Actinium Therapy for Late-stage Aggressive Sarcomas

NCT07156565 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: RTX-2358-101
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 6

Brief Summary

The goal of this clinical trial is to learn about the safety of drug \[Ac225\]RTX-2358 and the diagnostic imaging agent \[Cu64\]LNTH-1363S. Additionally Ratio Therapeutics will learn if \[Ac225\]RTX-2358 drug is effective in treating advanced sarcoma. The main questions the study aims to answer in Phase/Part 1 of the trial are:

• Is \[Ac225\]RTX-2358 tolerable or does it cause toxicities (medical problems) in patients.
• What is the most tolerable dose of \[Ac225\]RTX-2358
• Does the treatment show effectiveness on advanced sarcoma Participants will:
• Take drug \[Ac225\]RTX-2358 once every 8 weeks (4 cycle target; 6 cycle maximum) over a period of 12 months
• Visit the clinic three times for the first week of cycle one, then once a week for the remaining 7 weeks of cycle 1 for check-ups and tests.
• For cycles 2-6: patient will visit the clinic once every 2 weeks for checkups and tests
• Remain in long term follow-up for a period of four additional years

Conditions

Advanced Soft Tissue Sarcoma

Keywords

Radioligand Therapy; Sarcoma; Relapsed or refractory sarcoma; Soft tissue sarcoma; Radiopharmaceuticals; Theranostics; advanced soft tissue sarcoma

Outcome Measures

Primary Outcomes (2)

• Evaluate the safety (Frequency and severity of treatment emergent adverse events (TEAEs), Dose Limiting Toxicities (DLTs), serious adverse events (SAEs) and adverse events of special interest) of [Ac225-]RTX-2358

  Frequency and severity of treatment emergent adverse events (TEAEs), Dose Limiting Toxicities (DLTs), serious adverse events (SAEs) and adverse events of special interest (AESIs). Preliminary efficacy response across all cycles in Phase 1.

  48 weeks

• Determine the MTD of the administered activity of [Ac-225]RTX-2358 and select the administered activity for use in the expansion cohort

  Evaluate dose levels in Phase 1 escalating group design to identify the MTD and the administered activity to be used in the expansion cohort

  8 weeks

Secondary Outcomes (9)

• Determination the normal tissue radiation dosimetry of [Ac225]RTX-2358

  Day 1, 3, 8

• Evaluate the preliminary anti-tumor activity of [Ac225]RTX-2358 in patients with relapsed or refractory soft tissue sarcoma

  48 weeks

• Evaluate the preliminary anti-tumor activity of [Ac225]RTX-2358 in patients with relapsed or refractory soft tissue sarcoma

  48 weeks

• Evaluate the preliminary anti-tumor activity of [Ac225]RTX-2358 in patients with relapsed or refractory soft tissue sarcoma

  48 weeks

• Evaluate the safety and tolerability of [Cu-64]LNTH-1363S

  Up to 2 weeks after the [Cu64]LNTH-1363S injections

Study Arms (1)

Treatment with [Ac 225]RTX-2358

EXPERIMENTAL

The study design is a modified 3+3 with Phase 1 queue (IQ) escalating group design.

Drug: [Ac 225]RTX-2358; Diagnostic Test: [Cu64]LNTH-1363S

Interventions

[Ac 225]RTX-2358 DRUG

\[Ac225\]RTX-2358 will be given as an intravenous injection once every 8 weeks for up to 6 doses. Each group will receive a set administered activity level (dose) of \[Ac 225\]RTX 2358 given once every 8 weeks. The first group will received the lower dose, the second group will received the mid level dose, and the third group the highest dose. A Safety Review Committee will determine when/if it is appropriate to allow the next group to proceed.

Treatment with [Ac 225]RTX-2358

[Cu64]LNTH-1363S DIAGNOSTIC_TEST

\[Cu64\]LNTH-1363S is a investigational radioactive diagnostic imaging agent to demonstrate that the tumor expresses Fibroblast Activation Protein. An imaging test is performed after a single injection with \[Cu64\]LNTH-1363S 13-35 days before the first administration of study drug \[AC225\]RTX-2358 to confirm that the sarcoma has FAP expression.

Treatment with [Ac 225]RTX-2358

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older.
• History of relapse and refractory soft tissue sarcoma.
• Histological confirmation of sarcoma at any point since diagnosis
• At least 1 prior treatment regimen
• Measurable disease as per RECIST (v1.1) for soft tissue sarcoma that is also positive on FAPi PET/CT or PET/MRI scan.
• ECOG performance status of 0 or 1.
• Adequate Organ reserve and renal function as evidenced by:
• Neutrophil count ≥ 1200 µL without granulocyte colony stimulating factor
• Platelet count ≥ 100,000 µL
• Hemoglobin ≥ 8 g/dL
• Total bilirubin level ≤ 1.5 × upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
• Calculated creatinine clearance ≥ 60 mL/min. 6. Coagulation parameters (prothrombin time, international normalized ratio and activated partial thromboplastin time) ≤ 1.5 × ULN 7. All patients (males and females of childbearing potential) must agree to practice 2 forms of highly effective contraceptive precautions to prevent pregnancy from the time consent is signed and throughout the trial.
• \. The patient or the patient's legal representative must be willing and able to provide written informed consent.

You may not qualify if:

• History of whole pelvic irradiation.
• History of radioligand therapy.
• Treatment within 14 days prior to first administration with:
• Palliative surgery or external beam radiation.
• Approved anticancer therapy including chemotherapy or immunotherapy.
• Any investigational therapy.
• Any major surgery (e.g., requiring general anesthesia).
• Patients who are scheduled for external beam radiation therapy or radioligand therapy during the study period.
• Congestive heart failure \> Class II New York Heart Association Functional Classification, current pericarditis, myocardial infarction within 6 months, or symptomatic coronary artery disease.
• Patients with uncontrollable incontinence.
• Unstable or clinically significant concurrent medical condition that would, in the opinion of the Investigator, jeopardize the safety of a patient and/or their compliance with the protocol.
• Active infection requiring systemic antibacterial/antibiotic, antifungal, or antiviral therapy. Chronic antiviral therapy for stable viral disease can be included.
• History of active fibrotic condition.
• Any active malignancy other than sarcoma that requires treatment.
• Stable brain metastasis is allowed but documented untreated metastases to brain or meninges are excluded.

Sponsors & Collaborators

• Ratio Therapeutics, Inc.: lead

Study Sites (6)

UCLA

Los Angeles, California, 90095, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Memorial Sloane Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Case Western

Cleveland, Ohio, 44106, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77230, United States

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

NOT YET RECRUITING

MeSH Terms

Conditions

Sarcoma; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The Phase 1 portion of the study is a modified "3+3" dose escalation with Phase 1 queue (IQ) design planned for 3 cohorts/groups/dose levels, with potential backfill in administered activity cohorts.

Study Record Dates

• First Submitted: January 17, 2025
• First Posted: September 5, 2025
• Study Start: November 12, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2032
• Last Updated: March 17, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (5)