Informations générales (source: ClinicalTrials.gov)
A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Clinical Activity of GSK5764227 as Monotherapy and in Combination in Participants With Advanced Solid Tumors
Interventional
Phase 1
GlaxoSmithKline (Voir sur ClinicalTrials)
septembre 2024
mai 2027
02 décembre 2025
The goal of this study is to assess the safety, tolerability, clinical activity and
pharmacokinetics of GSK5764227. The study will also see how the levels of GSK5764227 will
change over time at different dose amounts when administered alone and in combination
with other medicines like carboplatin, cisplatin, atezolizumab, pembrolizumab,
durvalumab, bevacizumab, cetuximab.
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 | 16/04/2026 08:55:05 | Contacter | ||
Critères
Tous
- 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:
o Phase 1a:
- 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 a life expectancy >12 weeks.
- Has adequate organ function. Screening specimens must be collected at least 3-5 days
prior to pre-dose specimens, and pre-dose specimens must be collected within 24
hours prior to first dose.
- 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 (archival tumor tissue or a fresh
biopsy) for all except ES-SCLC participants. Exemptions can be granted by the
medical monitor for participants with bladder cancer and mCRPC. 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)
- Has received no more than 4 cycles of cisplatin or carboplatin in combination with
pembrolizumab, atezolizumab, or durvalumab as most recent treatment regimen, with
objective response (per RECIST 1.1) of SD or better and no PD, and otherwise
qualifies for continued treatment with atezolizumab, durvalumab, or pembrolizumab
per local practice guidelines (combination 2 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:
- Has ongoing adverse reaction(s) from prior therapy that has(have) not recovered to
≤Grade 1 or to the baseline status preceding prior therapy.
- Prior treatment with orlotamab, enoblituzumab, I-Dxd, or other B7-H3 targeted
agents.
- Evidence of brain metastasis (unless meeting the following criteria at the same
time: asymptomatic; medically stable for at least 4 weeks prior to initial dosing;
no steroid treatment required for at least 2 weeks prior to initial dosing; and no
midline shift due to herniation); or untreated progression due to brain metastasis
during or after the last treatment prior to screening; or evidence of
meningeal/brainstem metastasis; or evidence of spinal cord compression (detected by
radiographic examination, symptomatic or not).
- Any of the following cardiac examination abnormality:
- Has QT interval, corrected for heart rate (QTc) >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) <50%.
- Has severe, uncontrolled or active CV 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 non-infectious pneumonitis requiring
high-dose glucocorticoids.
- Has donated blood or blood products in excess of 500 mL (approximately 1 pint)
within one month prior to first dose of study treatment.
- Has a history of autoimmune disease that has required systemic treatments in the 2
years prior to screening. Participants with prior history of autoimmune disease must
be discussed with the medical monitor. Replacement therapy is not considered a form
of systemic therapy (e.g., thyroid hormone for autoimmune thyroiditis or insulin is
not exclusionary).
- Has any history of prior allogenic or autologous bone marrow transplant or other
solid organ transplant.
- Has received immunosuppressive agents within 30 days prior to first dose of study
treatment (or requires long-term (30 days or longer) glucocorticoid therapy).
Low-dose corticosteroids (prednisone ≤10 mg/day or equivalent) may be administered.
Use of inhaled or topical steroids and prophylactic corticosteroids for procedures
are permitted.
- Participants in dehydrated condition.
- Participant with history of nephrotic syndrome or Grade 3 proteinuria. Participants
discovered to have ≥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, or intra-abdominal abscess.
- History of bowel involvement on CT scan or clinical symptoms of 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
obstruction successfully managed by stenting is permitted.
Additional exclusion criteria for participants receiving combination therapy
- Has received prior systemic anticancer therapy within 28 days of first dose of study
treatment (combinations 1, 3 and 4 only).
- Has experienced any of the following with prior immunotherapy: any immune-mediated
adverse event [imAE] ≥ Grade 3, immune-mediated severe neurologic events of
any-grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré
Syndrome, or transverse myelitis), exfoliative dermatitis of any grade
(Stevens-Johnson syndrome [SJS], Toxic epidermal necrolysis [TEN], or Drug reaction
with eosinophilia and systemic symptoms [DRESS] syndrome), or myocarditis of any
grade. Clinically significant laboratory abnormalities, as judged by investigator,
are not exclusionary.