Phase 1b/2 Evaluation of Efficacy and Safety of GSK5764227 in Adults with Relapsed/Refractory Unresectable Advanced Osteosarcoma or Metastatic Soft‑Tissue Sarcoma

Primary objective:

• Evaluate the clinical efficacy of Ris‑Rez in participants with unresectable relapsed/refractory osteosarcoma (Cohort 1) who have progressed after or are intolerant to at least one prior systemic therapy.
• Evaluate the clinical efficacy of Ris‑Rez in participants with unresectable advanced or metastatic soft tissue sarcoma (Cohort 2) following progression on or intolerance to at least one prior systemic therapy.

The trial enrolled 54 participants diagnosed with Sarcoma, comprising both male and female patients aged 12 years and older, including adolescents classified as vulnerable. All subjects had histologically confirmed unresectable advanced or metastatic osteosarcoma or soft‑tissue sarcoma that progressed after at least one prior systemic therapy. Enrollment required an ECOG performance status of 0‑1 (or Lansky/Karnofsky score ≥70 % for adolescents) and adequate organ function, with no deterioration in performance status during the two weeks preceding randomization. Selection was based on documented disease progression confirmed by radiological imaging and adherence to informed‑consent requirements.

The study is an integrated Phase 1b/2, open‑label clinical trial assessing the efficacy and safety of the investigational agent Risvutatug Rezetecan (Ris‑Rez) in participants with previously treated unresectable advanced or metastatic sarcoma. Eligible participants are assigned to one of two disease‑specific cohorts (relapsed/refractory osteosarcoma or soft‑tissue sarcoma) after confirmation of histology, documented disease progression following at least one prior systemic therapy, and adequate performance status (ECOG 0–1 or equivalent). The trial schedule comprises an initial screening visit to verify inclusion criteria, a baseline visit on Day 1 of Cycle 1 during which the intravenous infusion of GSK5764227 is administered, subsequent treatment cycles administered at predefined intervals, and scheduled follow‑up assessments (including imaging for tumor response) at regular intervals up to week 18, which corresponds to the primary efficacy assessment time point. An end‑of‑study visit is performed after the final efficacy assessment or earlier if discontinuation criteria are met. Participants remain in the study for a minimum of 18 weeks and may continue observation until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. The primary endpoints are progression free survival rate at week 18 and confirmed overall response rate, both evaluated per RECIST 1.1. The overall trial period extends from the projected recruitment start on 29 June 2026 to the anticipated completion date of 17 December 2029.

The investigational product, identified as intravenous GSK5764227, is supplied as a powder for solution for infusion. The preparation is reconstituted according to the study protocol and administered by infusion through a venous route. The specific dose amount, concentration, and infusion duration are defined in the dosing schedule and are adjusted based on participant weight and clinical parameters. Administration occurs on a predefined schedule, with each infusion given on the days stipulated by the protocol.

Administration details include:

• Reconstitution of the powder immediately prior to infusion.
• Infusion performed in a clinical setting by qualified personnel.
• Monitoring of vital signs and infusion-related reactions during and after the procedure.
• Documentation of compliance with the dosing schedule in the case report form.

Efficacy will be evaluated using two primary endpoints. The first endpoint is Progression free survival rate at week 18 (PFS18), which will be assessed by the investigator according to RECIST 1.1. The second endpoint is the confirmed overall response rate (ORR), defined as the proportion of participants achieving a confirmed complete response (CR) or partial response (PR) as assessed by the investigator using the same RECIST 1.1 criteria.