A Phase I/II study of GSK5733584 in combination with anti-cancer therapies for advanced solid tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited, Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 May 2025 → ongoing

Decision date (initial)

2025-05-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517147-31-00

ClinicalTrials.gov

NCT06796907

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

Part A (Dose Exploration)
To determine the safety and tolerability of GSK5733584 in combination with other anti-cancer treatments, in order to establish the Recommended Phase 2 Dose (s) for each combination treatment.

Part B (Dose Expansion)
To evaluate the anticancer activity of GSK5733584 in combination with other anti-cancer treatments

Secondary objectives 8

1. Part A (Dose Exploration) •To evaluate the anticancer activity of GSK5733584 in combination with other anti-cancer treatments.
2. Part A (Dose Exploration) •To evaluate the PK profile of GSK5733584 administered in combination with other anti-cancer treatments.
3. Part A (Dose Exploration) •To evaluate the immunogenicity of GSK5733584 administered intravenously in in combination with other anti-cancer treatments.
4. Part A (Dose Exploration) •To further determine the safety and tolerability of GSK5733584 in combination with other anticancer treatments .
5. Part B (Dose Expansion) •To further evaluate the anticancer activity of GSK5733584 in combination with other anti-cancer treatments
6. Part B (Dose Expansion) •To evaluate the PK profile of GSK5733584 administered alone or in combination with other anti-cancer treatments.
7. Part B (Dose Expansion) •To evaluate the immunogenicity of GSK5733584 administered alone or with other anti-cancer treatments.
8. Part B (Dose Expansion) •To further characterize the safety and tolerability of GSK5733584 in combination with other anticancer treatments.

Conditions and MedDRA coding

Tumours, Gynecological

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Federal Agency For Medicines And Health Products, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

IPD plan description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months. IPD Sharing Time Frame:Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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
2. Participants with pathologically confirmed advanced solid tumor (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: a. Adjuvant ± neoadjuvant considered one line of therapy b. Maintenance therapy will be considered as part of the preceding line of therapy (i.e., not counted independently) c. 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 (eg. hypersensitivity reaction) this is considered part of the same line (i.e. not counted independently).
3. 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.
4. 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.
5. Participants have a life expectancy of at least 12 weeks per investigator assessment based on disease burden and extent of supportive care needed.
6. Is willing to use adequate contraception. Contraceptive use by men or women should be consistent with Protocol Section 10.4
7. Has an ECOG performance status of 0 to 1
8. Participants with normal organ and bone marrow function as defined in Protocol Table 15

Exclusion criteria 18

1. 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
2. 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)
3. Clinically significant bleeding symptoms, significant bleeding tendency, or bleeding tumors within 1 month prior to the first dose of study treatment
4. 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
5. 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). Note: renal obstruction successfully managed by stenting is permitted
6. Is pregnant or breastfeeding
7. Has an ALT value >2.5x ULN and for participants with documented liver metastases/tumor infiltration has an ALT value >5x ULN.
8. Has a total bilirubin value >1.5x ULN. NOTE: Participants with Gilbert’s syndrome can be included with a total bilirubin value <3x ULN, provided direct bilirubin is <1x ULN and participant otherwise meets entry criteria.
9. Has received prior therapy with topoisomerase-1 inhibitors or ADC with topoisomerase-1 inhibitor warhead, or B7H4 targeted therapy
10. 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
11. Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant
12. 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.
13. Has any following cardiological examination abnormality : a. history in prior year of clinically significant or uncontrolled cardiac disease, acute myocardial infarction, New York Heart Association Class III or IV congestive heart failure [1994], or clinically significant arrhythmia not controlled by standard of care therapy. b. QTcF >450 msec or QTcF >480 msec for participants with bundle branch block
14. Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis
15. Use of strong or moderate inhibitors or inducers of CYP3A4, CYP2D6, and inhibitors or inducers of P-gp, and BCRP within 14 days prior to the first dose of study drug; or in need of continuing treatment with these drugs during the study
16. Has serious infections within 4 weeks prior to the first dose, including but not limited to infectious complications, bacteremia, severe pneumonia treated with intravenous antibiotics for ≥2 weeks; Participants who are receiving or have received prophylactic antibiotics (e.g., prophylaxis against urinary infections) are allowed
17. Has chronic inflammatory bowel disease and/or bowel obstruction
18. Has any serious and/or unstable medical condition (such as clinical symptoms of intestinal obstruction) or psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant’s safety, obtainment of informed consent, or compliance to the study procedures.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part A (Dose Exploration) •Percentage of participants with dose limiting toxicities (DLTs) per dose level •Frequency and severity of AEs, imAEs (dostarlimab Modules), AESIs and SAEs per dose level.
2. Part B Dose Expansion •Clinical activity measured as confirmed ORR assessed by investigator according to RECIST 1.1

Secondary endpoints 8

1. Part A (Dose Exploration) •Clinical activity measured as confirmed ORR, DoR, and PFS by dose level assessed by investigator according to RECIST v1.1.
2. Part A (Dose Exploration) PK parameters (e.g., Cmax, tmax, Ctrough, AUC) for GSK5733584 (conjugated antibody and payload) as data permit.
3. Part A (Dose Exploration) •Incidence of ADA, nAb and ADA titers.
4. Part A (Dose Exploration) •Changes in vital signs, laboratory measures, ECGs, and Eastern Cooperative Oncology Group Performance Status (ECOG PS) score.
5. Part B Dose Expansion Clinical activity measured as DoR, PFS assessed by investigator according to RECIST 1.1 and OS
6. Part B Dose Expansion PK parameters (e.g., Cmax, tmax, Ctrough, AUC) for GSK5733584 (conjugated antibody and payload), as data permit
7. Part B Dose Expansion •Incidence of ADA, nAb and ADA titers.
8. Part B Dose Expansion •Frequency and severity of AEs, imAEs (dostarlimab Modules), AESIs and SAEs per dose level •Changes in vital signs, laboratory measures, ECGs, and ECOG PS score.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

79 New Oxford Street

City

London

Postcode

WC1A 1DG

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 22

Sponsor responsibilities

Article 77 compliance

Glaxosmithkline Research & Development Limited

Contact point sponsor

Glaxosmithkline Research & Development Limited

Article 77 implementation

Glaxosmithkline Research & Development Limited

Locations

12 EU/EEA countries · 48 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 150 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications