A Study to Compare Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) Versus Pembrolizumab Alone as Treatment in Participants With Mismatch Repair Proficient Endometrial Cancer (MK-2870-033/TroFuse-033/GOG-3119/ENGOT-en29)

Official title

A Phase 3 Randomized, Open-label, Multicenter Study to Compare the Efficacy and Safety of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in Combination With Pembrolizumab Versus Pembrolizumab Alone as First-line Maintenance Treatment in Participants With Mismatch Repair Proficient Endometrial Cancer (TroFuse-033/GOG-3119/ENGOT-en29)

Overview

Researchers are looking for new ways to treat people with proficient mismatch repair (pMMR) endometrial cancer (EC) that is advanced or recurrent. * EC is a type of cancer that starts in the tissues inside the uterus (womb) * pMMR indicates that certain normal proteins are present in the cancer cells * Advanced means the cancer has spread locally or to other parts of the body (metastatic) and cannot be removed with surgery * Recurrent means the cancer came back after surgery Sacituzumab tirumotecan (also known as sac-TMT) and pembrolizumab are the study medicines. Sac-TMT is an antibody drug conjugate (ADC). An ADC attaches to specific targets on cancer cells and delivers treatment to destroy those cells. The goal of this study is to learn if people who receive sac-TMT with pembrolizumab live longer and without the cancer getting worse compared to people who receive pembrolizumab alone.

Detailed description

All participants undergo an initial Induction Phase of six cycles, each cycle consisting of pembrolizumab + carboplatin or cisplatin + paclitaxel or docetaxel. Each cycle is three weeks. Participants whose cancer does not progress enter the Maintenance Treatment Phase and are then randomly assigned to pembrolizumab + sac-TMT or pembrolizumab monotherapy. Participants whose cancer does progress will have the possibility to enter the Subsequent Treatment Phase and are then randomly assigned to pembrolizumab + sac-TMT or sac-TMT monotherapy.

Interventions

• Biological Pembrolizumab
  Intravenous (IV) Infusion
• Drug Carboplatin
  During the Induction Phase, participants receive carboplatin AUC 5 (mg/mL/min) on Day 1 of each 3-week cycle for 6 cycles (up to approximately 4 months) via IV infusion.
• Drug Paclitaxel
  During the Induction Phase, participants receive paclitaxel 175 mg/m\^2 on Day 1 of each 3-week cycle for 6 cycles (up to approximately 4 months) via IV infusion.
• Drug Docetaxel
  During the Induction Phase, participants may receive docetaxel (in place of paclitaxel) 75 mg/m\^2 on Day 1 of each 3-week cycle for 6 cycles (up to approximately 4 months) via IV infusion.
• Biological Sacituzumab Tirumotecan
  IV Infusion
• Drug Cisplatin
  During the Induction Phase, participants may receive cisplatin (in place of carboplatin) 75 mg/m\^2 on Day 1 of each 3-week cycle for 6 cycles (up to approximately 4 months) via IV infusion

Primary outcome measures

• Maintenance Treatment: Progression-Free Survival (PFS) [Time frame: Up to approximately 44 months]
• Maintenance Treatment: Overall Survival (OS) [Time frame: Up to approximately 54 months]

Secondary outcome measures (7)

• Maintenance Treatment: Progression-Free Survival 2 (PFS2) as Assessed by Investigator [Time frame: Up to approximately 54 months]
• Maintenance Treatment: Number of Participants Who Experience One or More Adverse Events (AEs) [Time frame: Up to approximately 27 months]
• Maintenance Treatment: Number of Participants Who Discontinue Study Intervention Due to an AE [Time frame: Up to approximately 24 months]
• Maintenance Treatment: Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Mean Score [Time frame: Baseline and up to approximately 24 months]
• Maintenance Treatment: Change from baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score [Time frame: Baseline and up to approximately 24 months]
• Maintenance Treatment: Change from baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score [Time frame: Baseline and up to approximately 24 months]
• Maintenance Treatment: Change from baseline in EORTC QLQ-EN24 Symptom Score [Time frame: Baseline and up to approximately 24 months]

Eligibility criteria

Key inclusion criteria include but are not limited to:

• Has a histologically confirmed diagnosis of primary advanced or recurrent endometrial carcinoma that has been confirmed as proficient mismatch repair (pMMR)
• Has radiographically evaluable disease, with measurable Stage III or either measurable or non-measurable Stage IV or recurrent disease per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1), as assessed by the investigator
• Has received no prior systemic therapy for endometrial carcinoma except the following conditions as pre-specified by the protocol: 1 prior line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy in the setting of curative-intent, prior radiation with or without radiosensitizing chemotherapy if >2 weeks before the start of induction treatment, or prior hormonal therapy for treatment of endometrial carcinoma that was discontinued ≥1 week before the start of induction treatment

Key exclusion criteria include but are not limited to:

• Has carcinosarcoma, neuroendocrine tumors or endometrial sarcoma, including stromal sarcoma, leiomyosarcoma, adenosarcoma, or other types of sarcomas
• Has endometrial carcinoma of any histology that is mismatch repair deficient (dMMR)
• Is a candidate for debulking surgery resulting in complete removal of all tumor and no evidence of radiological disease following surgery, or curative-intent radiotherapy at the time of enrollment
• Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
• Human Immunodeficiency Virus-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Received prior therapy in any setting with any of the following: anti-programmed cell death 1 protein, anti-programmed cell death ligand 1, anti-programmed cell death ligand 2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor; trophoblast cell surface antigen 2-targeted antibody drug conjugate; or topoisomerase I inhibitor-containing antibody drug conjugate

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 47 centers

• University of South Alabama, Mitchell Cancer Institute ( Site 6033) — Mobile
• Alaska Women's Cancer Care ( Site 6036) — Anchorage
• CHAO Family Comprehensive Cancer Center and Ambulatory Care ( Site 5014) — Irvine
• University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 6020) — Orange
• John Muir Health Cancer Center ( Site 6028) — Walnut Creek
• Yale University School of Medicine ( Site 6009) — New Haven
• MedStar Washington Hospital Center ( Site 5005) — Washington D.C.
• Florida Cancer Specialists - South ( Site 7003) — Fort Myers
• … and 39 more centers

China · 33 centers

Center list to be confirmed — check the primary protocol.

Japan · 18 centers

Center list to be confirmed — check the primary protocol.

Canada · 13 centers

• BC Cancer Surrey ( Site 0621) — Surrey
• CancerCare Manitoba ( Site 0617) — Winnipeg
• NL Health Services ( Site 0602) — St. John's
• Royal Victoria Regional Health Centre ( Site 0615) — Barrie
• London Health Sciences Centre ( Site 0611) — London
• Sault Area Hospital ( Site 0616) — Sault Ste. Marie
• Sunnybrook Research Institute ( Site 0610) — Toronto
• Princess Margaret Cancer Center ( Site 0609) — Toronto
• … and 5 more centers

Italy · 13 centers

Center list to be confirmed — check the primary protocol.

France · 10 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 10 centers

Center list to be confirmed — check the primary protocol.

Poland · 8 centers

Center list to be confirmed — check the primary protocol.

Spain · 8 centers

Center list to be confirmed — check the primary protocol.

Germany · 7 centers

Center list to be confirmed — check the primary protocol.

South Korea · 6 centers

Center list to be confirmed — check the primary protocol.

Argentina · 5 centers

• Instituto Alexander Fleming ( Site 0105) — Ciudad Autónoma de Buenos Aires
• Instituto de Investigaciones Clínicas Mar del Plata ( Site 0108) — Mar del Plata
• Fundación Respirar ( Site 0101) — Buenos Aires
• Hospital Británico de Buenos Aires ( Site 0103) — CABA
• Instituto San Marcos ( Site 0106) — San Juan

Belgium · 5 centers

• CHU Saint-Pierre ( Site 0405) — Brussels
• AZ Maria Middelares ( Site 0402) — Ghent
• UZ Leuven ( Site 0401) — Leuven
• Grand Hôpital de Charleroi ( Site 0403) — Charleroi
• CHU de Liege ( Site 0404) — Liège

Brazil · 5 centers

• Hospital Araújo Jorge ( Site 0521) — Goiânia
• Liga Norte Riograndense Contra o Câncer ( Site 0523) — Natal
• Hospital São Lucas da PUCRS ( Site 0522) — Porto Alegre
• IBCC - Instituto Brasileiro de Controle do Câncer ( Site 0525) — São Paulo
• Instituto Nacional de Câncer - INCA ( Site 0515) — Rio de Janeiro

Chile · 5 centers

Center list to be confirmed — check the primary protocol.

Greece · 5 centers

Center list to be confirmed — check the primary protocol.

Israel · 5 centers

Center list to be confirmed — check the primary protocol.

Mexico · 5 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 5 centers

Center list to be confirmed — check the primary protocol.

Australia · 4 centers

• Blacktown Hospital ( Site 0201) — Blacktown
• Royal Brisbane and Women's Hospital ( Site 0206) — Brisbane
• Epworth Freemasons ( Site 0207) — Melbourne
• Sir Charles Gairdner Hospital ( Site 0203) — Nedlands

Colombia · 4 centers

Center list to be confirmed — check the primary protocol.

Czechia · 4 centers

Center list to be confirmed — check the primary protocol.

Denmark · 4 centers

Center list to be confirmed — check the primary protocol.

Finland · 4 centers

Center list to be confirmed — check the primary protocol.

Ireland · 4 centers

Center list to be confirmed — check the primary protocol.

Thailand · 4 centers

Center list to be confirmed — check the primary protocol.

Austria · 3 centers

• Medizinische Universität Graz-Abteilung für Gynäkologie / Onkologie ( Site 0303) — Graz
• Medizinische Universitaet Innsbruck-Univ.-Klinik f. Gynäkologie und Geburtshilfe ( Site 03 — Innsbruck
• Medizinische Universität Wien - Allg. Gynaekologie & Gyn. Onkologie ( Site 0302) — Vienna

Hungary · 3 centers

Center list to be confirmed — check the primary protocol.

Norway · 3 centers

Center list to be confirmed — check the primary protocol.

Peru · 3 centers

Center list to be confirmed — check the primary protocol.

Netherlands · 2 centers

Center list to be confirmed — check the primary protocol.

Singapore · 2 centers

Center list to be confirmed — check the primary protocol.

Sweden · 2 centers

Center list to be confirmed — check the primary protocol.

Puerto Rico · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06952504 · 2870-033 · 2024-519331-42-00 · U1111-1315-0794 · GOG-3119 · ENGOT-en29 · TroFuse-033 · jRCT2011250020

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗