Tumours, Gynecological
Conditions
Keywords
Solid Tumors, Mocertatug Rezetecan, Mo-Rez, GSK5733584, BEHOLD-2
Brief summary
Advanced solid tumors are cancers that have spread to other parts of the body. While many treatments exist, most people become resistant to them, and the cancer returns. Researchers are developing new treatments that combine different medicines for those who do not respond to single medicine. This study is looking at how safe and tolerable Mocertatug Rezetecan (Mo-Rez) is, how the body handles it, and how well it works when used with other cancer medicines. The study will include participants with advanced solid tumors who have either not responded to standard treatments or cannot tolerate them or have no available effective treatment.
Interventions
DRUGMo-Rez
Mo-Rez will be administered intravenously (IV).
DRUGDostarlimab
Dostarlimab will be administered IV.
DRUGBevacizumab
Bevacizumab will be administered IV.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must be 18 years of age inclusive or older, at the time of signing the informed consent, or the legal age of consent in the jurisdiction in which the study is taking place. * Participant capable of giving signed informed consent including compliance with the requirements and restrictions listed in the Informed consent form (ICF) and in this protocol. * Participants with pathologically confirmed advanced solid tumor specific for study Module (key local diagnostic molecular and/or immunophenotyping testing results/tumor cell phenotype results for confirmed diagnosis should be provided) with no more than 4 lines of prior systemic therapies. Please note: 1. Adjuvant +/- neoadjuvant considered one line of therapy 2. Maintenance therapy will be considered as part of the preceding line of therapy (i.e., not counted independently) 3. Unplanned addition or switching to a new drug in a different class is considered a separate line of therapy. If an agent in a regimen is switched to another agent in the same class due to toxicity or intolerance (e.g. hypersensitivity reaction) this is considered part of the same line (i.e. not counted independently). * Requirements for tumor tissue samples: Archival or fresh tumor tissue is required for retrospective central assessment of B7H4 expression by immunohistochemistry (IHC) and other biomarker analysis. The archival tumor tissue should be from the most recent procedure (ideally obtained after the last anti-cancer treatment). If an archival tissue is not available a new biopsy should be performed, and the newly obtained tissue provided. * Participants have at least one target lesion as assessed per RECIST 1.1. A target lesion is defined as a measurable lesion that has not undergone locoregional treatment such as irradiation or that has unequivocal progression following locoregional treatment, with the longest diameter of ≥ 10 millimeter (mm) at Baseline (for lymph node lesions, the short axis should be ≥ 15 mm). * Participants have a life expectancy of at least 12 weeks per investigator assessment based on disease burden and extent of supportive care needed. Inclusion criteria of participants under arm Module 1 (Mo-Rez +Dostarlimab) Endometrial Cancer Part 1A: a. Participants with histologically documented, advanced (metastatic and/or unresectable) or recurrent endometrial cancer who have failed in adequate standard treatments, do not have effective standard treatment or are intolerant to standard of care, and who are not candidates for further curative external radiotherapy or brachytherapy. Inclusion criteria of participants under arm Module 1 (Mo-Rez +Dostarlimab) Endometrial Cancer Part 1B: 1. Diagnosis of endometrial cancer with confirmed mismatch repair proficient (MMRp) or microsatellites stable (MSS) tumor status by local test. 2. Participants who have progressed on or are intolerant to at least 1 line of standard prior systemic therapy (including neoadjuvant or adjuvant as prior line), and who are not candidates for curative external radiotherapy or brachytherapy. Maintenance therapy will be considered part of the preceding line of therapy (i.e, not counted independently). Inclusion criteria of participants under arm Module 2 (Mo-Rez +/- Bevacizumab) Ovarian Cancer Part 2A: a. Participants with histologically or cytologically confirmed advanced epithelial ovarian cancer/fallopian tube/peritoneal cancer (any epithelial histology - mucinous, clear cell, carcinosarcoma, high/low grade serous, endometrioid) who have failed in adequate standard treatments, do not have effective standard treatment or are intolerant to standard of care. Inclusion criteria of participants under arm Module 2 (GSK5733584 +/- Bevacizumab) Ovarian Cancer Part 2B: 1. Participants whose advanced ovarian cancer/fallopian tube/peritoneal cancer has relapsed more than 6 months from the last dose of platinum before enrollment, i.e., platinum sensitive. 2. Participants who have progressed on or are intolerant to at least 1 line of standard prior lines of chemotherapy and are not candidates for second cytoreductive surgery. * Participants willing to use adequate contraception. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: * Is a Woman of non-childbearing potential (WONCBP) OR * Is a Woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective. * A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention * Has an ECOG performance status of 0 to 1. * Participants with normal organ and bone marrow function.
Exclusion criteria
* Has a second malignancy (except disease under study) that has progressed or required active treatment within the past 24 months except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas \[e.g., breast, cervix, bladder\] that have been resected with no evidence of metastatic disease. * Has had any major surgery within 28 days prior to enrolment. * Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant. * Has known sensitivity to study intervention components, Mo-Rez (antibody-drug conjugate, antibody, free cytotoxin GSK5757810A) and combination partner, or its excipients or other allergy that, in the opinion of the investigator, contraindicates participation in the study. * Has any following cardiological examination abnormality: 1. history in prior year of clinically significant or uncontrolled cardiac disease, acute myocardial infarction, NYHA Class III or IV congestive heart failure or clinically significant arrhythmia not controlled by standard of care therapy. 2. Corrected QT Interval (QTcF) \>450 millisecond (msec) or QTcF \>480 msec for participants with bundle branch block * Has untreated brain or CNS metastases or brain/CNS metastases rapidly progressing requiring urgent medical intervention. * Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis. * Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is not considered a form of systemic therapy (e.g., thyroid hormone for autoimmune thyroiditis or insulin is not exclusionary). * Clinically significant bleeding symptoms, significant bleeding tendency, or bleeding tumors within 1 month prior to the first dose of study treatment. * Serious or poorly controlled hypertension, including history of hypertensive crisis, hypertensive encephalopathy; adjustment of antihypertensive medications due to poor blood pressure control within 2 weeks prior to the first dose of study treatment; * Has any active renal condition (e.g., infection, requirement for dialysis, or any other active significant renal condition or dehydrated condition that could affect the participant's safety). Note: renal obstruction successfully managed by stenting is permitted. * Has any serious and/or unstable medical condition (such as clinical symptoms of intestinal obstruction) or psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant's safety, obtainment of informed consent, or compliance to the study procedures. * Participants with known history of Human immunodeficiency virus (HIV).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Percentage of participants with dose limiting toxicities (DLTs) | Approximately 7 months | — |
| Part A: Number of participants with adverse events (AEs), immune-mediated adverse events (imAEs), adverse events of special interest (AESI), serious adverse events (SAEs) by Severity | Up to approximately 22 months | — |
| Part A: Number of participants with adverse events (AEs), immune-mediated adverse events (imAEs), adverse events of special interest (AESI), serious adverse events (SAEs) by Frequency | Up to approximately 22 months | — |
| Part B: Confirmed Objective Response Rate (ORR) | Up to approximately 37 months | ORR is defined as the percentage of participants with a best overall confirmed (BOR) of Partial Response (PR) or better per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Confirmed Objective Response Rate (ORR) | Up to approximately 22 months | ORR is defined as the percentage of participants with a best overall confirmed (BOR) of Partial Response (PR) or better per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) |
| Parts A and B: Duration of response (DoR) | Up to approximately 37 months | DoR is defined as the time from date of first documented evidence of PR or better to the date of disease progression or death due to any cause. |
| Parts A and B: Progression-free survival (PFS) | Up to approximately 37 months | PFS is defined as time from the date of randomization (Part B) / first dose of study intervention (Part A or B if single arm) to the date of disease progression according to investigator assessment or death due to any cause, whichever occurs first. |
| Part B: Overall Survival (OS) | Up to approximately 37 months | OS is defined as the time from randomization (or date of first dose if single arm) to the date of death due to any cause. |
| Part B: Proportion of participants with CA-125 response | Up to approximately 37 months | — |
| Parts A and B: Maximum observed concentration (Cmax) of Mo-Rez | Up to approximately 37 months | — |
| Parts A and B: Time to reach Cmax (tmax) of Mo-Rez | Up to approximately 37 months | — |
| Parts A and B: Trough concentration (Ctrough) of Mo-Rez | Up to approximately 37 months | — |
| Parts A and B: Area under the concentration-time curve (AUC) of Mo-Rez | Up to approximately 37 months | — |
| Parts A and B: Number of participants with Anti-drug antibodies (ADA) | Up to approximately 37 months | — |
| Parts A and B: Number of participants with neutralizing antibody (nAb) | Up to approximately 37 months | — |
| Parts A and B: Titers of ADA to Mo-Rez | Up to approximately 37 months | — |
| Parts A and B: Number of Participants with Clinically Significant Changes in Vital Signs, Laboratory parameters, and Electrocardiogram (ECG) | Up to approximately 37 months | — |
| Part B: Number of participants with adverse events (AEs), immune-mediated adverse events (imAEs), adverse events of special interest (AESI), serious adverse events (SAEs) by Frequency | Up to approximately 37 months | — |
| Part B: Number of participants with adverse events (AEs), immune-mediated adverse events (imAEs), adverse events of special interest (AESI), serious adverse events (SAEs) by Severity | Up to approximately 37 months | — |
| Parts A and B: Change from Baseline in Eastern Cooperative Oncology Group Performance Scale (ECOG PS) score | Baseline and up to approximately 37 months | ECOG PS is used for measuring how the disease impacts a participant's daily living abilities. The grades for the scale range from 0 (fully active) to 5 (dead), with increasing severity. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Denmark, Finland, France, Germany, Greece, Italy, Japan, Mexico, Netherlands, Norway, Panama, Poland, South Korea, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed