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)

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

Overview

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.

Interventions

• Biological Risvutatug Rezetecan
  Risvutatug Rezetecan will be administered
• Drug Drug 1
  Drug 1 will be administered
• Drug Drug 2
  Drug 2 will be administered
• Drug Drug 3
  Drug 3 will be administered
• Drug Drug 4
  Drug 4 will be administered

Primary outcome measures

• Confirmed Objective Response Rate (ORR) [Time frame: Up to approximately 22 months]

Secondary outcome measures (12)

• Unconfirmed ORR [Time frame: Up to approximately 37 months]
• Duration of Response (DoR) [Time frame: Up to approximately 37 months]
• Progression Free Survival (PFS) [Time frame: Up to approximately 37 months]
• Number of participants with AEs, serious adverse events (SAEs) and adverse events of special interest (AESIs) by severity [Time frame: Up to approximately 37 months]
• Number of participants with AEs leading to dose modifications, discontinuation of study interventions or death [Time frame: Up to approximately 37 months]
• Changes from baseline in vital signs: Temperature (degree Celsius) [Time frame: Baseline (Day 1) and up to approximately 37 months]
• Changes from baseline vital signs: Respiratory rate (breaths per minute) [Time frame: Baseline (Day 1) and up to approximately 37 months]
• Changes from baseline vital signs: Pulse rate (beats per minute) [Time frame: Baseline (Day 1) and up to approximately 37 months]
• Changes from baseline vital signs: Blood pressure [millimetres of mercury (mmHg) [Time frame: Baseline (Day 1) and up to approximately 37 months]
• Changes from baseline in hematology parameters: [White blood cell count (WBCs per microliter) [Time frame: Baseline (Day 1) and up to approximately 37 months]
• Changes from baseline in hematology parameters: [Haemoglobin (Hgb) (grams per deciliter) [Time frame: Baseline (Day 1) and up to approximately 37 months]
• Changes from baseline in hematology parameters:[Haematocrit (Proportion of red blood cells in blood) [Time frame: Baseline (Day 1) and up to approximately 37 months]

Eligibility 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.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 12 centers

• GSK Investigational Site — Los Alamitos
• GSK Investigational Site — Los Angeles
• GSK Investigational Site — Santa Monica
• GSK Investigational Site — Whittier
• GSK Investigational Site — Aurora
• GSK Investigational Site — New York
• GSK Investigational Site — New York
• GSK Investigational Site — Durham
• … and 4 more centers

France · 8 centers

• GSK Investigational Site — Dijon
• GSK Investigational Site — Marseille
• GSK Investigational Site — Paris
• GSK Investigational Site — Paris
• GSK Investigational Site — Paris
• GSK Investigational Site — Poitiers
• GSK Investigational Site — Rennes
• GSK Investigational Site — Villejuif

Spain · 8 centers

• GSK Investigational Site — Barcelona
• GSK Investigational Site — HebrOn
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid
• GSK Investigational Site — Pamplona
• GSK Investigational Site — Santander
• GSK Investigational Site — Zaragoza

Japan · 6 centers

• GSK Investigational Site — Aichi
• GSK Investigational Site — Chiba
• GSK Investigational Site — Hokkaido
• GSK Investigational Site — Osaka
• GSK Investigational Site — Tokyo
• GSK Investigational Site — Tokyo

Germany · 5 centers

• GSK Investigational Site — Bochum
• GSK Investigational Site — Düsseldorf
• GSK Investigational Site — Frankfurt
• GSK Investigational Site — Lübeck
• GSK Investigational Site — München

Mexico · 5 centers

• GSK Investigational Site — Tuxtla Gutiérrez
• GSK Investigational Site — Cuernavaca
• GSK Investigational Site — Mexico City
• GSK Investigational Site — Mexico City
• GSK Investigational Site — San Pedro Garza García

Belgium · 4 centers

• GSK Investigational Site — Bonheiden
• GSK Investigational Site — Brussels
• GSK Investigational Site — Leuven
• GSK Investigational Site — Roeselare

Canada · 4 centers

• GSK Investigational Site — Calgary
• GSK Investigational Site — Toronto
• GSK Investigational Site — Montreal
• GSK Investigational Site — Sherbrooke

Finland · 4 centers

• GSK Investigational Site — Helsinki
• GSK Investigational Site — Helsinki
• GSK Investigational Site — Kuopio
• GSK Investigational Site — Tampere

Italy · 4 centers

• GSK Investigational Site — Milan
• GSK Investigational Site — Milan
• GSK Investigational Site — Pisa
• GSK Investigational Site — Roma

Netherlands · 4 centers

• GSK Investigational Site — Amsterdam
• GSK Investigational Site — Maastricht
• GSK Investigational Site — Rotterdam
• GSK Investigational Site — Utrecht

Sweden · 4 centers

Center list to be confirmed — check the primary protocol.

Brazil · 3 centers

• GSK Investigational Site — Porto Alegre
• GSK Investigational Site — São Paulo
• GSK Investigational Site — Teresina

Norway · 3 centers

• GSK Investigational Site — Lrenskog
• GSK Investigational Site — Oslo
• GSK Investigational Site — Stavanger

Poland · 3 centers

• GSK Investigational Site — Brzozów
• GSK Investigational Site — Koszalin
• GSK Investigational Site — Warsaw

South Korea · 3 centers

• GSK Investigational Site — Seoul
• GSK Investigational Site — Seoul
• GSK Investigational Site — Seoul

Australia · 2 centers

• GSK Investigational Site — Heidelberg
• GSK Investigational Site — Melbourne

Panama · 2 centers

• GSK Investigational Site — La Villa de Los Santos
• GSK Investigational Site — Punta Pacifica Panama City Panama

United Kingdom · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06885034 · 223675 · 2025-520672-26-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗