Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 1/Phase 2
GlaxoSmithKline (Voir sur ClinicalTrials)
mars 2025
avril 2028
02 décembre 2025
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Yohann LORIOT | 30/04/2026 09:15:06 | Contacter | ||
Critères
Tous
- 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:
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 (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:
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).
3. 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:
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.
- 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
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 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, 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
- 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.