dMMR, RUBY)
pembrolizumab + carbo/paclitaxel (1L advanced, NRG-GY018)
dostarlimab monotherapy (2L+ dMMR, GARNET)
pembrolizumab monotherapy (pan-tumor MSI-H)
  • SRC-NCCN-UTERINE-2025
  • SRC-ESGO-ENDOMETRIAL-2025
ESCAT: clinical review pendingBIO-MSI-STATUSMSI-HIA
  • SRC-NCCN-UTERINE-2025
  • SRC-ESMO-ENDOMETRIAL-2022
Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap.
MSI-H/dMMR endometrial cancer (~25-30% of advanced cases) qualifies for ICI-based regimens. Dostarlimab + carboplatin + paclitaxel 1L (RUBY trial; mOS NR vs 36.7 mo, HR 0.64 in dMMR/MSI-H subgroup; FDA-approved 2023). Pembrolizumab + carboplatin + paclitaxel 1L (KEYNOTE-868/NRG-GY018; FDA-approved 2023 for dMMR/MSI-H). Also pembrolizumab monotherapy 2L+ for MSI-H/dMMR endometrial (KEYNOTE-158; FDA-approved 2017 tumor-agnostically). MSI/MMR testing mandatory at diagnosis of advanced/recurrent endometrial cancer per NCCN/ESMO. Indication selection enforced by algorithm layer (IND-ENDOMETRIAL-DMMR); this BMA surfaces ESCAT context only.dostarlimab + carboplatin + paclitaxel (dMMR/MSI-H 1L per SRC-NCCN-UTERINE-2025)
pembrolizumab + carboplatin + paclitaxel (dMMR/MSI-H 1L per SRC-NCCN-UTERINE-2025)
pembrolizumab monotherapy (MSI-H 2L+ per SRC-ESMO-ENDOMETRIAL-2022)
  • SRC-NCCN-UTERINE-2025
  • SRC-ESMO-ENDOMETRIAL-2022
⚠️ Not included in plan
BiomarkerStatus
MSH2Not in KB — ask clinician to verify
POLEExcluded (negative)
TP53Not in KB — ask clinician to verify

Primary current-line option

Standard plan
★ DEFAULT
Indication
IND-ENDOMETRIAL-ADVANCED-1L-PEMBRO-CHEMO
Regimen
Pembrolizumab + carbo + paclitaxel (endometrial advanced 1L)
Drugs + NSZU
  • Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w · Continuous up to 2 years · IV ⚠ NSZU — not for this indication
  • Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication
  • Paclitaxel (DRUG-PACLITAXEL) 175 mg/m² IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication
Reason
Primary current-line option selected by ALGO-ENDOMETRIAL-ADVANCED-1L at step 1.

Other current-line alternatives (1 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
Aggressive plan
Indication
IND-ENDOMETRIAL-ADVANCED-1L-DOSTARLIMAB-CHEMO
Regimen
Dostarlimab + carbo + paclitaxel (endometrial advanced 1L dMMR)
Drugs + NSZU
  • Dostarlimab (DRUG-DOSTARLIMAB) 500 mg IV q3w → 1000 mg q6w maintenance · With chemo cycles 1-6 + maintenance up to 3 years · IV ✗ Not registered in UA
  • Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication
  • Paclitaxel (DRUG-PACLITAXEL) 175 mg/m² IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication
Reason
Current-line alternative presented for HCP consideration

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks
IDNamePriorityCategoryWhere to orderNeeded for
TEST-CECT-CAPCECT chest/abdomen/pelvisCriticalimaging—all tracks
TEST-ER-PR-IHCER + PR immunohistochemistry on tumorCritical—CSD Lab ✓ (code TBC)all tracks

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track
  • Patient with active or incompletely controlled pre-existing autoimmune or inflammatory disease (sarcoidosis, rheumatoid arthritis, IBD, SLE, autoimmune hepatitis, inflammatory myopathy, myasthenia gravis, or similar) is considered for immune checkpoint inhibitor (ICI) therapy — elevated risk of immune-related adverse events (irAE) flare or de-novo grade 3-4 irAE. Requires specialist (rheumatology / pulmonology / gastroenterology) pre-treatment review; prefer lower-irAE-burden backbone when options exist (pembrolizumab mono > ipilimumab+nivolumab).
    Pre-existing autoimmune disease is present in ~10-15% of patients eligible for ICI therapy; historically excluded from pivotal trials. Real-world data (Abdel-Wahab 2018, 3557 pts) shows 55% experienced irAE flare and ~29% required…
    RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISKSRC-SITC-ICI-IRAEMANAGEMENT-2021SRC-ESMO-ICI-TOXICITY-2022

CONTRA-AGGRESSIVE

Hard contraindications to escalation
  • —

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Pembrolizumab + carbo + paclitaxel (endometrial advanced 1L)
21-day cycles × Chemo x 6; pembro maintenance up to 2 years

Aggressive plan

Induction · Dostarlimab + carbo + paclitaxel (endometrial advanced 1L dMMR)
21-day cycles × Chemo x 6; dostarlimab maintenance up to 3 years

MDT brief

Discussion questions (1, 0 blocking)

MDT talk tree (2 steps)

#OwnerTopicAction
1hematologistStaging / disease burden What is the current LDH? Marker of tumor burden and transformation.
2clinical_pharmacistSpecialist review Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Skills (recommended) — for consideration (1)

  • Clinical pharmacist recommended
    Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

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: 1/1 known (100%), 0 missing, 0 default-track gaps
  • Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-CASCADE-LYNCH-FDR-POSITIVE, RF-CHRONIC-SEVERE-OBESITY-BMI40-PREVENTION, RF-CHRONIC-T2DM-CANCER-RISK-PREVENTION, RF-COWDEN-CONFIRMED-CARRIER, RF-COWDEN-FAMILY-HISTORY-SUSPICION, RF-ENDOMETRIAL-FIT-FOR-LENVATINIB-COMBO, RF-ENDOMETRIAL-FRAILTY-AGE, RF-ENDOMETRIAL-HIGH-RISK-BIOLOGY, RF-ENDOMETRIAL-INFECTION-SCREENING, RF-ENDOMETRIAL-ORGAN-DYSFUNCTION, RF-ENDOMETRIAL-TRANSFORMATION-PROGRESSION, RF-IATROGENIC-COMBINED-HRT-PREVENTION, RF-IATROGENIC-TAMOXIFEN-ENDOMETRIAL-PREVENTION, RF-LIFESTYLE-OBESITY-CANCER-PREVENTION, RF-LIFESTYLE-SEDENTARY-PREVENTION, RF-LIFESTYLE-SUGARY-BEVERAGES-PREVENTION, RF-LYNCH-CONFIRMED-CARRIER, RF-LYNCH-FAMILY-HISTORY-SUSPICION, RF-POLE-POLD1-ENDOMETRIAL-LOW-RISK, RF-REPRODUCTIVE-BREAST-ENDOMETRIAL-PREVENTION, RF-REPRODUCTIVE-OCP-LONG-TERM, RF-REPRODUCTIVE-PCOS-ENDOMETRIAL-PREVENTION
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).
Specialistskill_idVersionLast reviewedSign-offsDomain
Cellular therapy specialist (CAR-T)cellular_therapy_specialistv0.1.02026-04-250cellular_therapy
Clinical pharmacistclinical_pharmacistv0.1.02026-04-250clinical_pharmacy
Hematologist / oncohematologisthematologistv0.1.02026-04-250hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)hematopathologistv0.1.02026-04-250hematopathology
Infectious disease / hepatologyinfectious_disease_hepatologyv0.1.02026-04-250infectious_diseases
Medical oncologist (solid-tumor chemotherapist)medical_oncologistv0.1.02026-04-250solid_oncology
Molecular geneticist / molecular oncologistmolecular_geneticistv0.1.02026-04-250molecular_oncology
Palliative carepalliative_carev0.1.02026-04-250palliative_care
Pathologist (general)pathologistv0.1.02026-04-250pathology
Primary care / family physicianprimary_carev0.1.02026-04-250primary_care
Psycho-oncologistpsychologistv0.1.02026-04-250psychosocial
Radiation oncologistradiation_oncologistv0.1.02026-04-250radiation_oncology
Radiologistradiologistv0.1.02026-04-250diagnostic_imaging
Social worker / case managersocial_worker_case_managerv0.1.02026-04-250psychosocial
Surgical oncologistsurgical_oncologistv0.1.02026-04-250surgical_oncology
Transplant specialist (BMT)transplant_specialistv0.1.02026-04-250cellular_therapy

Sources cited

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: 2026-10-18 · ClinicalTrials.gov.
NCTTitlePhaseStatusSponsorUASignalsEligibility (excerpt)
NCT06206083Molecular Classification in Mexican Patients With Endometrial Cancer and Its Impact on PrognosisN/ARECRUITINGNational Institute of Cancerología—Single country
NCT06906341Relacorilant in Combination With Different Treatment Regimens in Patients With Gynecological CancersPHASE2RECRUITINGCorcept Therapeutics—Surrogate endpoint only
NCT05797831Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial CancerPHASE2 / PHASE3RECRUITINGKartos Therapeutics, Inc.—Surrogate endpoint only
NCT07233811Day Care in Robotic Surgery Hysterectomy. Investigate Quality of Life and Safety With Same Day Discharge After Robotic Hysterectomy for Patients With Benign and Malignant Disease. A Multicenter Randomized Study With 3 Hospitals in Stockholm Sweden.NARECRUITINGKarolinska Institutet—Single country
NCT05039801IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid TumorsPHASE1RECRUITINGM.D. Anderson Cancer Center—Phase 1 only Single country
NCT07198074Testing the Addition of an Antiangiogenic Drug (Bevacizumab) to Chemotherapy (Carboplatin and Paclitaxel) Combined With Immunotherapy (Pembrolizumab) for pMMR, TP53 Mutated Endometrial CancerPHASE3RECRUITINGNational Cancer Institute (NCI)—Surrogate endpoint only Single country
NCT07020221A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid TumorsPHASE1 / PHASE2RECRUITINGVerastem, Inc.——
NCT07808164ENPP1/cGAS (EG) and FAP Expression Profiles in Solid Tumors: An Immunohistochemical Study in a Vietnamese CohortN/ARECRUITINGTam Anh Research Institute—Single country
NCT05579366Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001)PHASE1 / PHASE2RECRUITINGGenmab—Surrogate endpoint only
NCT05559879Cabozantinib and Dostarlimab in Recurrent Gynecologic CarcinosarcomaPHASE1 / PHASE2RECRUITINGUniversity of Alabama at Birmingham—Small N (<50) Surrogate endpoint only 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).
OptionUA registrationNSZUCost orientationAccess pathway
Standard plan
Pembrolizumab + carbo + paclitaxel (endometrial advanced 1L) (REG-PEMBRO-CARBO-PACLI-ENDOM)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Aggressive plan
Dostarlimab + carbo + paclitaxel (endometrial advanced 1L dMMR) (REG-DOSTARLIMAB-CARBO-PACLI-ENDOM)
1/3 component drug(s) not registered in Ukraine +1
✗ not registered✗ out-of-pocket₴-? — verify pathwaynot recorded
Trial · NCT06206083
Molecular Classification in Mexican Patients With Endometrial Cancer and Its Impact on Prognosis
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT06906341
Relacorilant in Combination With Different Treatment Regimens in Patients With Gynecological Cancers
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05797831
Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT07233811
Day Care in Robotic Surgery Hysterectomy. Investigate Quality of Life and Safety With Same Day Discharge After Robotic Hysterectomy for Patients With Benign and Malignant Disease. A Multicenter Randomized Study With 3 Hospitals in Stockholm Sweden.
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05039801
IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT07198074
Testing the Addition of an Antiangiogenic Drug (Bevacizumab) to Chemotherapy (Carboplatin and Paclitaxel) Combined With Immunotherapy (Pembrolizumab) for pMMR, TP53 Mutated Endometrial Cancer
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT07020221
A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT07808164
ENPP1/cGAS (EG) and FAP Expression Profiles in Solid Tumors: An Immunohistochemical Study in a Vietnamese Cohort
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05579366
Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001)
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05559879
Cabozantinib and Dostarlimab in Recurrent Gynecologic Carcinosarcoma
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. Table assembled: 2026-10-18. Table assembly does not verify registration, NSZU coverage or prices. Check the currency of these data separately.