Advanced solid tumors
Conditions
Interventions
Drug: GSK5764227
GSK5764227 will be administered
Drug: Cisplatin
Cisplatin will be administered
Drug: Carboplatin
Carboplatin will be administered
Drug: Atezolizumab
Atezolizumab will be administer
Sponsors
Ishibashi Hideyasu
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Male or female participants at least 18 years of age (>-18 years) -Participants with histologically confirmed advanced/metastatic solid tumors, irrespective of mutational status, as defined per study phase and cohort, as follows: -Participants with advanced/metastatic solid tumors -For monotherapy dose escalation: participants must have progressed on or become intolerant to all available SOC therapies. -For combination dose escalation: participants must have received 3 or fewer prior lines of systemic anticancer therapy in the advanced/metastatic setting -Has at least 1 target lesion per RECIST 1.1, as determined by the investigator. -Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before first dose. -Has adequate organ function. -Where available, participants should provide a formalin fixed and paraffin embedded (FFPE) tumor sample from the most recent biopsy of primary cancer or from a metastatic site for central testing. Tumor tissue is necessary for retrospective detection of B7 homolog 3 protein (B7-H3) expression by Immunohistochemistry (IHC) and other biomarker analysis. -At least one of the following treatment combinations/monotherapy (a, b, c, or d) are not contraindicated. 1. Atezolizumab, durvalumab, or pembrolizumab in combination with cisplatin or carboplatin (for combination 1 only). 2. Atezolizumab, durvalumab, or pembrolizumab as monotherapy (for combination 2 only) 3. Bevacizumab as monotherapy (for combination 3 only) 4. Cetuximab as monotherapy (for combination 4 only) -Additional inclusion criteria for Phase 1b Chinese participants: Chinese participants are considered eligible if they meet all of the following: -Born in mainland China, Hong Kong or Taiwan -Descendant of 2 ethnic Chinese parents and 4 ethnic Chinese grandparents -All participants who do not meet either of the above-mentioned inclusion criteria for Chinese participants will be considered as global (non-Chinese) participants.
Exclusion criteria
Exclusion criteria: -Has ongoing adverse reaction(s) from prior therapy that has(have) not recovered to 450 msec or QTc >480 msec for participants with bundle branch block. - Evidence of current clinically significant arrhythmias or ECG abnormalities (e.g., complete left bundle branch block, third-degree atrioventricular [AV] block, second-degree AV block, PR interval >250 msec). - Risk factors of prolonged QTc or arrhythmia events, such as heart failure, refractory hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death of any direct relative under 40 years old or any concomitant medications that prolong the QT interval. - Left ventricular ejection fraction (LVEF) -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. -History of abdominal or gastrointestinal fistula, tracheoesophageal fistula or any Grade 4 fistula, gastrointestinal perforation, intra-abdominal abscess or active clinical concern for bowel obstruction. -Has any active renal condition (e.g., requirement for dialysis, or any other significant renal condition that could affect the participant's safety). NOTE: renal obstru
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1a: -Number of participants with Adverse Events (AEs) -Number of participants with Dose Limiting Toxicities (DLTs) -Number of participants with AEs and serious adverse events (SAEs) and adverse events of special interest (AESIs) by severity -Number of participants with AEs leading to dose modifications -Number of participants with changes in vital signs, body weight, laboratory tests, electrocardiogram (ECG) and Eastern Cooperative Oncology Group (ECOG) performance status Phase 1b: -Objective Response Rate (ORR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase 1a and Phase 1b: -Maximum concentration (Cmax) of GSK5764227 -Time to reach maximum concentration (Tmax) of GSK5764227 -Area under the curve (AUC) of GSK5764227 -Trough concentration (Ctrough) of GSK5764227 (conjugated antibody, total antibody, small-molecule toxin) Phase 1a: -Objective Response Rate -Disease control rate (DCR) -Duration of Response (DoR) Phase 1b: -Disease control rate (DCR) -Duration of Response (DoR) -Prostate-specific Antigen Decrease From Baseline >=50% (PSA50) response rate Phase 1a and Phase 1b: -Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb) -Titers of ADA against GSK5764227 Phase 1b: -Number of participants with AEs, SAEs and AESI by severity -Number of participants with AEs leading to dose modifications -Number of participants with changes in vital signs, body weight, laboratory tests, ECG, ECHO and ECOG performance status -Progression-Free Survival (PFS) | — |
Countries
Argentina, Canada, France, Hong Kong, Italy, Japan, Panama, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactIshibashi
GlaxoSmithKline K.K.
Outcome results
None listed