A Study of GSK5764227 in Participants With Advanced Solid Tumors (EMBOLD)

Официальное название

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

Обзор

The goal of this study is to assess the safety, tolerability, clinical activity and pharmacokinetics of Risvutatug rezetecan (Ris-Rez), also known as GSK5764227. The study will also see how the levels of Ris-Rez 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, tarlatamab, dostarlimab

Вмешательства

• Биопрепарат Ris-Rez
  Ris-Rez will be administered
• Препарат Cisplatin
  Cisplatin will be administered
• Препарат Carboplatin
  Carboplatin will be administered
• Биопрепарат Atezolizumab
  Atezolizumab will be administered
• Биопрепарат Pembrolizumab
  Pembrolizumab will be administered
• Биопрепарат Durvalumab
  Durvalumab will be administered
• Биопрепарат Cetuximab
  Cetuximab will be administered
• Биопрепарат Bevacizumab
  Bevacizumab will be administered
• Биопрепарат Tarlatamab
  Tarlatamab will be administered
• Биопрепарат Dostarlimab
  Dostarlimab will be administered

Первичные конечные точки

• Phase 1a: Number of participants with Adverse Events (AEs) [Срок оценки: Up to approximately 28 months]
• Phase 1a: Number of participants with Dose Limiting Toxicities (DLTs) [Срок оценки: Up to 21 days]
• Phase 1a: Number of participants with AEs, serious adverse events (SAEs) and adverse events of special interest (AESIs) by severity [Срок оценки: Up to approximately 30 months]
• Phase 1a: Number of participants with AEs leading to dose modifications [Срок оценки: Up to approximately 28 months]
• Phase 1a: Number of participants with changes in vital signs, body weight, laboratory tests, electrocardiogram (ECG) and Eastern Cooperative Oncology Group (ECOG) performance status [Срок оценки: Up to approximately 28 months]
• Phase 1b: Confirmed Objective Response Rate (cORR) [Срок оценки: Up to approximately 27 months]

Вторичные конечные точки (12)

• Phase 1a and Phase 1b: Maximum concentration (Cmax) of Ris-Rez [Срок оценки: Up to approximately 28 months]
• Phase 1a and Phase 1b: Time to reach maximum concentration (Tmax) of Ris-Rez [Срок оценки: Up to approximately 28 months]
• Phase 1a and Phase 1b: Area under the curve (AUC) of Ris-Rez [Срок оценки: Up to approximately 28 months]
• Phase 1a and Phase 1b: Trough concentration (Ctrough) of Ris-Rez (conjugated antibody) [Срок оценки: Up to approximately 28 months]
• Phase 1a and Phase 1b: Trough concentration (Ctrough) of Ris-Rez (total antibody) [Срок оценки: Up to approximately 28 months]
• Phase 1a and Phase 1b: Trough concentration (Ctrough) of GSK5757810 (small-molecule toxin) [Срок оценки: Up to approximately 28 months]
• Phase 1a: Confirmed Objective Response Rate (cORR) [Срок оценки: Up to approximately 33 months]
• Phase 1a: Disease control rate at 12 weeks (DCR12) [Срок оценки: At 12 weeks]
• Phase 1b: Disease control rate at 12 weeks (DCR12) [Срок оценки: At 12 weeks]
• Phase 1a: Duration of Response (DoR) [Срок оценки: Up to approximately 33 months]
• Phase 1b: Duration of Response (DoR) [Срок оценки: Up to approximately 33 months]
• Phase 1b: Proportion of Participants with Tumour antigen Decrease From Baseline >=50% response rate [Срок оценки: Up to approximately 33 months]

Критерии участия

Критерии включения

• Male or female participants at least 18 years of age (≥18 years)
• Participants with histologically confirmed advanced/metastatic solid tumors, as defined per study phase and cohort, as follows:

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 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.

Критерии исключения

• 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.
• Primary brain tumor or 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 4 weeks prior to initial dosing; and no midline shift due to herniation); or untreated progression due to brain metastasis or primary brain tumor during or after the last treatment prior to screening; or evidence of meningeal/brainstem involvement; 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
• Participants with evidence of current ILD/non-infectious pneumonitis OR a prior history of ILD/non-infectious pneumonitis requiring high-dose glucocorticoids OR suspected ILD/non-infectious pneumonitis that cannot be ruled out by imaging.
• 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 prior anticancer therapy within 28 days of the first dose of study intervention or having to continue these medications during the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 15 центров

• GSK Investigational Site — Stanford
• GSK Investigational Site — Denver
• GSK Investigational Site — New Haven
• GSK Investigational Site — Fort Wayne
• GSK Investigational Site — Boston
• GSK Investigational Site — Detroit
• GSK Investigational Site — New Brunswick
• GSK Investigational Site — Myrtle Beach
• … и ещё 7 центров

Испания · 9 центров

• GSK Investigational Site — Badajoz
• GSK Investigational Site — Barcelona
• GSK Investigational Site — Barcelona
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid
• GSK Investigational Site — Málaga
• GSK Investigational Site — Valencia
• … и ещё 1 центр

Тайвань · 6 центров

• GSK Investigational Site — Changhua
• GSK Investigational Site — Kaohsiung City
• GSK Investigational Site — Taichung
• GSK Investigational Site — Tainan
• GSK Investigational Site — Taipei
• GSK Investigational Site — Taipei

Великобритания · 6 центров

• GSK Investigational Site — Edinburgh
• GSK Investigational Site — Glasgow
• GSK Investigational Site — London
• GSK Investigational Site — London
• GSK Investigational Site — Manchester
• GSK Investigational Site — Newcastle upon Tyne

Канада · 5 центров

• GSK Investigational Site — Hamilton
• GSK Investigational Site — Ottawa
• GSK Investigational Site — Toronto
• GSK Investigational Site — Montreal
• GSK Investigational Site — Sherbrooke

Япония · 5 центров

• GSK Investigational Site — Aichi
• GSK Investigational Site — Chiba
• GSK Investigational Site — Shizuoka
• GSK Investigational Site — Tokyo
• GSK Investigational Site — Tokyo

Израиль · 4 центра

• GSK Investigational Site — Jerusalem
• GSK Investigational Site — Jerusalem
• GSK Investigational Site — Ramat Gan
• GSK Investigational Site — Tel Aviv

Италия · 4 центра

• GSK Investigational Site — Milan
• GSK Investigational Site — Naples
• GSK Investigational Site — Roma
• GSK Investigational Site — Verona

South Korea · 4 центра

• GSK Investigational Site — Gyeonggi-do
• GSK Investigational Site — Seoul
• GSK Investigational Site — Seoul
• GSK Investigational Site — Seoul

Франция · 3 центра

• GSK Investigational Site — Bordeaux
• GSK Investigational Site — Lyon
• GSK Investigational Site — Villejuif

Аргентина · 2 центра

• GSK Investigational Site — Rosario
• GSK Investigational Site — Viedma

Гонконг · 2 центра

• GSK Investigational Site — Pokfulam
• GSK Investigational Site — Shatin

Panama · 2 центра

• GSK Investigational Site — Panama City
• GSK Investigational Site — Panama City

Идентификаторы

NCT: NCT06551142 · 223054 · 2024-513663-10

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗