A Clinical Study of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) as First-line Maintenance Treatment of Cervical Cancer (MK-2870-036/TroFuse-036/GOG-3123/ENGOT-cx22)

Official title

A Phase 3, Randomized, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab With or Without Bevacizumab Compared With Standard of Care as Firstline Maintenance Treatment for Participants With Persistent, Recurrent, or Newly Diagnosed Metastatic Cervical Cancer With PD-L1 CPS Greater Than or Equal to 1 (TroFuse-036/GOG-3123/ENGOT-cx22)

Overview

Researchers are looking for new ways to treat metastatic cervical cancer. Cervical cancer is cancer in the cervix, the lower part of the uterus (womb). Metastatic means the cancer has spread to other parts of the body. Researchers want to learn about giving the study medicine sacituzumab tirumotecan (also called sac-TMT or MK-2870) along with pembrolizumab and bevacizumab treatments. Sac-TMT is an antibody drug conjugate, which is a type of medicine that attaches to specific targets on cancer cells and delivers treatment to destroy those cells. The goals of this study are to learn: * About the safety of sac-TMT with pembrolizumab and bevacizumab, and if people tolerate them when given together, and * If people who receive sac-TMT and pembrolizumab, with or without bevacizumab, live longer overall or without their cancer getting worse as compared to those who receive standard treatment

Detailed description

This is a 2-part study.

In Part 1 Safety Run-in, eligible participants will be allocated to treatment with sac-TMT + pembrolizumab + bevacizumab.

In Part 2, all participants receive standard of care induction treatment. Eligible participants whose cancer does not progress then begin maintenance treatment and are randomized to receive pembrolizumab or sac-TMT + pembrolizumab. All participants in Part 2 maintenance treatment may also receive bevacizumab at the investigator's discretion.

Interventions

• Biological Pembrolizumab
  Intravenous (IV) Infusion
• Biological Sacituzumab Tirumotecan
  IV Infusion
• Biological Bevacizumab
  IV Infusion
• Drug Paclitaxel
  IV Infusion
• Drug Cisplatin
  IV Infusion
• Drug Carboplatin
  IV Infusion
• Drug Rescue Medications
  Participants will receive the following rescue medications prior to sac-TMT infusion, per approved product label: histamine-1 receptor antagonist, histamine-2 receptor antagonist, acetaminophen or equivalent, and dexamethasone or equivalent, prophylactic steroid mouthwash (dexamethasone or equivalent), and granulocyte colony-stimulating factor (G-CSF).

Primary outcome measures

• Part 1 Safety Run-in: Number of Participants Who Experience One or More Adverse Events (AEs) [Time frame: Up to approximately 69 months]
• Part 1 Safety Run-in: Number of Participants Who Discontinue Study Treatment Due to an AE [Time frame: Up to approximately 66 months]
• Part 2 Maintenance Treatment: Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [Time frame: Up to approximately 48 months]
• Part 2 Maintenance Treatment: Overall Survival (OS) [Time frame: Up to approximately 60 months]

Secondary outcome measures (7)

• Part 2 Maintenance Treatment: Progression-free Survival 2 (PFS2) as Assessed by the Investigator [Time frame: Up to approximately 60 months]
• Part 2 Maintenance Treatment: Number of Participants Who Experience One or More AEs [Time frame: Up to approximately 64 months]
• Part 2 Maintenance Treatment: Number of Participants Who Discontinue Study Treatment Due to an AE [Time frame: Up to approximately 61 months]
• Part 2 Maintenance Treatment: Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status and Quality of Life Combined Score [Time frame: Baseline and up to approximately 58 months]
• Part 2 Maintenance Treatment: Change from Baseline in EORTC QLQ-C30 Physical Functioning Combined Score [Time frame: Baseline and up to approximately 58 months]
• Part 2 Maintenance Treatment: Change from Baseline in EORTC QLQ-C30 Role Functioning Combined Score [Time frame: Baseline and up to approximately 58 months]
• Part 2 Maintenance Treatment: Change from Baseline in EORTC Quality of Life Questionnaire-Cervical Cancer Module (QLQ-CX24) Combined Score [Time frame: Baseline and up to approximately 58 months]

Eligibility criteria

The main inclusion criteria include but are not limited to the following:

• Has a histologically confirmed diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of cervix
• Has persistent, recurrent, or newly diagnosed metastatic (International Federation of Gynecology and Obstetrics \[FIGO\]-2028 Stage IVB) cervical cancer that is not amenable to curative treatment (surgery and/or radiation)
• If infected with human immunodeficiency virus (HIV), has well controlled HIV on antiretroviral therapy
• If positive for hepatitis B surface antigen, has received hepatitis B virus (HBV) antiviral therapy and has undetectable HBV viral load
• If has a history of hepatitis C virus (HCV) infection, has undetectable HCV viral load
• Has an Eastern Cooperative Oncology Group performance status of 0 or 1
• Has tumor programmed cell death ligand 1 expression of combined positive score ≥1

The main exclusion criteria include but are not limited to the following:

• Has HIV infection with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• 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 (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
• Has received prior systemic anticancer therapy other than what is specified in this protocol
• Is currently receiving a strong inducer/inhibitor of cytochrome P450 3A4 that cannot be discontinued for the duration of treatment with sac-TMT
• Has a diagnosis of immunodeficiency
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known active central nervous system metastases and/or carcinomatous meningitis
• Has active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
• Has a history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids, has current pneumonitis/ILD, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments
• Has a history of stem cell/solid organ transplant
• Has not adequately recovered from major surgery or has ongoing surgical complications

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 · 19 centers

• Florida Cancer Specialists - South ( Site 7001) — Fort Myers
• Mount Sinai Braman Comprehensive Cancer Center ( Site 5043) — Miami Beach
• Mount Sinai Comprehensive Cancer Center ( Site 6000) — Miami Beach
• Florida Cancer Specialists - East ( Site 7000) — West Palm Beach
• Winship Cancer Institute of Emory University ( Site 5005) — Atlanta
• Nancy N. & J.C. Lewis Cancer and Research Pavillion - Research Department ( Site 6005) — Savannah
• TRIALS 365 ( Site 6008) — Shreveport
• Minnesota Oncology Hematology, PA ( Site 8003) — Edina
• … and 11 more centers

Japan · 17 centers

Center list to be confirmed — check the primary protocol.

Italy · 10 centers

Center list to be confirmed — check the primary protocol.

Brazil · 8 centers

• Hospital Araújo Jorge ( Site 0518) — Goiânia
• Liga Norte Riograndense Contra o Câncer ( Site 0513) — Natal
• Irmandade da Santa Casa de Misericordia de Porto Alegre ( Site 0514) — Porto Alegre
• Hospital São Lucas da PUCRS ( Site 0516) — Porto Alegre
• Fundação Pio XII - Hospital de Câncer de Barretos ( Site 0511) — Barretos
• Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto ( Site 0512) — São José do Rio Preto
• IBCC - Instituto Brasileiro de Controle do Câncer ( Site 0517) — São Paulo
• Instituto Nacional de Câncer - INCA ( Site 0515) — Rio de Janeiro

Canada · 8 centers

• Nova Scotia Cancer Centre ( Site 0617) — Halifax
• London Health Sciences Centre ( Site 0613) — London
• Sunnybrook Research Institute ( Site 0605) — Toronto
• Princess Margaret Cancer Centre ( Site 0601) — Toronto
• Centre Hospitalier de l'Université de Montréal ( Site 0616) — Montreal
• McGill University Health Centre ( Site 0602) — Montreal
• Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésu — Québec
• CIUSSS de l Estrie Centre Hospitalier Universitaire de Sherbrooke ( Site 0604) — Sherbrooke

Argentina · 7 centers

• Centro de Oncología e Investigación de Buenos Aires ( Site 0107) — Berazategui
• Instituto de Investigaciones Clinicas Mar del Plata ( Site 0105) — Mar del Plata
• Fundación Respirar ( Site 0101) — Belgrano
• Instituto Misionero del Cancer ( Site 0112) — Posadas
• Instituto de Oncologia de Rosario ( Site 0104) — Rosario
• Hospital Provincial del Centenario ( Site 0106) — Rosario
• Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0111) — La Rioja

France · 7 centers

• CHU Strasbourg-Hautepierre ( Site 1207) — Strasbourg
• CHRU de Brest-Institut de cancérologie et d'Hématologie ( Site 1202) — Brest
• Centre François Baclesse ( Site 1201) — Caen
• Pôle Santé Léonard de Vinci ( Site 1209) — Chambray-lès-Tours
• Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest ( S — Bordeaux
• LBM ONCOPOLE CLAUDIUS REGAUD ( Site 1203) — Toulouse
• Hopital Europeen Georges Pompidou ( Site 1210) — Paris

Spain · 7 centers

Center list to be confirmed — check the primary protocol.

Chile · 6 centers

• CIDO SpA-Oncology ( Site 0708) — Temuco
• IC La Serena Research ( Site 0710) — La Serena
• FALP ( Site 0701) — Santiago
• Pontificia Universidad Catolica de Chile-CICUC ( Site 0706) — Santiago
• Bradfordhill ( Site 0702) — Santiago
• ONCOCENTRO APYS-ACEREY ( Site 0703) — Viña del Mar

Israel · 6 centers

Center list to be confirmed — check the primary protocol.

Mexico · 6 centers

Center list to be confirmed — check the primary protocol.

Belgium · 5 centers

• Antwerp University Hospital ( Site 0407) — Edegem
• Cliniques Universitaires Saint-Luc ( Site 0402) — Brussels
• Grand Hopital de Charleroi ( Site 0404) — Charleroi
• UZ Gent ( Site 0406) — Ghent
• UZ Leuven ( Site 0401) — Leuven

Colombia · 5 centers

• Clinica Somer ( Site 0903) — Rionegro
• Centro Cancerológico del Caribe (CECAC) ( Site 0906) — Barranquilla
• Instituto Nacional De Cancerologia ( Site 0909) — Bogotá
• Oncomédica S.A.S ( Site 0905) — Montería
• Oncólogos del Occidente S.A.S. ( Site 0908) — Pereira

Czechia · 5 centers

• Fakultní Nemocnice Brno ( Site 1003) — Brno
• Nemocnice AGEL Novy Jicin a.s. ( Site 1004) — Nový Jičín
• Fakultni nemocnice Ostrava ( Site 1005) — Ostrava
• Fakultni nemocnice Kralovske Vinohrady ( Site 1002) — Prague
• Vseobecna fakultni nemocnice v Praze-Gynekologicko-porodnicka klinika 1.LF a VFN ( Site 10 — Prague

South Africa · 5 centers

Center list to be confirmed — check the primary protocol.

South Korea · 5 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 5 centers

Center list to be confirmed — check the primary protocol.

Austria · 4 centers

• Medizinische Universitaet Wien ( Site 0302) — Vienna
• Medizinische Universitat Graz ( Site 0303) — Graz
• Medizinische Universitaet Innsbruck ( Site 0301) — Innsbruck
• Uniklinikum Salzburg Landeskrankenhaus ( Site 0304) — Salzburg

Poland · 4 centers

Center list to be confirmed — check the primary protocol.

Thailand · 4 centers

Center list to be confirmed — check the primary protocol.

Greece · 3 centers

• Alexandra General Hospital of Athens-ONCOLOGY DEPT. ( Site 1401) — Athens
• Aretaieio Hospital Oncology Unit ( Site 1402) — Athens
• ATTIKON GENERAL UNIVERSITY HOSPITAL ( Site 1403) — Chaïdári

Ireland · 3 centers

Center list to be confirmed — check the primary protocol.

Sweden · 3 centers

Center list to be confirmed — check the primary protocol.

Hungary · 2 centers

• Országos Onkológiai Intézet ( Site 1603) — Budapest
• Debreceni Egyetem Klinikai Kozpont ( Site 1601) — Debrecen

India · 2 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 2 centers

Center list to be confirmed — check the primary protocol.

Germany · 1 center

• Universitaetsklinikum Jena ( Site 1303) — Jena

Identifiers

NCT: NCT07216703 · 2870-036 · U1111-1319-9926 · 2025-521514-26-00 · MK-2870-036 · TroFuse-036 · GOG-3123 · ENGOT-cx22 · jRCT2031250604

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗