Clinical trial NCT06796907: A Study of GSK5733584 in Combination With Anti-cancer Therapies for Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Tumours, Gynecological
Keywords: Solid Tumors
GSK5733584
BEHOLD-2
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2025-01-28
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 GSK5733584 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.


Eligibility criteria: 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 arms (key local diagnostic molecular and/or immunophenotyping testing results/tumor cell phenotype results for confirmed diagnosis should be provided) who have failed in adequate standard treatments, do not have effective standard treatment or are intolerant to standard of care, with no more than 4 lines of prior systemic therapies.
* Requirements for tumor tissue samples: Archival or fresh tumor tissue is required for retrospective central assessment of B7H4 expression by 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 the 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 mm at baseline (for lymph node lesions, the short axis should be ≥ 15 mm).
* Participants have a life expectancy of at least 12 weeks.
* 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:
  * 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

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 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 GSK5757810) 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, or clinically significant arrhythmia not controlled by standard of care therapy.
  2. Corrected QT Interval (QTcF) \>450 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 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 of a medicinal product prior to the first dose of study drug; or need to continue these drugs during the study.
* Use strong inhibitors or inducers of CYP3A4, CYP2D6, P-gp, or breast cancer resistance protein (BCRP) with narrow therapeutic window 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.

Primary outcomes:
measure: Part A: Percentage of participants with dose limiting toxicities (DLTs)
timeFrame: Approximately 7 months
measure: 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
timeFrame: Up to approximately 22 months
measure: 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
timeFrame: Up to approximately 22 months
measure: Part A : Duration of adverse events (AEs), immune-mediated adverse events (imAEs), adverse events of special interest (AESI), serious adverse events (SAEs)
timeFrame: Up to approximately 22 months
measure: Part B: Confirmed Objective Response Rate (ORR)
timeFrame: Up to approximately 37 months
Secondary outcomes:
measure: Part A: Confirmed Objective Response Rate (ORR)
timeFrame: Up to approximately 22 months
measure: Part A and B: Duration of response (DoR)
timeFrame: Up to approximately 37 months
measure: Part A and B: Progression-free survival (PFS)
timeFrame: Up to approximately 37 months
measure: Part B: Overall Survival (OS)
timeFrame: Up to approximately 37 months
measure: Part A and B: Maximum observed concentration (Cmax) of GSK5733584
timeFrame: Up to approximately 37 months
measure: Part A and B: Time to reach Cmax (tmax) of GSK5733584
timeFrame: Up to approximately 37 months
measure: Part A and B: Trough concentration (Ctrough) of GSK5733584
timeFrame: Up to approximately 37 months
measure: Part A and B: Area under the concentration-time curve (AUC) of GSK5733584
timeFrame: Up to approximately 37 months
measure: Part A and B: Maximum observed concentration (Cmax) of GSK5757810
timeFrame: Up to approximately 37 months
measure: Part A and B: Time to reach Cmax (tmax) of GSK5757810
timeFrame: Up to approximately 37 months
measure: Part A and B: Trough concentration (Ctrough) of GSK5757810
timeFrame: Up to approximately 37 months
measure: Part A and B: Area under the concentration-time curve (AUC) of GSK5757810
timeFrame: Up to approximately 37 months
measure: Part A and B: Number of participants with Anti-drug antibodies (ADA)
timeFrame: Up to approximately 37 months
measure: Part A and B: Titers of ADA to GSK5733584
timeFrame: Up to approximately 37 months
measure: Part A and B: Number of Participants with Clinically Significant Changes in Vital Signs, Laboratory parameters, and Echocardiogram (ECG)
timeFrame: Up to approximately 37 months
measure: 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
timeFrame: Up to approximately 37 months
measure: Part B: Duration of adverse events (AEs), immune-mediated adverse events (imAEs), adverse events of special interest (AESI), serious adverse events (SAEs)
timeFrame: Up to approximately 37 months
measure: 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
timeFrame: Up to approximately 37 months
measure: Part A and B: Change from baseline in Eastern Cooperative Oncology Group Performance Scale (ECOG PS) score
timeFrame: Up to approximately 37 months
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
Study officials:
References: