Clinical study comparing MK-2870 with standard treatment in patients with cervical cancer that has spread or returned after treatment
Résumé de l'étude
The main objective of this study is to investigate the safety and efficacy of MK-2870 compared to 6 standard therapies in patients with cervical cancer that has returned during or after a previous treatment or has spread to other parts of the body. MK-2870 is an experimental drug consisting of a monoclonal antibody combined with a toxin (KL610023), also known as antibody-drug conjugate or ADC. Antibodies are proteins produced by the immune system that help the body fight foreign substances such as bacteria or viruses, as well as tumors. Monoclonal antibodies bind to specific targets on cells. MK-2870 binds to a target on certain cancer cells known as trophoblast antigen 2 (TROP2). Through this binding, the toxin (KL610023) can damage these cancer cells. MK-2870 is not yet approved in Switzerland and is being tested in various studies for the treatment of different diseases. The following drugs may be used as standard therapies in this global study (depending on the standard therapy at the respective study center): the chemotherapies Pemetrexed, Topotecan, Vinorelbine, Gemcitabine, or Irinotecan, or Tisotumab Vedotin, which, like MK-2870, is a combination of antibody and toxin. In the study described here, approximately 686 participants are expected to take part worldwide, including about 8 from Switzerland. The total duration of the study is approximately 4.5 years.
(BASEC)
Intervention étudiée
The study begins with Part 1:
20 participants will be screened for study eligibility for up to 28 days (this phase is called "screening"). Those who are eligible and wish to participate will receive MK-2870 as the study drug in this part.
Since MK-2870 has proven to be generally well tolerated as monotherapy in other tumor indications, Part 2 of the study follows without interruption, while the internal data monitoring committee reviews the efficacy and safety data from Part 1:
After a screening phase of up to 42 days, each eligible participant will be randomly assigned to receive either MK-2870 (Arm 1) or a standard therapy (Arm 2). The probability of being assigned to Arm 1 or 2 is equal, and both the participants and study doctors know which treatment is being administered.
MK-2870 will be administered as an intravenous infusion every two weeks at the study center.
The standard therapy in Arm 2 will be selected by the study doctor (one of 6 possible options). This will also be administered as an intravenous infusion at the center, with the number of center visits varying depending on the chosen therapy.
Treatment with MK-2870 or the standard therapy may continue as long as the cancer does not worsen, the medications are tolerated, no new cancer treatment is started, or the study doctor does not recommend stopping the medications.
After treatment is completed, participants will be followed for a certain period.
As part of study visits, various measures and examinations may be performed, such as imaging procedures like CT/MRI (computed tomography or magnetic resonance imaging), bone scans, or X-rays, heart examinations (such as electrocardiograms (ECG), MUGA scans (“multiple-gated acquisition” scan) or echocardiograms (ECHO)), collection of blood, urine, or tissue samples, physical examinations including checking vital signs (pulse, blood pressure, etc.), and answering questionnaires.
(BASEC)
Maladie en cours d'investigation
Worldwide, cervical cancer is the fourth most common cancer diagnosis and cause of cancer death in women. Cervical cancer is one of the most treatable types of cancer when detected early. The best way to detect cervical cancer early is through regular gynecological check-ups. When cervical cancer is diagnosed, there are several treatment options depending on the stage of the disease: surgical interventions such as conization (scraping of the cervix) or removal of the uterus, radiation therapy, chemotherapy, targeted therapy, or immunotherapy. However, for the treatment of persistent, recurrent, or metastatic (spread to other body parts) cervical cancer, the prognosis remains poor. Recently, Pembrolizumab in combination with platinum-based chemotherapy, with or without Bevacizumab, has become the first treatment option for patients whose tumors express PD-L1 (a certain surface protein), which accounts for about 90% of all patients. For tumors that do not express this protein, the standard treatment remains chemotherapy with or without Bevacizumab. Bevacizumab inhibits the formation of new blood vessels in tumors. However, not all patients with persistent, recurrent, or metastatic cervical cancer are suitable for treatment with Bevacizumab, for example in the presence of active bleeding, non-healing wounds, or occlusion of a blood vessel. Other treatment options after first-line therapy often have a poor risk-benefit profile with low response rates, which is why new therapeutic approaches and the development of new drugs are being researched.
(BASEC)
• Confirmed diagnosis of recurrent or metastatic cervical cancer • Disease progression during or after systemic platinum-based chemotherapy and receipt of anti-PD-1/anti-PD-L1 as part of a previous treatment • Radiologically evaluable disease (BASEC)
Critères d'exclusion
• Receipt of systematic second-line chemotherapy • Documented history of eye diseases (such as severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis or a corneal disease that prevents/delays corneal healing) • Uncontrolled significant cardiovascular disease or a disease of the blood vessels in the brain (BASEC)
Lieu de l’étude
Bâle, Berne
(BASEC)
Sponsor
MSD Merck Sharp & Dohme AG Luzern
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Klaudia Georgi
+41 (0)58 618 33 88
klaudia.georgi@cluttermsd.comMerck Sharp & Dohme LLC 126 East Lincoln Ave. P.O. Box 2000 07065 Rahway, New Jersey USA
(BASEC)
Informations générales
Merck Sharp & Dohme LLC,
1-888-577-8839
klaudia.georgi@cluttermsd.com(ICTRP)
Informations scientifiques
Merck Sharp & Dohme LLC,
1-888-577-8839
klaudia.georgi@cluttermsd.com(ICTRP)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale d'éthique de Berne
(BASEC)
Date d'approbation du comité d'éthique
13.08.2024
(BASEC)
Identifiant de l'essai ICTRP
NCT06459180 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
A Phase 3 Randomized, Active-controlled, Open-label, Multicenter Study to Compare the Efficacy and Safety of MK-2870 Monotherapy Versus Treatment of Physician’s Choice as Second-line Treatment for Participants with Recurrent or Metastatic Cervical Cancer (TroFuse-020/GOG-3101/ENGOT-cx20) (BASEC)
Titre académique
A Phase 3 Randomized, Active-controlled, Open-label, Multicenter Study to Compare the Efficacy and Safety of MK-2870 Monotherapy Versus Treatment of Physician's Choice as Second-line Treatment for Participants With Recurrent or Metastatic Cervical Cancer (TroFuse-020/GOG-3101/ENGOT-cx20) (ICTRP)
Titre public
A Study to Compare Sacituzumab Tirumotecan (MK-2870) Monotherapy Versus Treatment of Physician's Choice as Second-line Treatment for Participants With Recurrent or Metastatic Cervical Cancer (MK-2870-020/TroFuse-020/Gog-3101/ENGOT-cx20) (ICTRP)
Maladie en cours d'investigation
Cervical Cancer (ICTRP)
Intervention étudiée
Biological: Sacituzumab TirumotecanDrug: PemetrexedBiological: Tisotumab VedotinDrug: TopotecanDrug: VinorelbineDrug: GemcitabineDrug: Irinotecan (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Critères d'inclusion/exclusion
Inclusion Criteria:
- Has histologically-confirmed diagnosis of squamous cell carcinoma, adenosquamous
carcinoma, or adenocarcinoma of the cervix
- Must have recurrent or metastatic cervical cancer that has progressed on or after
treatment with 1 prior line of systemic platinum doublet chemotherapy (with or
without bevacizumab) AND must have received anti-PD-1/anti-PD-L1 therapy as part of
prior cervical cancer regimens
- Has measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST)
1.1, as assessed by the investigator. Lesions situated in a previously irradiated
area are considered measurable if progression has been shown in such lesions
- Is assigned female sex at birth, at least 18 years of age at the time of providing
the informed consent
- Has ECOG performance status of 0 or 1 within 7 days before allocation for the
Sacituzumab Tirumotecan Run-in or within 7 days before randomization for the Phase 3
portion
- Has provided tumor tissue (most recent sample is preferred) from a core or
excisional biopsy of a tumor lesion not previously irradiated
- HIV-infected participants must have well controlled human immunodeficiency virus
(HIV) on antiretroviral therapy (ART)
- Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if
they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks,
and have undetectable HBV viral load prior to allocation (Sacituzumab Tirumotecan
Run-in) or randomization (Phase 3 portion)
- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV
viral load is undetectable at screening
- Has adequate organ function
Exclusion Criteria:
- Has Grade =2 peripheral neuropathy
- Has 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.
- Received prior systemic anticancer therapy
- Received prior radiotherapy within 2 weeks of start of study intervention, or has
radiation-related toxicities, requiring corticosteroids
- Received a live or live-attenuated vaccine within 30 days before the first dose of
study intervention. Administration of killed vaccines is allowed
- Has histological subtypes of cervical cancer other than squamous cell carcinoma,
adenocarcinoma, or adenosquamous carcinoma (eg, carcinosarcoma) or nonepithelial
cancer (eg, sarcoma, neuroendocrine tumors)
- Known additional malignancy that is progressing or has required active treatment
within the past 3 years
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Active infection requiring systemic therapy
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric
Castleman's Disease
- Concurrent active Hepatitis B and active Hepatitis C virus infection
- Severe hypersensitivity (=Grade 3) to sacituzumab tirumotecan or treatment of
physician's choice (TPC) and/or any of their excipients, or other biologic therapy
- Participants who have not adequately recovered from major surgery or have ongoing
surgical complications
- Has a history of (noninfectious) pneumonitis/ILD that required steroids or has
current pneumonitis/ILD (ICTRP)
non disponible
Critères d'évaluation principaux et secondaires
Objective Response Rate (ORR) in Sacituzumab Tirumotecan Run-in;Number of Participants Experiencing One or More Adverse Events (AEs) in Sacituzumab Tirumotecan Run-in;Number of Participants Discontinuing Study Treatment Due to an AE in Sacituzumab Tirumotecan Run-in;Overall Survival (OS) in Phase 3 Portion (ICTRP)
Progression-free Survival (PFS) in Phase 3 Portion;ORR in Phase 3 Portion;Duration of Response (DOR) in Phase 3 Portion;Number of Participants Experiencing One or More AEs in Phase 3 Portion;Number of Participants Discontinuing Study Treatment Due to an AE in Phase 3 Portion;Time to First Deterioration (TTD) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score in Phase 3 Portion;Change from Baseline in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score in Phase 3 Portion;Change from Baseline in EORTC QLQ-C30 Physical Functioning Score in Phase 3 Portion;Change from Baseline in EORTC QLQ-C30 Role Functioning Score in Phase 3 Portion (ICTRP)
Date d'enregistrement
non disponible
Inclusion du premier participant
non disponible
Sponsors secondaires
European Network of Gynaecological Oncological Trial Groups (ENGOT);GOG Foundation (ICTRP)
Contacts supplémentaires
Medical Director;Toll Free Number, Trialsites@msd.com, 1-888-577-8839, Merck Sharp & Dohme LLC, (ICTRP)
ID secondaires
MK-2870-020, TroFuse-020, 2023-508323-12, U1111-1298-0563, GOG-3101, ENGOT-cx20, jRCT2031240201, 2870-020 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT06459180 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
non disponible