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

Official title

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

Overview

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

Interventions

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

Primary outcome measures

• Phase 1a: Number of participants with Adverse Events (AEs) [Time frame: Up to approximately 28 months]
• Phase 1a: Number of participants with Dose Limiting Toxicities (DLTs) [Time frame: Up to 21 days]
• Phase 1a: Number of participants with AEs, serious adverse events (SAEs) and adverse events of special interest (AESIs) by severity [Time frame: Up to approximately 30 months]
• Phase 1a: Number of participants with AEs leading to dose modifications [Time frame: 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 [Time frame: Up to approximately 28 months]
• Phase 1b: Confirmed Objective Response Rate (cORR) [Time frame: Up to approximately 27 months]

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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.

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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 15 centers

• 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
• … and 7 more centers

Spain · 9 centers

• 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
• … and 1 more center

Taiwan · 6 centers

• 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

United Kingdom · 6 centers

• 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

Canada · 5 centers

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

Japan · 5 centers

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

Israel · 4 centers

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

Italy · 4 centers

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

South Korea · 4 centers

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

France · 3 centers

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

Argentina · 2 centers

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

Hong Kong · 2 centers

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

Panama · 2 centers

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

Identifiers

NCT: NCT06551142 · 223054 · 2024-513663-10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗