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)
- Conditions
- Cervical Cancer
- Interventions
- Registration Number
- NCT07216703
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 1023
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 Safety Run-in: Sac-TMT + Pembrolizumab + Bevacizumab Pembrolizumab Participants will receive sac-TMT 4 mg/kg every 2 weeks (q2w) and pembrolizumab 400 mg every 6 weeks (q6w) for up to 14 cycles (up to approximately 19 months). Bevacizumab 15 mg/kg every 3 weeks (q3w) will be administered until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 1 Safety Run-in: Sac-TMT + Pembrolizumab + Bevacizumab Sacituzumab Tirumotecan Participants will receive sac-TMT 4 mg/kg every 2 weeks (q2w) and pembrolizumab 400 mg every 6 weeks (q6w) for up to 14 cycles (up to approximately 19 months). Bevacizumab 15 mg/kg every 3 weeks (q3w) will be administered until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 1 Safety Run-in: Sac-TMT + Pembrolizumab + Bevacizumab Bevacizumab Participants will receive sac-TMT 4 mg/kg every 2 weeks (q2w) and pembrolizumab 400 mg every 6 weeks (q6w) for up to 14 cycles (up to approximately 19 months). Bevacizumab 15 mg/kg every 3 weeks (q3w) will be administered until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 1 Safety Run-in: Sac-TMT + Pembrolizumab + Bevacizumab Rescue Medications Participants will receive sac-TMT 4 mg/kg every 2 weeks (q2w) and pembrolizumab 400 mg every 6 weeks (q6w) for up to 14 cycles (up to approximately 19 months). Bevacizumab 15 mg/kg every 3 weeks (q3w) will be administered until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 2: Sac-TMT + Pembrolizumab +/- Bevacizumab Pembrolizumab During induction treatment, participants will receive pembrolizumab 200 mg q3w, paclitaxel 175 mg/m\^2 q3w, and cisplatin 50 mg/m\^2 q3w (or carboplatin area under the curve \[AUC\]5 mg/mL/min q3w). Participants may also receive bevacizumab 15 mg/kg q3w at the investigator's discretion. Each cycle will be 3 weeks long and treatment will continue for up to 6 cycles (up to approximately 4 months). During maintenance treatment, participants will receive sac-TMT 4 mg/kg q2w and pembrolizumab 400 mg q6w for up to 14 cycles (up to approximately 19 months). Participants may also receive bevacizumab 15 mg/kg q3w, at the investigator's discretion, until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 2: Sac-TMT + Pembrolizumab +/- Bevacizumab Sacituzumab Tirumotecan During induction treatment, participants will receive pembrolizumab 200 mg q3w, paclitaxel 175 mg/m\^2 q3w, and cisplatin 50 mg/m\^2 q3w (or carboplatin area under the curve \[AUC\]5 mg/mL/min q3w). Participants may also receive bevacizumab 15 mg/kg q3w at the investigator's discretion. Each cycle will be 3 weeks long and treatment will continue for up to 6 cycles (up to approximately 4 months). During maintenance treatment, participants will receive sac-TMT 4 mg/kg q2w and pembrolizumab 400 mg q6w for up to 14 cycles (up to approximately 19 months). Participants may also receive bevacizumab 15 mg/kg q3w, at the investigator's discretion, until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 2: Sac-TMT + Pembrolizumab +/- Bevacizumab Bevacizumab During induction treatment, participants will receive pembrolizumab 200 mg q3w, paclitaxel 175 mg/m\^2 q3w, and cisplatin 50 mg/m\^2 q3w (or carboplatin area under the curve \[AUC\]5 mg/mL/min q3w). Participants may also receive bevacizumab 15 mg/kg q3w at the investigator's discretion. Each cycle will be 3 weeks long and treatment will continue for up to 6 cycles (up to approximately 4 months). During maintenance treatment, participants will receive sac-TMT 4 mg/kg q2w and pembrolizumab 400 mg q6w for up to 14 cycles (up to approximately 19 months). Participants may also receive bevacizumab 15 mg/kg q3w, at the investigator's discretion, until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 2: Sac-TMT + Pembrolizumab +/- Bevacizumab Paclitaxel During induction treatment, participants will receive pembrolizumab 200 mg q3w, paclitaxel 175 mg/m\^2 q3w, and cisplatin 50 mg/m\^2 q3w (or carboplatin area under the curve \[AUC\]5 mg/mL/min q3w). Participants may also receive bevacizumab 15 mg/kg q3w at the investigator's discretion. Each cycle will be 3 weeks long and treatment will continue for up to 6 cycles (up to approximately 4 months). During maintenance treatment, participants will receive sac-TMT 4 mg/kg q2w and pembrolizumab 400 mg q6w for up to 14 cycles (up to approximately 19 months). Participants may also receive bevacizumab 15 mg/kg q3w, at the investigator's discretion, until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 2: Sac-TMT + Pembrolizumab +/- Bevacizumab Cisplatin During induction treatment, participants will receive pembrolizumab 200 mg q3w, paclitaxel 175 mg/m\^2 q3w, and cisplatin 50 mg/m\^2 q3w (or carboplatin area under the curve \[AUC\]5 mg/mL/min q3w). Participants may also receive bevacizumab 15 mg/kg q3w at the investigator's discretion. Each cycle will be 3 weeks long and treatment will continue for up to 6 cycles (up to approximately 4 months). During maintenance treatment, participants will receive sac-TMT 4 mg/kg q2w and pembrolizumab 400 mg q6w for up to 14 cycles (up to approximately 19 months). Participants may also receive bevacizumab 15 mg/kg q3w, at the investigator's discretion, until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 2: Sac-TMT + Pembrolizumab +/- Bevacizumab Carboplatin During induction treatment, participants will receive pembrolizumab 200 mg q3w, paclitaxel 175 mg/m\^2 q3w, and cisplatin 50 mg/m\^2 q3w (or carboplatin area under the curve \[AUC\]5 mg/mL/min q3w). Participants may also receive bevacizumab 15 mg/kg q3w at the investigator's discretion. Each cycle will be 3 weeks long and treatment will continue for up to 6 cycles (up to approximately 4 months). During maintenance treatment, participants will receive sac-TMT 4 mg/kg q2w and pembrolizumab 400 mg q6w for up to 14 cycles (up to approximately 19 months). Participants may also receive bevacizumab 15 mg/kg q3w, at the investigator's discretion, until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 2: Sac-TMT + Pembrolizumab +/- Bevacizumab Rescue Medications During induction treatment, participants will receive pembrolizumab 200 mg q3w, paclitaxel 175 mg/m\^2 q3w, and cisplatin 50 mg/m\^2 q3w (or carboplatin area under the curve \[AUC\]5 mg/mL/min q3w). Participants may also receive bevacizumab 15 mg/kg q3w at the investigator's discretion. Each cycle will be 3 weeks long and treatment will continue for up to 6 cycles (up to approximately 4 months). During maintenance treatment, participants will receive sac-TMT 4 mg/kg q2w and pembrolizumab 400 mg q6w for up to 14 cycles (up to approximately 19 months). Participants may also receive bevacizumab 15 mg/kg q3w, at the investigator's discretion, until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 2: Pembrolizumab +/- Bevacizumab Pembrolizumab During induction treatment, participants will receive pembrolizumab 200 mg q3w, paclitaxel 175 mg/m\^2 q3w, and cisplatin 50 mg/m\^2 q3w (or carboplatin AUC5 mg/mL/min q3w). Participants may also receive bevacizumab 15 mg/kg q3w at the investigator's discretion. Each cycle will be 3 weeks long and treatment will continue for up to 6 cycles (up to approximately 4 months). During maintenance treatment, participants will receive pembrolizumab 400 mg q6w for up to 14 cycles (up to approximately 19 months). Participants may also receive bevacizumab 15 mg/kg q3w, at the investigator's discretion, until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 2: Pembrolizumab +/- Bevacizumab Bevacizumab During induction treatment, participants will receive pembrolizumab 200 mg q3w, paclitaxel 175 mg/m\^2 q3w, and cisplatin 50 mg/m\^2 q3w (or carboplatin AUC5 mg/mL/min q3w). Participants may also receive bevacizumab 15 mg/kg q3w at the investigator's discretion. Each cycle will be 3 weeks long and treatment will continue for up to 6 cycles (up to approximately 4 months). During maintenance treatment, participants will receive pembrolizumab 400 mg q6w for up to 14 cycles (up to approximately 19 months). Participants may also receive bevacizumab 15 mg/kg q3w, at the investigator's discretion, until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 2: Pembrolizumab +/- Bevacizumab Paclitaxel During induction treatment, participants will receive pembrolizumab 200 mg q3w, paclitaxel 175 mg/m\^2 q3w, and cisplatin 50 mg/m\^2 q3w (or carboplatin AUC5 mg/mL/min q3w). Participants may also receive bevacizumab 15 mg/kg q3w at the investigator's discretion. Each cycle will be 3 weeks long and treatment will continue for up to 6 cycles (up to approximately 4 months). During maintenance treatment, participants will receive pembrolizumab 400 mg q6w for up to 14 cycles (up to approximately 19 months). Participants may also receive bevacizumab 15 mg/kg q3w, at the investigator's discretion, until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 2: Pembrolizumab +/- Bevacizumab Cisplatin During induction treatment, participants will receive pembrolizumab 200 mg q3w, paclitaxel 175 mg/m\^2 q3w, and cisplatin 50 mg/m\^2 q3w (or carboplatin AUC5 mg/mL/min q3w). Participants may also receive bevacizumab 15 mg/kg q3w at the investigator's discretion. Each cycle will be 3 weeks long and treatment will continue for up to 6 cycles (up to approximately 4 months). During maintenance treatment, participants will receive pembrolizumab 400 mg q6w for up to 14 cycles (up to approximately 19 months). Participants may also receive bevacizumab 15 mg/kg q3w, at the investigator's discretion, until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long. Part 2: Pembrolizumab +/- Bevacizumab Carboplatin During induction treatment, participants will receive pembrolizumab 200 mg q3w, paclitaxel 175 mg/m\^2 q3w, and cisplatin 50 mg/m\^2 q3w (or carboplatin AUC5 mg/mL/min q3w). Participants may also receive bevacizumab 15 mg/kg q3w at the investigator's discretion. Each cycle will be 3 weeks long and treatment will continue for up to 6 cycles (up to approximately 4 months). During maintenance treatment, participants will receive pembrolizumab 400 mg q6w for up to 14 cycles (up to approximately 19 months). Participants may also receive bevacizumab 15 mg/kg q3w, at the investigator's discretion, until a treatment discontinuation criterion is met. Each cycle will be 6 weeks long.
- Primary Outcome Measures
Name Time Method Part 1 Safety Run-in: Number of Participants Who Experience One or More Adverse Events (AEs) Up to approximately 71 months 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.
Part 1 Safety Run-in: Number of Participants Who Discontinue Study Treatment Due to an AE Up to approximately 68 months 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.
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) Up to approximately 48 months PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first, as assessed by RECIST 1.1 as evaluated by BICR. PD is defined as ≥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 ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.
Part 2 Maintenance Treatment: Overall Survival (OS) Up to approximately 60 months OS is defined as time from randomization to death due to any cause. OS will be presented.
- Secondary Outcome Measures
Name Time Method Part 2 Maintenance Treatment: Progression-free Survival 2 (PFS2) as Assessed by the Investigator Up to approximately 60 months PFS2 is defined as the time from randomization to the documented subsequent objective disease progression after initiation of new anticancer therapy or death due to any cause, whichever occurs first. PFS2 as assessed by the investigator will be presented.
Part 2 Maintenance Treatment: Number of Participants Who Experience One or More AEs Up to approximately 64 months 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.
Part 2 Maintenance Treatment: Number of Participants Who Discontinue Study Treatment Due to an AE Up to approximately 61 months 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.
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 Baseline and up to approximately 58 months EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and QoL ("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). The combined score of GHS and QoL is computed by averaging the raw scores of the 2 questions and then applying a linear transformation to standardize the average score, so that the combined score ranges from 0 to 100. A higher score indicates a better outcome. The change from baseline in the EORTC QLQ-C30 GHS and QoL combined score will be presented.
Part 2 Maintenance Treatment: Change from Baseline in EORTC QLQ-C30 Physical Functioning Combined Score Baseline and up to approximately 58 months EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1 = Not at All to 4 = Very Much). The combined score is computed by averaging the raw scores of the 5 questions and then applying a linear transformation to standardize the average score, so that the combined score ranges from 0 to 100. A higher score indicates a better outcome. The change from baseline in the EORTC QLQ-C30 physical functioning combined score will be presented.
Part 2 Maintenance Treatment: Change from Baseline in EORTC QLQ-C30 Role Functioning Combined Score Baseline and up to approximately 58 months EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 2 questions about their role functioning are scored on a 4-point scale (1 = Not at All to 4 = Very Much). The combined score is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined score ranges from 0 to 100. A higher score indicates a better outcome. The change from baseline in the EORTC QLQ-C30 role functioning combined score will be presented.