Evaluation of efficacy and safety of GSK5764227 (alone and in combination) in participants with previously treated advanced unresectable or metastatic gastrointestinal solid tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Sep 2025 → ongoing

Decision date (initial)

2025-08-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2025-520672-26-00

ClinicalTrials.gov

NCT06885034

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacodynamic, Therapy, Safety

Part 1A (CRC): CRC-A
To evaluate the clinical efficacy of two Q3W doses of GSK5764227 in participants with advanced unresectable CRC.
Part 1A (CRC): CRC-B
To evaluate the clinical efficacy of two Q2W doses of GSK5764227 in participants with advanced, unresectable CRC.
Part 1B (PDAC):
To evaluate the clinical efficacy of GSK5764227 in participants with advanced, unresectable PDAC

Conditions and MedDRA coding

Gastrointestinal Neoplasms

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. All cohorts: 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 ICF
2. Cohort A (CRC) Part 1A Participants only: Has histologically confirmed unresectable, locally advanced or unresectable metastatic adenocarcinoma of the colon or rectum (histology defined by WHO classification).
3. Cohort A (CRC) Part 1A Participants only: Must have received 1-2 lines of systemic treatment for advanced CRC including the following: a fluoropyrimidine, oxaliplatin and/or irinotecan, an anti-VEGF monoclonal antibody and/or an anti-EGFR monoclonal antibody, if the approved biologic therapy(ies) is available.
4. Cohort A (CRC) Part 1A Participants only: Must provide tumor tissue from a newly obtained fresh biopsy or an archival tumor tissue.
5. Cohort B (PDAC) Part 1B Participants only: Has histologically or cytologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of the pancreas (histology defined by WHO classification).
6. Cohort B (PDAC) Part 1B Participants only: Must have received 1 and no more than 1 line of therapy for advanced PDAC, with documented progression.
7. Cohort B (PDAC) Part 1B Participants only: Should provide tumor tissue at screening, where available or medically feasible.
8. All cohorts: Has at least 1 target lesion per RECIST 1.1
9. Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before randomization (CRC-A and CRC-B) or before first dose of study intervention (Cohort B)
10. Has adequate organ function as defined in the protocol

Exclusion criteria 8

1. Has had any major surgery within 28 days prior to randomization (CRC-A and CRC-B) or before first dose of study intervention (Cohort B)
2. Has severe, uncontrolled or active cardiovascular disorders
3. Has serious or poorly controlled hypertension
4. Has clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose.
5. Has untreated brain or CNS metastases or brain/CNS metastases that have progressed.
6. Principal Exclusion Criteria Has current active pneumonitis or any history of pneumonitis requiring steroids or immunomodulatory treatment within 90 days of planned randomization (CRC-A and CRC-B) or planned first dose of study intervention (Cohort B) or any history of drug-induced pneumonitis.
7. Has ongoing adverse reaction(s) from prior therapy that has(have) not recovered to Grade 1 or to the baseline status preceding prior therapy
8. Has received any prior therapy with an ADC with a TOPO1-inhibitor payload

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Confirmed ORR, defined as the proportion of participants who have achieved BOR of confirmed CR or PR as assessed by investigator, according to RECIST 1.1.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

79 New Oxford Street

City

London

Postcode

WC1A 1DG

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 22

Locations

10 EU/EEA countries · 59 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 163 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications