(P 430) A PH/2 STUDY OF THE RADIOPHARMACEUTICAL [AC-225]RTX-2358 IN THE TREATMENT OF RELAPSED / REFRACTORY (R/R) SOFT TISSUE SARCOMA (STS) THE ATLAS STUDY - ACTINIUM THERAPY FOR LATE-STAGE AGGRESSIVE SARCOMAS

Objective: STUDY OVERVIEW
ATLAS is a seamless Ph1/2 clinical study to evaluate safety, tolerability, dosimetry, biodistribution, PK and anti-tumor activity of [Ac-225]RTX-2358 in adult patients with R/R STS.

Methods: RATIONALE
Fibroblast Activation Protein (FAP) is expressed on the surface of cancer-associated fibroblasts (CAFs) with minimal normal tissue expression and is involved in the formation, maintenance, and spread of tumors. Sarcomas frequently demonstrate high FAP expression on tumor cells themselves in contrast to other solid tumors, where it is mainly expressed on CAFs within the tumor stroma.

Radioligand therapies utilizing alpha emitters, specifically Ac-225, have emerged as a treatment strategy in oncology. Ac-225 and its daughter radionuclides emit high-energy alpha particles capable of inducing double-stranded DNA breaks, leading to significant cytotoxic effects within cells. Clinical investigations of Ac-225-labeled compounds have shown promising outcomes, particularly in settings where traditional therapies have failed.

STUDY MEDICATION
[Ac-225]RTX-2358 (Ratio Therapeutics, Boston) has been designed to have high affinity to FAP, translating into extended tumor residence times. This enhanced binding characteristic may lead to increased therapeutic efficacy by sustained cytotoxic radiation delivery directly at the FAP expressing tumor cells. The selective binding to FAP results in low levels of [Ac-225]RTX-2358 binding to normal tissue.

STUDY DESIGN
Patients will be treated in 3 dose escalation cohorts (7.5, 11.25, 15 MBq) with up to 6 cycles of [Ac-225]RTX-2358 in a 3 x 3 dose escalation design (up to 26 patients) and subsequent Ph2 expansion cohort (up to 50 patients). Dose escalation / de-escalation decisions will be made by a Safety Review Committee.

PATIENT POPULATION
Patients over 18 yrs with a history of histologically confirmed R/R STS (measurable disease per RECIST v1.1) are eligible if they have a positive screening [Cu-64] FAP PET, with an SUV mean ≥ 2 in at least one tumor site, an ECOG 0 to 1, and adequate organ reserve and renal function.

Results: N/A

Conclusion: N/A