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📋 Trial Overview & PurposeThis study addresses the challenge of advanced solid tumors—cancers that have spread and often become resistant to existing treatments. The core purpose is to evaluate the safety, tolerability, pharmacokinetics (how the body handles the drug), and preliminary effectiveness of GSK5733584 when used alongside other established cancer medicines. The drug being studied, GSK5733584, is an Antibody-Drug Conjugate (ADC). ADCs are highly targeted therapies that link a potent chemotherapy agent to an antibody. This antibody is designed to seek out and attach to specific markers on cancer cells (in this case, the study requires testing for B7H4 expression), delivering the chemotherapy directly to the tumor while minimizing damage to healthy tissues. 🧪 Study Design & MethodologyThe trial is structured as a combined Phase 1 and Phase 2 study, enrolling an estimated 392 participants:
The study is interventional and non-masked (meaning both the patient and the research team know which treatment is being administered). ✅ Eligibility & Participation RequirementsThis trial is currently RECRUITING participants who meet specific criteria:
📢 Notice: Participants with a history of certain conditions, such as recent cardiac events, uncontrolled arrhythmias, or current interstitial lung disease (ILD) or pneumonitis, are excluded. 📊 Measured Outcomes/EndpointsThe study aims to measure both safety and efficacy over a period of up to 37 months:
For complete details on the study plan, including specific intervention arms and locations, please check the Trial Radar Card View. Always consult with your healthcare provider before considering participation in any clinical trial. One study matched filter criteria. | |||||||||||||||||
GlaxoSmithKlineA Study of GSK5733584 in Combination With Anti-cancer Therapies for Advanced Solid Tumors (BEHOLD-2) Phase 1, Phase 2 392
A Phase I/II Randomized Multi-Cohort Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of GSK5733584 in Combination With Anti-Cancer Agents in Participants With Advanced Solid Tumors
- BEHOLD-2
- 223559
- 2024-517147-31-00 (Registry Identifier) (CTIS)
Phase 2
GSK5733584
BEHOLD-2
| Participant Group/Arm | Intervention/Treatment |
|---|---|
ExperimentalModule 1 (GSK5733584 +/- Dostarlimab) Endometrial Cancer | GSK5733584 GSK5733584 will be administered intravenously (IV). Dostarlimab Dostarlimab will be administered IV. |
ExperimentalModule 2 (GSK5733584 +/- Bevacizumab) Ovarian Cancer | GSK5733584 GSK5733584 will be administered intravenously (IV). Bevacizumab Bevacizumab will be administered IV. |
ExperimentalModule 3 (GSK5733584 + Anticancer therapy 3 +/- Dostarlimab or Bevacizumab) | GSK5733584 GSK5733584 will be administered intravenously (IV). Dostarlimab Dostarlimab will be administered IV. Bevacizumab Bevacizumab will be administered IV. Anticancer therapy 3 Anticancer therapy 3 will be administered IV. |
ExperimentalModule 4 (GSK5733584 + Anticancer therapy 4 +/- Dostarlimab or Bevacizumab) | GSK5733584 GSK5733584 will be administered intravenously (IV). Dostarlimab Dostarlimab will be administered IV. Bevacizumab Bevacizumab will be administered IV. Anticancer therapy 4 Anticancer therapy 4 will be administered IV. |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
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) | 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) | Up to approximately 37 months |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Part A: Confirmed Objective Response Rate (ORR) | ORR is defined as the percentage of participants with a best overall confirmed (BOR) of PR or better per RECIST 1.1. | Up to approximately 22 months |
Parts A and B: Duration of response (DoR) | 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. | Up to approximately 37 months |
Parts A and B: Progression-free survival (PFS) | 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. | Up to approximately 37 months |
Part B: Overall Survival (OS) | 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. | Up to approximately 37 months |
Parts A and B: Maximum observed concentration (Cmax) of GSK5733584 | Up to approximately 37 months | |
Parts A and B: Time to reach Cmax (tmax) of GSK5733584 | Up to approximately 37 months | |
Parts A and B: Trough concentration (Ctrough) of GSK5733584 | Up to approximately 37 months | |
Parts A and B: Area under the concentration-time curve (AUC) of GSK5733584 | 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 GSK5733584 | 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 | ECOG PS is used for measuring how the disease impacts a participants daily living abilities. The grades for the scale range from 0 (fully active) to 5 (dead), with increasing severity. | Baseline and up to approximately 37 months |
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 arms (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:
- Adjuvant +/- neoadjuvant considered one line of therapy
- Maintenance therapy will be considered as part of the preceding line of therapy (i.e., not counted independently)
- 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 (GSK5733584 +/- Dostarlimab) Endometrial Cancer Part A:
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 (GSK5733584 +/- Dostarlimab) Endometrial Cancer Part B:
- Diagnosis of endometrial cancer with confirmed mismatch repair proficient (MMRp) or microsatellites stable (MSS) tumor status by local test.
- 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).
- Participants naïve to anti-programmed death protein 1 and/or programmed death ligand 1 (PD\[L\]-1) anti-cancer therapy.
Inclusion criteria of participants under arm Module 2 (GSK5733584 +/- Bevacizumab) Ovarian Cancer Part A:
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 B:
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.
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.
Male participants:
- Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 6 months after the last dose of study intervention for Arms 1 to 3 and 11 Months after the last dose of study intervention for Arm 4:
- Refrain from donating sperm.
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
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 any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
Has known sensitivity to study intervention components, GSK5733584 (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:
- history in prior year of clinically significant or uncontrolled cardiac disease, acute myocardial infarction, or clinically significant arrhythmia not controlled by standard of care therapy.
- Corrected QT Interval (QTcF) >450 millisecond (msec) or QTcF >480 msec for participants with bundle branch block
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; systolic blood pressure ≥ 160 millimeter of mercury (mmHg) or diastolic blood pressure ≥ 100 mmHg during screening period.
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).
Participants with known history of Human immunodeficiency virus (HIV).
Has an Alanine transaminase (ALT) value >2.5x Upper Limit of Normal (ULN) and for participants with documented liver metastases/tumor infiltration has an ALT value >5x ULN.
Has a total bilirubin value >1.5x ULN.
Has received treatment with any cytotoxic chemotherapy drugs or other anti-tumor drugs (including endocrine therapy, molecular targeted therapy, immunotherapy, biotherapy, and investigational drug) within 30 days or 5 half-lives, whichever is shorter of a medicinal product prior to the first dose of study drug; or need to continue these drugs during the study.
Use of strong or moderate inhibitors or inducers of CYP3A4, CYP2D6 and inhibitors or inducers of P-gp, and breast cancer resistance protein (BCRP) within 14 days prior to the first dose of study drug; or in need of continuing treatment with these drugs during the study.
Have received locoregional radiation therapy within 2 weeks prior to the first dose of study drug; more than 30% of bone marrow irradiation or wide-field radiation therapy within 4 weeks prior to the first dose of study treatment.
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