A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of GSK5733584 for Injection in Subjects With Advanced Solid Tumors
A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of GSK5733584 for Injection in Subjects With Advanced Solid Tumors
Ishibashi Hideyasu
GlaxoSmithKline K.K.
Akasaka Intercity AIR, 1-8-1 Akasaka, Minato-ku, Tokyo, Japan
+81-120-561-007
jp.gskjrct@gsk.com
Ishibashi Hideyasu
GlaxoSmithKline K.K.
Akasaka Intercity AIR, 1-8-1 Akasaka, Minato-ku, Tokyo, Japan
+81-120-561-007
jp.gskjrct@gsk.com
Recruiting
Sept. 17, 2024
10
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
-Males or females aged 18 years or older (>= 18 years).
-Participants with pathologically confirmed advanced solid tumor (who have failed or are intolerant to standard of care).
-Participants have at least one target lesion as assessed per the RECIST 1.1
-Tumor tissue from a newly obtained biopsy or archival tumor tissue is required for retrospective detection of B7
homolog 4 (B7-H4) expression by Immunohistochemistry (IHC) in central laboratory and other biomarker analysis. Tissue from a newly obtained biopsy is preferred. If a newly obtained biopsy is not feasible, archival tumor tissue obtained from the most recent sample prior to the first dose of study drug is acceptable.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 2 and no deterioration within 2 weeks before the first dose.
- Have a life expectancy of at least 12 weeks.
- Endometrial cancer cohort
1.Histologically documented, advanced (metastatic and/or unresectable) or recurrent endometrial cancer.
2.Must have received or are intolerant to 1 but no more than 3 lines of prior systemic therapy.
Maintenance therapy will be considered part of the preceding line of therapy (i.e., not counted independently).
3.Must have had prior platinum and PD(L)-1 inhibitor (in same regimen or in separate regimens), if considered a candidate for this regimen and the regimen is locally available.
4.All epithelial histologies are permitted including carcinosarcoma.
- Ovarian cancer cohort
1.Histologically documented, advanced (metastatic and/or unresectable) high-grade serous/endometrioid ovarian, primary peritoneal, or fallopian tube cancer.
2.Must have received or are intolerant to 1 but no more than 3 lines of prior systemic therapy.
3.Platinum-resistant disease, defined as progression or relapse within 6 months after the completion of platinum-based therapy.
4.Must have had prior bevacizumab if the participant was considered a candidate for this regimen and the regimen is locally available.
5.Participants with known FR-alpha expressing tumors must have received mirvetuximab soravtasine if the participants was considered a candidate for this regimen and the regimen is locally available.
6.Participants with known BRCA mutated tumors should have received a PARP inhibitor if the participant was considered a candidate for this regimen and the regimen is locally available.
- Have received any of B7-H4-targeted therapies.
- Have received any of cytotoxic chemotherapy drugs, anti-tumor traditional Chinese medicines or other anti-tumor drugs within 28 days prior to the first dose of study drug; or need to continue 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.
- Presence of pleural/abdominal effusion/ascites requiring clinical intervention; presence of pericardial effusion
- Major surgery within 4 weeks prior to the first dose of study treatment.
- Evidence of brain metastasis unless asymptomatic.
- Has inadequate bone marrow reserve or hepatic/renal functions.
- Mean Fridericia-corrected QT interval (QTcF) > 470 millisecond (msec) on resting ECG.
- Evidence of current clinically significant arrhythmias or ECG abnormalities
- Risk factors of prolonged QTc or arrhythmia events,
- Left ventricular ejection fraction (LVEF) < 50%.
- Have severe, uncontrolled or active cardiovascular disorders, serious or poorly controlled hypertension, clinically significant bleeding symptoms or serious arteriovenous thromboembolic events
- Any evidence of current Interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or pneumonitis requiring high-dose systemic glucocorticoids.
- Have received prior therapy with topoisomerase inhibitors or topoisomerase inhibitor Antibody-drug conjugate (ADCs)
- Endometrial cancer: Mesenchymal tumors of the uterus (uterine sarcomas) not permitted.
- Ovarian cancer:
1. Primary platinum refractory disease defined as those who have progressed on or within 12 weeks of last dose of first line platinum therapy not permitted.
2. Non-epithelial carcinoma, clear-cell, mucinous, germ-cell, low-grade serous, or low-grade endometrioid carcinoma not permitted.
18age old over
No limit
Both
solid tumors, endometrial cancer, ovarian cancer
Drug: GSK5733584
GSK5733584 will be administered intravenously.
Part 1: Number of participants with dose limiting toxicity (DLT)
Part 2: Objective Response Rate (ORR)
PK parameter (Cmax, Tmax, AUC), efficacy (ORR, DCR, DoR, PFS, OS), safety (AEs, SAEs), frequency and titers of ADA, etc.
