A Study Evaluating the Efficacy and Safety of Risvutatug Rezetecan in Participants With Advanced Sarcomas (EMBOLD Sarcoma-202)

Phase 1b/2 Study Evaluating the Efficacy and Safety of Risvutatug Rezetecan in Participants With Previously Treated Unresectable Advanced or Metastatic Sarcomas

The main goal of this study is to test a new medicine, Risvutatug Rezetecan also called Ris-Rez. We want to see if this medicine can help people with certain types of cancer, whether its safe to use, how well people tolerate it, and how their bodies handle the drug (how its absorbed and broken down). This research is for adolescents and adults who have either: Osteosarcoma, which is a type of bone cancer, or Soft Tissue Sarcoma, which is a type of cancer that starts in soft body tissues (like muscle, fat, or nerves). In both cancer types the cancer must have already been treated, but has come back or spread, and cant be removed by surgery

Study Overview

• Status: Not yet recruiting
• Conditions: Sarcoma
• Intervention / Treatment: Biological: Ris-Rez; Biological: G-CSF

• Study Type: Interventional
• Enrollment (Estimated): 113
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

• Participants must be ≥ 12 years of age.
• Has histologically confirmed unresectable advanced or metastatic R/R OSA (Cohort 1) or unresectable advanced or metastatic STS (Cohort 2) that has progressed to at least one prior line of systemic therapy.
• Has documented disease progression on the last line of systemic treatment as confirmed by radiological imaging
• Has an ECOG performance status of 0 or 1, or Lansky PS/Karnofsky PS ≥ 70% for adolescent participants, with no deterioration in the 2 weeks prior to first dose/randomization.
• Has adequate organ function.
• All participants, or their legal guardians, must provide signed informed consent and agree to follow the study protocol before starting any study activities

Exclusion Criteria:

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

• Has received any prior therapy with an Antibody-drug-conjugates (ADC) with a TOPO1-inhibitor payload.
• Has known sensitivity to study intervention components or excipients or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
• Has severe, uncontrolled or active cardiovascular disorders.
• Known active infectious diseases requiring systemic treatment or known Human immunodeficiency virus (HIV).
• Has symptomatic brain metastases or untreated progression exclusively due to brain metastasis during or after the last treatment prior to screening, evidence of leptomeningeal/meningeal/brainstem metastasis or evidence of spinal cord metastases.
• Has received treatment with an investigational agent within 4 weeks of the first dose of study intervention.
• Is pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1A (Ris-Rez)	Biological: Ris-Rez; Ris-Rez will be administered
Experimental: Cohort 1B [Ris-Rez + Granulocyte-Colony Stimulating Factor (G-CSF)]	Biological: Ris-Rez; Ris-Rez will be administered; Biological: G-CSF; G-CSF will be administered
Experimental: Cohort 2 (Ris-Rez)	Biological: Ris-Rez; Ris-Rez will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1: Progression free survival rate at Week18 (PFS18)	PFS is defined as the time from the date of randomization until the date of documented disease progression or death due to any cause, whichever occurs first, as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)	At Week 18
Cohort 1 & 2: Confirmed Objective Response Rate (ORR)	Confirmed ORR is defined as the proportion of participants who have achieved a confirmed Complete Response (CR) or Partial Response PR as assessed by investigator, according to RECIST 1.1	Up to approximately 98 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1 & 2: Number of participants with Adverse events (AEs) and serious AEs (SAEs) by severity		Up to approximately 179 weeks
Cohort 1 & 2: Number of participants with AEs/SAEs leading to dose modifications or study intervention discontinuation or death		Up to approximately 179 weeks
Cohort 1 & 2: Number of participants with a change from baseline in vital signs	Number of participants will be assessed	Baseline (Day-1) and up to approximately 179 weeks
Cohort 1 & 2: Number of participants with a change from baseline in body weight	Number of participants will be assessed	Baseline (Day-1) and up to approximately 179 weeks
Cohort 1 & 2: Number of participants with a change from baseline in laboratory parameters (haematology and clinical chemistry)	Number of participants will be assessed	Baseline (Day-1) and up to approximately 179 weeks
Number of participants with a change from baseline in cardiac function [Electrocardiogram (ECG)]	Number of participants will be assessed	Baseline (Day-1) and up to approximately 179 weeks
Number of participants with a change from baseline in Eastern Cooperative Oncology Group (ECOG) performance status	Number of participants will be assessed	Baseline (Day-1) and up to approximately 179 weeks
Cohort 2: PFS rate at Week 18 (PFS18)	PFS is defined as the time from the date of randomization until the date of documented disease progression or death due to any cause, whichever occurs first, as assessed by the investigator according to RECIST 1.1	At Week 18
Cohort 1 & 2: Duration of response (DoR)	DoR is defined as the time from the date of the first documented objective response (CR/PR) that is subsequently confirmed, until the date of the first documented PD or death, whichever is earlier, as assessed by investigator according to RECIST 1.1	Up to approximately 179 weeks
Cohort 1 & 2: PFS rate at Week 30 (PFS30)	PFS is defined as the time from the date of randomization until the date of documented disease progression or death due to any cause, whichever occurs first, as assessed by the investigator according to RECIST 1.1	At Week 30
Cohort 1 & 2: PFS	PFS is defined as the time from the date of randomization until the date of documented disease progression or death due to any cause, whichever occurs first, as assessed by the investigator according to RECIST 1.1	Up to approximately 179 weeks
Cohort 1 & 2: Unconfirmed ORR	Unconfirmed ORR is defined as the proportion of participants who have achieved a response of CR or PR (without confirmation) as assessed by the investigator according to RECIST 1.1.	Up to approximately 179 weeks
Cohort 1 & 2: Observed pharmacokinetic (PK) concentration of Ris-Rez (conjugated antibody) and payload		Up to approximately 179 weeks
Cohort 1 & 2: Proportion of participants with positive and total Antidrug antibody (ADA) and Neutralizing Antibody (NAb) against Ris-Rez		Up to approximately 179 weeks
Cohort 1 & 2: Titers of ADA against Ris-Rez		Up to approximately 179 weeks
Cohort 1 & 2: Participant-reported experience on study treatment	Number of participants who reported their experience with study treatment using validated questionnaires will be measured	Up to approximately 179 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Estimated): July 14, 2026
• Primary Completion (Estimated): December 10, 2027
• Study Completion (Estimated): December 17, 2029

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 19, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Sarcoma; Risvutatug Rezetecan; Ris-Rez; EMBOLD Sarcoma-202
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Sarcoma; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Carbohydrates; Intercellular Signaling Peptides and Proteins; Glycoproteins; Glycoconjugates; Colony-Stimulating Factors; Hematopoietic Cell Growth Factors; Cytokines; Granulocyte Colony-Stimulating Factor
• Other Study ID Numbers: 300640; 2025-523997-18 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No