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)

Cervical Cancer Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06459180
• Other study ID #: 2870-020
• Secondary ID: MK-2870-020TroFu
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 5, 2024
• Est. completion date: October 23, 2028

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will have two phases: a sacituzumab tirumotecan safety run-in and a Phase 3 portion. The safety run-in phase will be used to evaluate the efficacy and safety of sacituzumab tirumotecan at the dose for evaluation in the Phase 3 portion. The purpose of this study is to compare the efficacy and safety of sacituzumab tirumotecan versus treatment of physician's choice as second-line treatment for participants with recurrent or metastatic cervical cancer in the Phase 3 portion. The primary study hypotheses are that, in the Phase 3 portion, sacituzumab tirumotecan results in a superior overall survival compared to TPC in participants with high trophoblast cell surface antigen 2 (TROP2) expression level and in all participants.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 686
• Est. completion date: October 23, 2028
• Est. primary completion date: October 23, 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has histologically-confirmed diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix
• Has recurrent or metastatic cervical cancer
• 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 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 histologically-confirmed diagnosis of glassy cell carcinoma variant, adenoid cystic carcinoma, adenoid basal carcinoma, neuroendocrine tumors, carcinoid, atypical carcinoid, small-carcinoma, large-cell neuroendocrine carcinoma, or undifferentiated carcinoma
• 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

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Biological:
• Sacituzumab Tirumotecan
IV infusion

Drug:
• Pemetrexed
IV infusion

Biological:
• Tisotumab Vedotin
IV infusion

Drug:
• Topotecan
IV infusion
• Vinorelbine
IV infusion
• Gemcitabine
IV infusion
• Irinotecan
IV infusion

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) in Sacituzumab Tirumotecan Run-in	ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.	Up to approximately 51 months
Primary	Number of Participants Experiencing One or More Adverse Events (AEs) in Sacituzumab Tirumotecan Run-in	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 51 months
Primary	Number of Participants Discontinuing Study Treatment Due to an AE in Sacituzumab Tirumotecan Run-in	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 51 months
Primary	Overall Survival (OS) in Phase 3 Portion	OS is defined as the time from randomization to death due to any cause.	Up to approximately 43 months
Secondary	Progression-free Survival (PFS) in Phase 3 Portion	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.	Up to approximately 43 months
Secondary	ORR in Phase 3 Portion	ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by BICR in the Phase 3 portion will be presented.	Up to approximately 43 months
Secondary	Number of Participants Experiencing One or More AEs in Phase 3 Portion	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 51 months
Secondary	Number of Participants Discontinuing Study Treatment Due to an AE in Phase 3 Portion	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 51 months
Secondary	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	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher value indicates a better level of function. TTD in Global Health Status (GHS)/Quality of Life (QoL) is defined as the time from baseline to the first onset of a =10-point decrease from baseline in combined GHS/QoL score. The TTD in GHS/QoL (Items 29 and 30) combined score will be reported.	Baseline and up to approximately 51 months
Secondary	Change from Baseline in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score in Phase 3 Portion	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher value indicates a better level of function. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be reported.	Baseline and up to approximately 51 months
Secondary	Change from Baseline in EORTC QLQ-C30 Physical Functioning Score in Phase 3 Portion	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better level of physical functioning.	Baseline and up to approximately 51 months
Secondary	Change from Baseline in EORTC QLQ-C30 Role Functioning Score in Phase 3 Portion	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "Were you limited in doing either your work or other daily activities during the past week?" and " Were you limited in pursuing your hobbies or other leisure time activities during the past week?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores indicate a more impaired level of role functioning. Change from baseline in the role functioning score will be presented.	Baseline and up to approximately 51 months

External Links

•   Merck Clinical Trials Information