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)
NCT Number: NCT06459180
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Cervical Cancer
Interventions: BIOLOGICAL: Sacituzumab Tirumotecan|DRUG: Pemetrexed|BIOLOGICAL: Tisotumab Vedotin|DRUG: Topotecan|DRUG: Vinorelbine|DRUG: Gemcitabine|DRUG: Irinotecan
Sponsor: Merck Sharp & Dohme LLC
Collaborators: European Network of Gynaecological Oncological Trial Groups (ENGOT)|GOG Foundation
Sex: FEMALE
Age: ADULT, OLDER_ADULT
Enrollment: 686
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-24
Completion Date: 2028-10-23
Locations: Willis Knighton Medical Center ( Site 4101), Shreveport, Louisiana, 71103, United States|The Center of Hope ( Site 4106), Reno, Nevada, 89511, United States|Blacktown Hospital ( Site 3006), Sydney, New South Wales, 2148, Australia|Rambam Health Care Campus ( Site 2002), Haifa, 3109601, Israel|Edith Wolfson Medical Center ( Site 2003), Holon, 5810001, Israel|Hadassah Medical Center ( Site 2000), Jerusalem, 9112001, Israel|Severance Hospital, Yonsei University Health System ( Site 3402), Seoul, 03722, Korea, Republic of|Samsung Medical Center ( Site 3400), Seoul, 06351, Korea, Republic of|UPR Comprehensive Cancer Center-Comprehensive Cancer Center Hospital ( Site 0601), San Juan, 00935, Puerto Rico|University Hospital Basel-Gynecology & Gynecologic Oncology ( Site 2701), Basel, Basel-Stadt, 4031, Switzerland|Inselspital Bern-Oncology ( Site 2700), Berne, 3010, Switzerland

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.

Primary Outcome Measures: 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|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|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|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 Outcome Measures: 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|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|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., Up to approximately 43 months|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|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|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|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|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|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