A Study to Test the Safety and Effectiveness of GSK5764227, Alone or With Other Treatments, in Participants With Advanced Gastrointestinal Cancers That Cannot be Surgically Removed (EMBOLD PanGI-201)

NCT06885034
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Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
346
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Lead sponsor
GlaxoSmithKline
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Start date
2025-06-11
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Number of sites
85
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Summary
This study will check how well a new medicine, Risvutatug rezetecan, (Ris-Rez, also known as GSK5764227) works, how safe it is and how the body handles it in participants all around the world with advanced inoperable or metastatic gastrointestinal cancer who have previously received treatment.
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Short title
A Study to Test the Safety and Effectiveness of GSK5764227, Alone or With Other Treatments, in Participants With Advanced Gastrointestinal Cancers That Cannot be Surgically Removed (EMBOLD PanGI-201)
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Official title
A Phase1 b/2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of GSK5764227 Alone and in Combination in Participants With Previously Treated Advanced Unresectable or Metastatic Gastrointestinal 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/Phase 2
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Study type
Interventional
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Completion date
2029-01-09
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First posted
2025-03-19
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Registry last updated
2026-10-19
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Primary completion date
2029-01-09
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Start date
2025-06-11
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Participants
346
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Participant count basis
Estimated
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Planned participants
346
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Protocol amendments
8
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Number of sites
85
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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
NCT06885034
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ClinicalTrials.gov ID
NCT06885034
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Confirmed Objective Response Rate (ORR)

    Timeframe: Up to approximately 22 months

    Confirmed ORR is defined as the proportion of participants who have achieved best overall response (BOR) of confirmed complete response (CR) or partial response (PR) as assessed by investigator, according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  1. Unconfirmed ORR

    Timeframe: Up to approximately 37 months

    Unconfirmed ORR is defined as the proportion of participants who have achieved a BOR of CR or PR as assessed by investigator, according to RECIST 1.1.

  2. Duration of Response (DoR)

    Timeframe: Up to approximately 37 months

    DoR is defined as the time from the date of the first documented objective response (CR/PR as assessed by investigator according to RECIST 1.1) until the date of the first documented progressive disease (PD) or death, whichever is earlier.

  3. Progression Free Survival (PFS)

    Timeframe: Up to approximately 37 months

    PFS (assessed by investigator), defined as the time from date of randomization (CRC) or the date of first dose of study intervention (PDAC) until the earliest date of documented disease progression per RECIST 1.1 or death due to any cause.

  4. Number of participants with AEs, serious adverse events (SAEs) and adverse events of special interest (AESIs) by severity

    Timeframe: Up to approximately 37 months

  5. Number of participants with AEs leading to dose modifications, discontinuation of study interventions or death

    Timeframe: Up to approximately 37 months

  6. Changes from baseline in vital signs: Temperature (degree Celsius)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  7. Changes from baseline vital signs: Respiratory rate (breaths per minute)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  8. Changes from baseline vital signs: Pulse rate (beats per minute)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  9. Changes from baseline vital signs: Blood pressure [millimetres of mercury (mmHg)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  10. Changes from baseline in hematology parameters: [White blood cell count (WBCs per microliter)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  11. Changes from baseline in hematology parameters: [Haemoglobin (Hgb) (grams per deciliter)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  12. Changes from baseline in hematology parameters:[Haematocrit (Proportion of red blood cells in blood)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  13. Changes from Baseline haematology parameter: [Red Blood Cell Count (RBC) (million cells per microliter)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  14. Changes from baseline haematology parameters: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per liter)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  15. Changes from Baseline haematology parameter: Platelet count (cells per microliter)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  16. Changes from baseline Clinical chemistry parameters: Total Protein, Albumin (Grams per deciliter)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  17. Changes from baseline Clinical Chemistry parameters: AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per liter)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

    Clinical chemistry parameters such as Aspartate Aminotransferase (AST) / Serum Glutamic-Oxaloacetic Transaminase (SGOT), Alanine Aminotransferase (ALT)/ Serum Glutamic-Pyruvic Transaminase and (SGPT), Alkaline phosphatase (ALP) and Creatinine Phosphokinase (CPK) will be analysed

  18. Changes from baseline Clinical Chemistry parameters: Total Bilirubin and Direct Bilirubin, Glucose, Calcium, Potassium, Sodium, Magnesium, Urea Nitrogen or urea, and Creatinine (milligrams per deciliter)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  19. Changes from baseline Clinical Chemistry parameters: Lactate dehydrogenase, Amylase and Lipase (units per liter)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  20. Changes from baseline Clinical Chemistry parameters: Chloride (millimoles per liter)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  21. Changes from baseline Clinical Chemistry parameters: Creatinine clearance (milliliters per minute)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  22. Changes from baseline cardiac function: Electrocardiogram (ECG) (milliseconds)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  23. Changes from baseline Eastern Cooperative Oncology Group performance status (ECOG-PS)

    Timeframe: Baseline (Day 1) and up to approximately 37 months

  24. Maximum observed concentration (Cmax) of Risvutatug Rezetecan (conjugated antibody)and GSK5757810 (small molecule toxin)

    Timeframe: Up to approximately 37 months

  25. Time to reach Cmax (Tmax) of Risvutatug Rezetecan (conjugated antibody) and GSK5757810 (small molecule toxin)

    Timeframe: Up to approximately 37 months

And 5 more, listed on the interactive page.

Sources for outcomes
clinicaltrials.gov

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

Participants are eligible to be included in the study only if all of the following criteria apply: All cohorts

  • Is at least 18 years of or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the informed consent form (ICF). CRC Cohort
  • Has histologically confirmed unresectable, locally advanced or unresectable metastatic adenocarcinoma of the colon or rectum (histology defined by World Health Organization (WHO) classification).

PDAC Cohort

  • Has histologically or cytologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of the pancreas (histology defined by WHO classification).

All Cohorts

  • Is willing to use adequate contraception.
  • Is capable of giving signed informed consent, including compliance with the requirements and restrictions listed in the ICF and in the protocol.
  • Has an ECOG performance status of 0 or 1.
  • Has adequate organ function.

Participants are excluded from the study if any of the following criteria apply:

  • Has a malignancy (except disease under study) that has progressed or required active treatment within the past 24 months except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas [e.g., breast, cervix, bladder] that have been resected with no evidence of disease.
  • Has had any major surgery within 28 days prior to randomization or first dose of study intervention, depending on sub-cohort/cohort assignment
  • Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
  • Has severe, uncontrolled or active cardiovascular disorders.
  • Has serious or poorly controlled hypertension.
  • Has clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose.
  • Has untreated brain or Central nervous system (CNS) metastases or brain/CNS metastases that have progressed.
  • Has 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 ongoing adverse reaction(s) from prior therapy that has(have) not recovered to Grade 1 or to the baseline status preceding prior therapy.
  • Has received any prior therapy with an Antibody-drug conjugate (ADC) with a Topoisomerase-1 (TOPO1)-inhibitor payload.
  • Is pregnant or breastfeeding.
Sources for eligibility
clinicaltrials.gov

  • GSK Investigational SiteLos Alamitos, United StatesRecruiting
  • GSK Investigational SiteLos Angeles, United StatesRecruiting
  • GSK Investigational SiteSanta Monica, United StatesRecruiting
  • GSK Investigational SiteWhittier, United StatesRecruiting
  • GSK Investigational SiteAurora, United StatesRecruiting
  • GSK Investigational SiteNew York, United StatesRecruiting
  • GSK Investigational SiteNew York, United StatesRecruiting
  • GSK Investigational SiteDurham, United StatesRecruiting
  • GSK Investigational SiteHouston, United StatesRecruiting
  • GSK Investigational SiteSan Antonio, United StatesRecruiting
  • GSK Investigational SiteWenatchee, United StatesRecruiting
  • GSK Investigational SiteMadison, United StatesRecruiting
  • GSK Investigational SiteHeidelberg, AustraliaRecruiting
  • GSK Investigational SiteMelbourne, AustraliaRecruiting
  • GSK Investigational SiteBonheiden, BelgiumRecruiting
  • GSK Investigational SiteBrussels, BelgiumRecruiting
  • GSK Investigational SiteLeuven, BelgiumRecruiting
  • GSK Investigational SiteRoeselare, BelgiumRecruiting
  • GSK Investigational SitePorto Alegre, BrazilRecruiting
  • GSK Investigational SiteSão Paulo, BrazilRecruiting
  • GSK Investigational SiteTeresina, BrazilRecruiting
  • GSK Investigational SiteCalgary, CanadaRecruiting
  • GSK Investigational SiteToronto, CanadaRecruiting
  • GSK Investigational SiteMontreal, CanadaRecruiting
  • GSK Investigational SiteSherbrooke, CanadaRecruiting

And 60 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2025
  • 2025-520672-26
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (2)