Last updated: 07/30/2026 18:20:27
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)
GSK study ID
223675
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Trial status
Recruiting
Recruiting
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Confirmed Objective Response Rate (ORR)
Timeframe: Up to approximately 22 months
Secondary outcomes:
Unconfirmed ORR
Timeframe: Up to approximately 37 months
Duration of Response (DoR)
Timeframe: Up to approximately 37 months
Progression Free Survival (PFS)
Timeframe: Up to approximately 37 months
Number of participants with AEs, serious adverse events (SAEs) and adverse events of special interest (AESIs) by severity
Timeframe: Up to approximately 37 months
Number of participants with AEs leading to dose modifications, discontinuation of study interventions or death
Timeframe: Up to approximately 37 months
Changes from baseline in vital signs: Temperature (degree Celsius)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from baseline vital signs: Respiratory rate (breaths per minute)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from baseline vital signs: Pulse rate (beats per minute)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from baseline vital signs: Blood pressure [millimetres of mercury (mmHg)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from baseline in hematology parameters: [White blood cell count (WBCs per microliter)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from baseline in hematology parameters: [Haemoglobin (Hgb) (grams per deciliter)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from baseline in hematology parameters:[Haematocrit (Proportion of red blood cells in blood)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from Baseline haematology parameter: [Red Blood Cell Count (RBC) (million cells per microliter)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from baseline haematology parameters: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per liter)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from Baseline haematology parameter: Platelet count (cells per microliter)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from baseline Clinical chemistry parameters: Total Protein, Albumin (Grams per deciliter)
Timeframe: Baseline (Day 1) and up to approximately 37 months
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
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
Changes from baseline Clinical Chemistry parameters: Lactate dehydrogenase, Amylase and Lipase (units per liter)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from baseline Clinical Chemistry parameters: Chloride (millimoles per liter)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from baseline Clinical Chemistry parameters: Creatinine clearance (milliliters per minute)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from baseline cardiac function: Electrocardiogram (ECG) (milliseconds)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Changes from baseline Eastern Cooperative Oncology Group performance status (ECOG-PS)
Timeframe: Baseline (Day 1) and up to approximately 37 months
Maximum observed concentration (Cmax) of Risvutatug Rezetecan (conjugated antibody), GSK5757810 (small molecule toxin) and Drug 4
Timeframe: Up to approximately 37 months
Time to reach Cmax (Tmax) of Risvutatug Rezetecan (conjugated antibody), GSK5757810 (small molecule toxin) and Drug 4
Timeframe: Up to approximately 37 months
Area under the concentration-time curve (AUC) of Risvutatug Rezetecan (conjugated antibody),GSK5757810 (small molecule toxin) and Drug 4
Timeframe: Up to approximately 37 months
Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb)
Timeframe: Up to approximately 37 months
Titers of ADA against GSK5764227
Timeframe: Up to approximately 37 months
Number of participants with symptomatic AEs, by severity, as measured by Patient Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Timeframe: Up to approximately 37 months
Level of bother of AEs as measured by Functional Assessment of Cancer Therapy – Item GP5 (FACT-GP5)
Timeframe: Up to approximately 37 months
Interventions:
Biological/vaccine: Risvutatug Rezetecan
Drug: Drug 1
Drug: Drug 2
Drug: Drug 3
Drug: Drug 4
Enrollment:
451
Observational study model:
Not applicable
Primary completion date:
2028-10-01
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Gastrointestinal Neoplasms
Product
GSK5764227
Collaborators
Not applicable
Study date(s)
June 2025 to January 2029
Type
Interventional
Phase
1/2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Participants are eligible to be included in the study only if all of the following criteria apply:
- Is at least 18 or the legal age of consent in the jurisdiction in which the study is taking place years of age at the time of signing the informed consent form (ICF).
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- Participants are eligible to be included in the study only if all of the following criteria apply:
- Is at least 18 or the legal age of consent in the jurisdiction in which the study is taking place years of age 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.
Exclusion criteria:
- 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.
Trial location(s)
Location
GSK Investigational Site
SEOUL, Seoul Teugbyeolsi, South Korea, 110 744
Status
Recruiting
Location
GSK Investigational Site
Punta Pacifica Panama City Panama, Panama, N/A
Status
Recruiting
Location
GSK Investigational Site
La Villa de los Santos, Los Santos, Panama, 6040
Status
Recruiting
Study documents
No study documents available.
Results overview
Study Results yet to be posted
Recruitment status
Recruiting
Actual primary completion date
Not applicable
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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