BridgeMD
A Phase 1b/2 study of GSK5764227 in combination with Standard of Care (SoC) or other agents in participants with advanced solid tumors
EU CTIS ID: 2025-522274-37-00
What this study is testing
To determine the MTD/MAD and evaluate the safety and tolerability of GSK5764227 when administered in combination with SoC in participants with advanced solid tumors.
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Is at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the ICF.
- Cohort B: PSA ≥ 1 ng/mL during the screening period.
- Cohort B: Serum testosterone level ≤ 50 ng/dL or 1.7 nmol/L during the screening period. Patients must have undergone bilateral orchiectomy or be on continuous androgen-deprivation therapy with a GnRH agonist or antagonist; this therapy must have been initiated at least 4 weeks prior to randomization and treatment must be continued throughout the study.
- Cohort B: Progression on or intolerance to SoC lines of therapy in the mCRPC stage [including, but not limited to, docetaxel, ARPI/ novel hormone therapies (such as enzalutamide, apalutamide, darolutamide), and radio-ligand therapy, etc.]. Participants who have experienced disease progression while receiving NHA in mHSPC are allowed. • If the participant is intolerant to NHA, refuses it, or cannot receive it for other reasons, they may be eligible if they have experienced disease progression after receiving at least one systemic chemotherapy regimen. • First-generation antiandrogen therapy (i.e., bicalutamide, flutamide, nilutamide) are not considered a novel hormonal agent or a chemotherapy regimen. Participants who have taken first-generation antiandrogen therapeutic drugs must have a washout period of at least 28 days before enrolment. • Progressive disease is defined as (at least one of the following): • PSA progression: PSA > 1 ng/mL and 2 consecutive increases in PSA at least 1 week apart (compared to current treatment baseline or the nadir during the treatment period) per PCWG3 criteria; and/or • Progression of soft tissue lesions according to RECIST 1.1 criteria; and/or • Bone lesion progression according to PCWG3 criteria.
- Cohort B: Has metastatic prostate cancer that includes: ≥1 measurable soft tissue per RECIST 1.1 (not including regional Lymph Nodes) and/or ≥1 metastatic bone lesion per PCWG3 criteria (not a superscan) on bone scintigraphy, at screening.
- Cohort B: Where available, participants should provide an archival tumor sample from the most recent biopsy (FFPE block preferred) of primary cancer or from a metastatic site at screening (preferably taken after the completion of the participant’s last line of therapy prior to the first dose of study drug).
You likely can't join if
- Has a 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 disease.
- Cohort A: Serious non-healing wound, non-healing ulcer or non-healing bone fracture. Note: If the participant has had surgery, the wound must be fully healed prior to first dosing.
- Cohort A: Confirmed uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 150 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg) or uncontrolled or symptomatic arrhythmia.
- Cohort A: Has a history of nephrotic syndrome or Grade 3 proteinuria. Participants discovered to have ≥2 proteinuria on at screening should undergo a 24 hour urine collection and must demonstrate ≤1 g of protein in 24 hours to be eligible.
- Cohort A: Known coagulopathy that increases risk of bleeding, bleeding diatheses. Any other hemorrhage/bleeding event CTCAE grade ≥ 3 within 4 weeks prior to first dosing.
- Cohort A: Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to first dosing.
See the full eligibility criteria
Who can join
- Is at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the ICF.
- Cohort B: PSA ≥ 1 ng/mL during the screening period.
- Cohort B: Serum testosterone level ≤ 50 ng/dL or 1.7 nmol/L during the screening period. Patients must have undergone bilateral orchiectomy or be on continuous androgen-deprivation therapy with a GnRH agonist or antagonist; this therapy must have been initiated at least 4 weeks prior to randomization and treatment must be continued throughout the study.
- Cohort B: Progression on or intolerance to SoC lines of therapy in the mCRPC stage [including, but not limited to, docetaxel, ARPI/ novel hormone therapies (such as enzalutamide, apalutamide, darolutamide), and radio-ligand therapy, etc.]. Participants who have experienced disease progression while receiving NHA in mHSPC are allowed. • If the participant is intolerant to NHA, refuses it, or cannot receive it for other reasons, they may be eligible if they have experienced disease progression after receiving at least one systemic chemotherapy regimen. • First-generation antiandrogen therapy (i.e., bicalutamide, flutamide, nilutamide) are not considered a novel hormonal agent or a chemotherapy regimen. Participants who have taken first-generation antiandrogen therapeutic drugs must have a washout period of at least 28 days before enrolment. • Progressive disease is defined as (at least one of the following): • PSA progression: PSA > 1 ng/mL and 2 consecutive increases in PSA at least 1 week apart (compared to current treatment baseline or the nadir during the treatment period) per PCWG3 criteria; and/or • Progression of soft tissue lesions according to RECIST 1.1 criteria; and/or • Bone lesion progression according to PCWG3 criteria.
- Cohort B: Has metastatic prostate cancer that includes: ≥1 measurable soft tissue per RECIST 1.1 (not including regional Lymph Nodes) and/or ≥1 metastatic bone lesion per PCWG3 criteria (not a superscan) on bone scintigraphy, at screening.
- Cohort B: Where available, participants should provide an archival tumor sample from the most recent biopsy (FFPE block preferred) of primary cancer or from a metastatic site at screening (preferably taken after the completion of the participant’s last line of therapy prior to the first dose of study drug).
- Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before first dose.
- Has adequate organ function.
- Cohort A: Has histologically confirmed unresectable adenocarcinoma or unresectable metastatic adenocarcinoma of the colon or rectum (histology defined by WHO classification).
- Cohort A: Must have received at least 1 and no more than 2 lines of systemic treatment for advanced CRC, with documented progression on most recent prior line of therapy Prior lines of therapy must have included treatment with either a fluoropyrimidine, oxaliplatin and/or irinotecan, an anti-VEGF monoclonal antibody and/or an anti-EGFR monoclonal antibody, if the approved biologic therapy(ies) is available. In addition, per local practice guidelines, qualifies for treatment with Bevacizumab and/or 5-FU/LV. • Participants with dMMR/MSI-H status may be eligible if they have received prior ICI therapy (if an approved ICI(s) is available) and also meet all other criteria related to prior therapies as listed above. • Participants with known targetable genomic aberrations may be eligible if they meet all other criteria related to prior therapies as listed above and have received the following (if the approved biomarker-directed therapy/-ies is/are available): • KRAS G12C mutation, e.g., adagrasib or sotorasib • BRAF V600E mutation, e.g., encorafenib • HER2 amplification, e.g., trastuzumab with another agent (NOTE: participants who received treatment with T-DX1 are excluded) • Participants who received neoadjuvant or adjuvant chemotherapy and experienced disease progression during treatment or within 6 months of the EOT may count this therapy as a line of treatment.
- Cohort A: Has at least 1 target lesion per RECIST 1.1, as determined by the investigator. Measurable lesions that have been previously irradiated and have been shown to be progressing following irradiation may be considered as target lesions. NOTE: It is preferable not to have a pathological lymph node as a singular target lesion.
- Cohort A: Participants must provide tissue from a biopsy taken from primary cancer or metastatic site. Fresh biopsy is preferred. If a fresh biopsy is not feasible, archival FFPE blocks (preferred) or slides from the most recent biopsy are acceptable (preferably taken after the completion of the participant’s last line of therapy prior to the first dose of study drug). Tissue is required for retrospective B7-H3 expression analysis by IHC and other biomarker evaluations. Exceptions may be granted by the medical monitor if tissue is unavailable.
- Cohort B: Histologically or cytologically confirmed adenocarcinoma of the prostate.
- Cohort B: Metastatic (stage IVB) disease, excluding participants with metastatic disease restricted to pelvic lymph nodes or rectum.
What rules you out
- Has a 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 disease.
- Cohort A: Serious non-healing wound, non-healing ulcer or non-healing bone fracture. Note: If the participant has had surgery, the wound must be fully healed prior to first dosing.
- Cohort A: Confirmed uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 150 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg) or uncontrolled or symptomatic arrhythmia.
- Cohort A: Has a history of nephrotic syndrome or Grade 3 proteinuria. Participants discovered to have ≥2 proteinuria on at screening should undergo a 24 hour urine collection and must demonstrate ≤1 g of protein in 24 hours to be eligible.
- Cohort A: Known coagulopathy that increases risk of bleeding, bleeding diatheses. Any other hemorrhage/bleeding event CTCAE grade ≥ 3 within 4 weeks prior to first dosing.
- Cohort A: Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to first dosing.
- Cohort A: Deep venous thromboembolic event within 3 months prior to first dosing or any previous NCI CTCAE grade 4 venous thromboembolism.
- Has known complete DPD deficiency (Cohort A2 only).
- Principal Exclusion Criteria Cohort A: Has received treatment with any of the following within the specified timeframe prior to the first dose of study drug: • Strong or moderate inhibitors of CYP3A4, CYP2D6, or inhibitors of P-gp or BCRP, within 7 days prior to the first dose of study drug. • Strong or moderate inducers of CYP3A4 or inducers of P-gp, within 14 days prior to the first dose of study drug.
- Cohort B: Has serious arteriovenous thromboembolic events (such as deep vein thrombosis, pulmonary embolism, etc.) within 3 months prior to the first dose (except for implantable venous port, catheter-related thrombosis, or superficial vein thrombosis, which are not considered "serious" (thromboembolism).
- Cohort B: Has 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; or recurrent systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg during Screening period
- Has had any major surgery within 28 days prior to first dose.
- Cohort B: Has a history of nephrotic syndrome or Grade 3 proteinuria. Participants discovered to have ≥2 proteinuria on dipstick at screening should undergo a 24 hour urine collection and must demonstrate <2 g of protein in 24 hours to be eligible.
- Cohort B: Has received treatment with any of the following within the specified timeframe prior to the first dose of study drug: • Strong or moderate inhibitors of CYP3A4, CYP2D6, or strong inhibitors of CYP2C8, or inhibitors of P-gp or BCRP, within 7 days prior to the first dose of study drug. • Strong or moderate inducers of CYP3A4 (except enzalutamide) or inducers of P-gp, within 14 days prior to the first dose of study drug. • CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, within 7 days prior to the first dose of enzalutamide.
- Has clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose.
- Has serious infection within 4 weeks prior to the first dose, including but not limited to infectious complications, bacteremia, severe pneumonia treated with IV antibiotics for ≥2 weeks; active infections with therapeutic IV antibiotics within 2 weeks prior to the first dose. Participants who are receiving or have received prophylactic antibiotics (e.g., prophylaxis against urinary infections) are allowed.
- Has untreated brain or CNS metastases or brain/CNS metastases that have progressed [e.g., evidence of new or enlarging brain metastasis or new neurologic symptoms attributable to brain/CNS metastases]. Participants with previously treated and clinically stable brain/CNS metastases and who have completed all corticosteroid therapy for at least 4 weeks prior to dosing are not excluded from participation.
- Any evidence of current ILD or pneumonitis OR a prior history of ILD requiring high-dose glucocorticoids or non infectious pneumonitis requiring high-dose glucocorticoids.
- Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening. Participants with prior history of autoimmune disease must be discussed with the medical monitor. Replacement therapy is not considered a form of systemic therapy (e.g., thyroid hormone for autoimmune thyroiditis or insulin is not exclusionary).
- Has received any prior therapy with an ADC with a TOPO1-inhibitor payload.
- Cohort A: History of abdominal or gastrointestinal fistula, tracheoesophageal fistula or any Grade 4 fistula, gastrointestinal perforation, or intra‑abdominal abscess or active clinical concern for bowel obstruction.
The study team makes the final eligibility decision.
Where it's taking place
- Korea, Republic of
- Canada
- United Kingdom
- United States
- Australia
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Korea, Republic of; Canada; United Kingdom; United States; Australia. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.