Neoplasms, Endometrial
Conditions
Keywords
Mocertatug rezetecan, Mo-Rez, GSK5733584, Dostarlimab, Pembrolizumab, Endometrial Cancer, Antibody-Drug Conjugate, BEHOLD-Endometrial02
Brief summary
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.
Interventions
Mocertatug rezetecan will be administered
DRUGDostarlimab
Dostarlimab will be administered
DRUGPembrolizumab
Pembrolizumab will be administered
Sponsors
GlaxoSmithKline
ENGOT, GOG, APGOT
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The independent central reviewer assessing primary outcome data will be masked (blinded) from participants treatment assignment.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is at least 18 years of age and the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the Informed consent form (ICF). * Has received 6 cycles of first-line therapy (i.e. induction therapy), consisting of platinum-based doublet chemotherapy (e.g., carboplatin/paclitaxel) with immune checkpoint inhibition as part of standard of care (either pembrolizumab or dostarlimab) or via trial Run-In (dostarlimab). Receipt of only 4 cycles of chemotherapy is permitted if chemotherapy was discontinued due to toxicity, provided that the participant received at least 12 weeks of immune checkpoint inhibitor therapy during the induction period. * Is able to commence C1D1 of study treatment within 3 - 9 weeks of the final dose of first-line therapy. * Is deemed suitable to continue with maintenance therapy with immune checkpoint inhibition (dostarlimab or pembrolizumab). * Demonstrates no clinical or radiographic progression of disease per investigator after the final dose of induction therapy. Final dose is defined as the last day that either platinum chemotherapy, taxane chemotherapy or immune checkpoint inhibition was given within the last cycle of induction therapy * Has histologically confirmed endometrial carcinoma including but not limited to endometrioid, serous, clear cell and endometrial carcinosarcoma. Mixed epithelial carcinomas are permitted. * Meets one of the following criteria: * Has newly diagnosed stage III disease \[2023 International Federation of Gynecology and Obstetrics (FIGO) staging\] with measurable residual disease \>1 cm after primary debulking surgery (incomplete cytoreduction). * Has newly diagnosed stage III disease (2023 FIGO staging) that is not suitable for primary debulking surgery with measurable disease. * Has newly diagnosed stage IV disease (2023 FIGO staging) and any residual disease status (measurable or non-measurable) following debulking surgery. Participants not suitable for primary debulking surgery are also permitted. * Has recurrent disease and is naïve to systemic anticancer therapy and any disease status (measurable or non-measurable). * Has recurrent disease after receiving prior neo-adjuvant/adjuvant systemic anticancer therapy and had a recurrence \>12 months after last dose of neo-adjuvant/adjuvant treatment. Participants with any disease status (measurable or non-measurable) are permitted. * Has a tumor demonstrating either Mismatch Repair proficient (MMRp) or Microsatellite stable (MSS). * Has provided a Formalin fixed, paraffin embedded (FFPE) tumor tissue sample sufficient for the central assessment of B7 homolog 4 protein (B7-H4) expression and MMR (if local MMRp/MSS test result(s) not available), with the result of B7-H4 expression testing available prior to date of randomization. * Is willing to use adequate contraception. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion criteria
* Mesenchymal tumors of the uterus (uterine sarcomas) and neuroendocrine uterine cancer. * Has a malignancy (except disease under study) that has progressed or required active treatment within 36 months prior to date of randomization except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas. * Any evidence of current Interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis. * Has experienced any of the following with prior immunotherapy: any imAE ≥ Grade 3, immune-mediated severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson syndrome \[SJS\], Toxic Epidermal Necrolysis \[TEN\], or Drug Reaction with Eosinophilia and Systemic Symptoms \[DRESS\] syndrome, or myocarditis of any grade. * Has ongoing adverse reaction(s) from prior therapy that has(have) not recovered to ≤ Grade 1 or to the baseline status preceding prior therapy, excluding alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 neuropathy, or adverse reactions that the investigator, with the agreement of the sponsor, considers to be not clinically relevant for the tolerability of study intervention in the current clinical study. * Has had any major surgery within 28 days prior to date of C1D1 or received focal radiotherapy within 21 days prior to date of C1D1. * Has received treatment with an investigational agent within 30 days prior to C1D1. * Has received prior therapy with topoisomerase I inhibitors (e.g. irinotecan or topotecan) or Antibody-Drug Conjugate (ADC)with a topoisomerase I inhibitor warhead, B7-H4 targeted therapy, or immune checkpoint inhibitor. * Has received treatment with inhibitors of P-glycoprotein (P-gp) or Breast cancer resistant protein (BCRP), or OATP1B1/1B3 transporterswithin 7 days prior to the date of C1D1. Inducers of P-gp should be discontinued for at least 14 days prior to the date of C1D1. * Has received any transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including Granulocyte-Colony Stimulating Factor \[G-CSF\], Granulocyte-Macrophage Colony-Stimulating Factor \[GM-CSF\], or recombinant erythropoietin) within 14 days prior to C1D1. * Has an Alanine aminotransferase (ALT) value \>2.5 × Upper limit of normal (ULN) or for participants with documented liver metastases/tumor infiltration has an ALT value \>5 × ULN. * Has a total bilirubin value \>1.5 × ULN. * Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice. Participants who exhibit these signs or symptoms as a result of the malignancy under investigation and whose conditions are deemed adequately controlled by the investigator may be eligible for inclusion. * Has Corrected QT interval (QTc) \>470 milliseconds (msec). * Has a history of symptomatic pericarditis of any cause within 6 months prior to screening or evidence of cardiac abnormalities within 12 months prior to screening such as serious, uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities. * Has any active renal condition (e.g., infection, requirement for dialysis, or any other significant renal condition that could affect the participant's safety).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) by BICR assessment | Up to approximately 143 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival on subsequent line of therapy (PFS2) | Up to approximately 260 weeks | 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 to first subsequent therapy or death (TFST) | Up to approximately 260 weeks | 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 to second subsequent therapy (TSST) | Up to approximately 260 weeks | 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 |
| Serum pharmacokinetic (PK) concentration of Mo-Rez (conjugated antibody and payload) | Up to approximately 260 weeks | — |
| Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb) against Mo-Rez | Up to approximately 260 weeks | — |
| Titers of ADA against Mo-Rez | 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) | Up to approximately 260 weeks | — |
| Number of participants with TEAEs leading to dose modifications or study intervention discontinuation | Up to approximately 260 weeks | — |
| Number of participants with changes in vital signs, laboratory tests (hematology and clinical chemistry), and Electrocardiogram (ECG) | Up to approximately 260 weeks | — |
| Overall Survival (OS) | Up to approximately 260 weeks | OS is defined as the time from the date of randomization to the date of death due to any cause |
| PFS by investigator assessment | Up to approximately 143 weeks | 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 |
| Objective response rate (ORR) by investigator assessment | Up to approximately 260 weeks | 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 |
| ORR by BICR assessment | Up to approximately 260 weeks | ORR is defined as the percentage of participants with best overall response of either CR or PR per RECIST 1.1 by BICR assessment |
| Duration of Response (DOR) by investigator assessment | Up to approximately 260 weeks | 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 |
| Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) score | Up to approximately 260 weeks | 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. |
| Change from baseline in EORTC QLQ- Endometrial Cancer Module (EN24) score | Up to approximately 260 weeks | 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 to deterioration (TTD) of EORTC QLQ-EN24 | Up to approximately 260 weeks | 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 |
| DOR by BICR assessment | Up to approximately 260 weeks | 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 |
| TTD of EORTC QLQ-C30 | Up to approximately 260 weeks | 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) |
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed