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

NCT06551142
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
845
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Lead sponsor
GlaxoSmithKline
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Start date
2024-09-30
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Number of sites
67
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Summary
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
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Acronym
PanTumor-101
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Short title
A Study of GSK5764227 in Participants With Advanced Solid Tumors (EMBOLD)
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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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2029-06-08
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First posted
2024-08-13
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Registry last updated
2026-05-22
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Primary completion date
2028-10-16
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Start date
2024-09-30
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Participants
845
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Participant count basis
Estimated
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Planned participants
845
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Protocol amendments
7
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Number of sites
67
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
GlaxoSmithKline
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06551142
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ClinicalTrials.gov ID
NCT06551142
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
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  1. Phase 1a: Number of participants with Adverse Events (AEs)

    Timeframe: Up to approximately 28 months

  2. Phase 1a: Number of participants with Dose Limiting Toxicities (DLTs)

    Timeframe: Up to 21 days

  3. Phase 1a: Number of participants with AEs, serious adverse events (SAEs) and adverse events of special interest (AESIs) by severity

    Timeframe: Up to approximately 30 months

  4. Phase 1a: Number of participants with AEs leading to dose modifications

    Timeframe: Up to approximately 28 months

  5. Phase 1a: Number of participants with changes in vital signs, body weight, laboratory tests, electrocardiogram (ECG) and Eastern Cooperative Oncology Group (ECOG) performance status

    Timeframe: Up to approximately 28 months

  6. Phase 1b: Confirmed Objective Response Rate (cORR)

    Timeframe: Up to approximately 27 months

    cORR is defined as the proportion of participants who have confirmed Complete response (CR) or Partial response (PR), assessed by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) criteria or other imaging criteria for defined tumor types.

  1. Phase 1a and Phase 1b: Maximum concentration (Cmax) of Ris-Rez

    Timeframe: Up to approximately 28 months

  2. Phase 1a and Phase 1b: Time to reach maximum concentration (Tmax) of Ris-Rez

    Timeframe: Up to approximately 28 months

  3. Phase 1a and Phase 1b: Area under the curve (AUC) of Ris-Rez

    Timeframe: Up to approximately 28 months

  4. Phase 1a and Phase 1b: Trough concentration (Ctrough) of Ris-Rez (conjugated antibody)

    Timeframe: Up to approximately 28 months

  5. Phase 1a and Phase 1b: Trough concentration (Ctrough) of Ris-Rez (total antibody)

    Timeframe: Up to approximately 28 months

  6. Phase 1a and Phase 1b: Trough concentration (Ctrough) of GSK5757810 (small-molecule toxin)

    Timeframe: Up to approximately 28 months

  7. Phase 1a: Confirmed Objective Response Rate (cORR)

    Timeframe: Up to approximately 33 months

    cORR is defined as the proportion of participants who have confirmed CR or PR, per RECIST V1.1 by investigator

  8. Phase 1a: Disease control rate at 12 weeks (DCR12)

    Timeframe: At 12 weeks

    DCR is defined as the proportion of participants who have achieved CR, PR or Stable disease (SD) ≥11 weeks per RECIST v1.1 by investigator assessment

  9. Phase 1b: Disease control rate at 12 weeks (DCR12)

    Timeframe: At 12 weeks

    DCR defined as the proportion of participants who have achieved CR, PR or SD ≥11 weeks per RECIST 1.1 or other imaging criteria for defined tumor types by investigator.

  10. Phase 1a: Duration of Response (DoR)

    Timeframe: Up to approximately 33 months

    DoR is defined as the date of first documented objective response (CR/PR) until per RECIST 1.1 by investigator assessment to the date of first documented PD or death due to any cause, whichever comes first.

  11. Phase 1b: Duration of Response (DoR)

    Timeframe: Up to approximately 33 months

    DoR defined as the time from the date of first documented objective response (CR/PR) per RECIST 1.1 or other imaging criteria for defined tumor types by investigator assessment to the date of first documented PD or death due to any cause, whichever comes first.

  12. Phase 1b: Proportion of Participants with Tumour antigen Decrease From Baseline >=50% response rate

    Timeframe: Up to approximately 33 months

    Tumour antigen response rate is defined as a proportion of participants with ≥50% decrease from baseline in the tumour antigen during the study. Any observed ≥50% decrease will be confirmed by repeat assessment after approximately 3 weeks

  13. Phase 1a and Phase 1b: Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb)

    Timeframe: Up to approximately 30 months

  14. Phase 1a and Phase 1b: Titers of ADA against Ris-Rez

    Timeframe: Up to approximately 30 months

  15. Phase 1b: Number of participants with AEs, SAEs and AESI by severity

    Timeframe: Up to approximately 30 months

  16. Phase 1b: Number of participants with AEs leading to dose modifications

    Timeframe: Up to approximately 27 months

  17. Phase 1b: Number of participants with changes in vital signs, body weight, laboratory tests, ECG, ECHO and ECOG performance status

    Timeframe: Up to approximately 28 months

  18. Phase 1b: Progression-Free Survival (PFS)

    Timeframe: Up to approximately 33 months

    PFS is defined as the time from randomization (dose optimization), or time from first dose where there is no randomization (dose expansion) until the earliest date of documented disease progression (investigator-assessed according to RECIST 1.1 or other imaging criteria for defined tumor types) or death due to any cause.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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:

  1. Participants with advanced/metastatic solid tumors.

  2. For monotherapy dose escalation: participants must have progressed on or become intolerant to all available SOC therapies.

  3. 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.

  • 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:

    1. Has QT interval, corrected for heart rate (QTc) >450 msec or QTc >480 msec for participants with bundle branch block.
    2. 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).
    3. 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.
    4. 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.

Sources for eligibility
clinicaltrials.gov

  • GSK Investigational SiteStanford, United StatesRecruiting
  • GSK Investigational SiteDenver, United StatesRecruiting
  • GSK Investigational SiteNew Haven, United StatesRecruiting
  • GSK Investigational SiteFort Wayne, United StatesRecruiting
  • GSK Investigational SiteBoston, United StatesRecruiting
  • GSK Investigational SiteDetroit, United StatesRecruiting
  • GSK Investigational SiteNew Brunswick, United StatesRecruiting
  • GSK Investigational SiteMyrtle Beach, United StatesRecruiting
  • GSK Investigational SiteNashville, United StatesRecruiting
  • GSK Investigational SiteAustin, United StatesRecruiting
  • GSK Investigational SiteDallas, United StatesRecruiting
  • GSK Investigational SiteSan Antonio, United StatesRecruiting
  • GSK Investigational SiteTyler, United StatesRecruiting
  • GSK Investigational SiteWest Valley City, United StatesRecruiting
  • GSK Investigational SiteNorfolk, United StatesRecruiting
  • GSK Investigational SiteRosario, ArgentinaCompleted
  • GSK Investigational SiteViedma, ArgentinaRecruiting
  • GSK Investigational SiteHamilton, CanadaRecruiting
  • GSK Investigational SiteOttawa, CanadaRecruiting
  • GSK Investigational SiteToronto, CanadaRecruiting
  • GSK Investigational SiteMontreal, CanadaRecruiting
  • GSK Investigational SiteSherbrooke, CanadaRecruiting
  • GSK Investigational SiteBordeaux, FranceRecruiting
  • GSK Investigational SiteLyon, FranceRecruiting
  • GSK Investigational SiteVillejuif, FranceRecruiting

And 42 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2024-513663-10
Sources for references
clinicaltrials.gov

Related records

Drugs (9)

Lead sponsors (1)

Targets (8)