The purpose of this study is to see how well mocertatug rezetecan (Mo-Rez) in combination with physician's choice of immunotherapy (dostarlimab or pembrolizumab) works as maintenance therapy in participants with advanced or recurrent endometrial cancer (EC) compared with the physician's choice of immunotherapy (dostarlimab or pembrolizumab) alone, which represents the current standard of care. The study will also assess whether the drug combination is safe and tolerated well by participants compared to standard of care and will help us better understand its impact on Health-Related Quality of Life of participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
610
Mocertatug rezetecan will be administered
Dostarlimab will be administered
Pembrolizumab will be administered
Progression free survival (PFS) by BICR assessment
PFS is defined as the time from the date of randomization to the date of first documented Progressive Disease (PD) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) by Blinded independent central review (BICR) assessment or death from any cause, whichever occurs first
Time frame: Up to approximately 143 weeks
Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of death due to any cause
Time frame: Up to approximately 260 weeks
PFS by investigator assessment
PFS is defined as the time from the date of randomization to the date of first documented PD per RECIST 1.1 by investigator assessment or death from any cause, whichever occurs first
Time frame: Up to approximately 143 weeks
Objective response rate (ORR) by investigator assessment
ORR is defined as the percentage of participants with best overall response of either complete response (CR) or partial response (PR) per RECIST 1.1 by investigator assessment
Time frame: Up to approximately 260 weeks
ORR by BICR assessment
ORR is defined as the percentage of participants with best overall response of either CR or PR per RECIST 1.1 by BICR assessment
Time frame: Up to approximately 260 weeks
Duration of Response (DOR) by investigator assessment
DOR is defined as the time from the date of first documented objective response (CR or PR) to the date of first documented PD per RECIST 1.1 by investigator assessment or death from any cause, whichever comes first
Time frame: Up to approximately 260 weeks
DOR by BICR assessment
DOR is defined as the time from the date of first documented objective response (CR or PR) to the date of first documented PD per RECIST 1.1 by BICR assessment or death from any cause, whichever comes first
Time frame: Up to approximately 260 weeks
Progression Free Survival on subsequent line of therapy (PFS2)
PFS2 is defined as the time from the date of randomization to the date of first documented investigator-assessed clinical or radiographical progression following the first subsequent anticancer therapy and after the progression event used for PFS, or death from any cause, whichever occurs first
Time frame: Up to approximately 260 weeks
Time to first subsequent therapy or death (TFST)
TFST is defined as the time from the date of randomization to the date of initiation of subsequent therapy or death from any cause, whichever occurs first
Time frame: Up to approximately 260 weeks
Time to second subsequent therapy (TSST)
TSST is defined as the time from the date of randomization to the date of initiation of second subsequent therapy or death from any cause, whichever occurs first
Time frame: Up to approximately 260 weeks
Serum pharmacokinetic (PK) concentration of Mo-Rez (conjugated antibody and payload)
Time frame: Up to approximately 260 weeks
Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb) against Mo-Rez
Time frame: Up to approximately 260 weeks
Titers of ADA against Mo-Rez
Time frame: Up to approximately 260 weeks
Number of participants with Treatment-emergent adverse event (TEAEs), Adverse event of special interest (AESIs), Immune-mediated adverse event (imAEs) and Treatment-emergent serious adverse event (TESAEs)
Time frame: Up to approximately 260 weeks
Number of participants with TEAEs leading to dose modifications or study intervention discontinuation
Time frame: Up to approximately 260 weeks
Number of participants with changes in vital signs, laboratory tests (hematology and clinical chemistry), and Electrocardiogram (ECG)
Time frame: Up to approximately 260 weeks
Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) score
The EORTC QLQ-C30 includes 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies. Participants responses on these items are averaged and then transformed to scores ranging from 0 to 100. For items related to function and global health status, a higher score indicates better functioning or a better overall state of health, while, for symptom-related items, a higher score denotes more severe symptoms.
Time frame: Up to approximately 260 weeks
Change from baseline in EORTC QLQ- Endometrial Cancer Module (EN24) score
The EORTC QLQ-EN24 includes a 24-item questionnaire for evaluating endometrial cancer-specific symptoms and concerns in participants of cancer clinical studies. Participants responses are averaged and then transformed to a score ranging from 0 to 100. For functional and global health items, a higher score indicates better functioning or a better overall state of health, while for symptom items, a higher score indicates more severe symptoms.
Time frame: Up to approximately 260 weeks
Time to deterioration (TTD) of EORTC QLQ-EN24
TTD is defined as the time from date of randomization to the first confirmed clinically meaningful deterioration on any of the domains of EORTC QLQ-EN24: lymphoedema, urological symptoms, gastrointestinal symptoms, and pain in back and pelvis
Time frame: Up to approximately 260 weeks
TTD of EORTC QLQ-C30
TTD is defined as the time from date of randomization to the first confirmed clinically meaningful deterioration on any of the domains of EORTC QLQ-C30: physical functioning, role functioning, and Global Health Status (GHS) /Quality of Life (QoL)
Time frame: Up to approximately 260 weeks
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