Actinium-based treatment for late-stage aggressive soft tissue sarcoma
A Seamless Phase 1/2 Open-label Study to Evaluate the Safety, Determine the Maximum Tolerated Dose of Administered Activity, and Evaluate the Efficacy of the Therapeutic Radiopharmaceutical [Ac 225]-RTX-2358 in the Treatment of Relapsed or Refractory Sarcoma
This treatment will try an actinium-based radioligand drug together with a PET imaging agent in adults with relapsed or treatment-resistant soft tissue sarcoma to see if it is safe and can shrink tumors.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Ratio Therapeutics, Inc. Industry-sponsored |
| Drugs / interventions | chemotherapy, immunotherapy, radiation |
| Locations | 6 sites (Los Angeles, California and 5 other locations) |
| Trial ID | NCT07156565 on ClinicalTrials.gov |
What this trial studies
RTX-2358-101 is a Phase 1 dose-escalation study of [Ac-225]RTX-2358 given with [Cu-64]LNTH-1363S PET imaging in adults with relapsed or refractory soft tissue sarcoma. The Phase 1 portion uses a modified 3+3 ascending administered-activity design across three cohorts to determine the most tolerable dose while monitoring safety, dosimetry, biodistribution, and pharmacokinetics. Each treatment cycle consists of a single injection on Day 1 followed by eight weeks of monitoring, with a target of four cycles (up to six) and long-term follow-up for four years. Eligibility requires measurable RECIST v1.1 disease that is FAPi PET-positive, ECOG 0–1, adequate organ function, and at least one prior therapy.
Who should consider this trial
Good fit: Adults (≥18) with measurable, relapsed or refractory soft tissue sarcoma that is FAPi PET-positive, who have had at least one prior systemic treatment and meet performance-status and organ-function requirements are eligible.
Not a fit: Patients whose tumors are not FAPi PET–avid, who have poor organ function or ECOG >1, or who cannot tolerate radioligand therapy are unlikely to benefit from this approach.
Why it matters
Potential benefit: If successful, the therapy could offer a new targeted option that shrinks tumors and prolongs disease control for patients with relapsed or treatment-resistant soft tissue sarcoma.
How similar studies have performed: Alpha-emitter radioligand therapies (including actinium agents) have shown promising activity in other cancers such as prostate cancer, but FAPi-targeted actinium therapy in soft tissue sarcoma is novel and early in development.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
* 18 years of age or older.
* History of relapse and refractory soft tissue sarcoma.
1. Histological confirmation of sarcoma at any point since diagnosis
2. 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:
1. Neutrophil count ≥ 1200 µL without granulocyte colony stimulating factor
2. Platelet count ≥ 100,000 µL
3. Hemoglobin ≥ 8 g/dL
4. Total bilirubin level ≤ 1.5 × upper limit of normal (ULN).
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
6. 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.
8\. The patient or the patient's legal representative must be willing and able to provide written informed consent.
Exclusion Criteria:
* History of whole pelvic irradiation.
* History of radioligand therapy.
* Treatment within 14 days prior to first administration with:
1. Palliative surgery or external beam radiation.
2. Approved anticancer therapy including chemotherapy or immunotherapy.
3. Any investigational therapy.
4. 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.
* Currently pregnant or lactating.
* Known allergy to any of the study drugs or their excipients.
* Inability or unwillingness to comply with any of the required imaging studies or study assessments.
Where this trial is running
Los Angeles, California and 5 other locations
- UCLA — Los Angeles, California, United States (Recruiting)
- Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
- Memorial Sloane Kettering Cancer Center — New York, New York, United States (Recruiting)
- Case Western — Cleveland, Ohio, United States (Recruiting)
- MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
- Princess Margaret Cancer Centre — Toronto, Ontario, Canada (Not_yet_recruiting)
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.