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 Identifier:
223559
CT.gov Identifier:
NCT06796907
EudraCT Identifier:
2024-517147-31
EU Trial (CTIS) Number:
2024-517147-31-00
Study Contact Information:
N/A
Recruiting

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Study 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.

To evaluate HS-20089 for the treatment of gynecologic cancers

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Other
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Module 1 (GSK5733584 +/- Dostarlimab) Endometrial Cancer
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  • Drug: Intervention/Treatment
  • Drug: Drug: Dostarlimab
  • Drug: Experimental: Module 2 (GSK5733584 +/- Bevacizumab) Ovarian Cancer
  • Drug: Drug: GSK5733584
  • Drug: Drug: Bevacizumab
  • Drug: Experimental: Module 3 (GSK5733584 + Anticancer therapy 3 +/- Dostarlimab or Bevacizumab)
  • Drug: Drug: Anticancer therapy 3
  • Drug: Experimental: Module 4 (GSK5733584 + Anticancer therapy 4 +/- Dostarlimab or Bevacizumab)
  • Drug: Drug: Anticancer therapy 4
  • Drug: DOSTARLIMAB
  • Drug: CTIS:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion 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) 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
    Exclusion criteria
    • 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:
    • 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.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Ramon Yarza
    Status
    Recruiting
    Condition(s) Treated at Site
    Other
    Location
    START Barcelona
    Barcelona, Spain, 08023
    Investigator
    Tatiana Hernandez Guerrero
    Status
    Will Be Recruiting
    Condition(s) Treated at Site
    Other