NCT06459180 - 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) | Crick

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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 other histological subtypes of cervical cancer apart from squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma (eg, carcinosarcoma), or has a diagnosis of nonepithelial cancer (eg, sarcoma, neuroendocrine tumors) of the cervix. * 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

Outcomes

Primary Outcomes

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.

Time frame: Up to approximately 51 months

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.

Time frame: Up to approximately 51 months

Number of Participants Discontinuing Study Treatment Due to an AE in Sacituzumab Tirumotecan Run-in

Time frame: Up to approximately 51 months

Overall Survival (OS) in Phase 3 Portion

OS is defined as the time from randomization to death due to any cause.

Time frame: Up to approximately 43 months

Secondary Outcomes

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.

Time frame: Up to approximately 43 months

ORR in Phase 3 Portion

Time frame: Up to approximately 43 months

Duration of Response (DOR) in Phase 3 Portion

For participants who demonstrate CR (CR: disappearance of all target lesions) or PR (PR: at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to 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. DOR will be presented as assessed by BICR and analyzed by the Kaplan-Meier method for censored data.

Time frame: Up to approximately 43 months

Number of Participants Experiencing One or More AEs in Phase 3 Portion

Time frame: Up to approximately 51 months

Number of Participants Discontinuing Study Treatment Due to an AE in Phase 3 Portion

Time frame: Up to approximately 51 months

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.

Time frame: Baseline and up to approximately 51 months

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.

Time frame: Baseline and up to approximately 51 months

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.

Time frame: Baseline and up to approximately 51 months

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.

Time frame: Baseline and up to approximately 51 months

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)

Overview

Conditions

Interventions

Eligibility

Locations (240)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts