Xaluritamig for relapsed or refractory Ewing sarcoma in adults, adolescents, and children

A Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Xaluritamig in Adult, Adolescent and Pediatric Participants With Relapsed or Refractory Ewing Sarcoma

This trial will test xaluritamig in adults, adolescents, and children with relapsed or refractory Ewing sarcoma to find a recommended dose for expansion and check safety and tolerability.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 2 Years and up
• Sex: All
• Sponsor: Amgen (Industry-sponsored)
• Drugs / interventions: CAR-T, Chimeric Antigen Receptor, chemotherapy, prednisone
• Locations: 6 sites (Los Angeles, California and 5 other locations)
• Trial ID: NCT07297979 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional trial enrolls adults, adolescents, and children with relapsed or refractory Ewing sarcoma who have an EWSR1‑ETS translocation. It includes a dose confirmation part to identify the recommended dose for expansion and closely monitors safety and tolerability. Eligible participants must have prior chemotherapy (including an anthracycline and an alkylating agent), measurable or evaluable disease per RECIST v1.1, and adequate organ function and performance status. The investigational agent administered is xaluritamig (AMG 509) at participating U.S. cancer centers.

Who should consider this trial

Good fit: Ideal candidates are patients of any age with histologically confirmed Ewing sarcoma carrying an EWSR1‑ETS translocation, relapsed or refractory after at least one line of chemotherapy (including an anthracycline and an alkylating agent), with measurable or evaluable disease per RECIST and adequate organ function and performance status.

Not a fit: Patients without an EWSR1 translocation, those who are treatment‑naïve, have poor performance status, inadequate organ function, or cannot meet RECIST disease requirements are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, xaluritamig could provide a new targeted treatment option that controls disease or delays progression for patients with relapsed or refractory Ewing sarcoma.

How similar studies have performed: This is an early-phase application of xaluritamig in Ewing sarcoma; similar targeted approaches for EWSR1 fusion–driven tumors remain experimental with limited clinical success to date.

Eligibility criteria

Inclusion Criteria:

1. Part 1: evaluable disease as defined by RECIST v1.1, as determined by the site investigator.

   Part 2: measurable disease as defined by RECIST v1.1, as determined by the site investigator.
2. Histologically or cytologically confirmed EWS with molecular evidence of an EWSR1 translocation with an E26 transformation-specific (ETS) family gene, eg, FLI1, ETS-related gene \[ERG\]) via next generation sequencing (based on local testing).
3. Relapsed or refractory EWS following at least 1 line of chemotherapy (including treatment with an anthracycline and at least 1 alkylating agent).
4. Performance status:

   1. Karnofsky ≥ 70% for participants ≥ 16 years of age.
   2. Lansky ≥ 70% for participants \< 16 years of age.
5. Adequate organ function, defined as follows:

   a. Hematological function: i. Absolute neutrophil count ≥ 1.0 x 109/L, provided that:
   * the participant has not received short-acting growth factor support within 7 days before screening assessment, and
   * the participant has not received long-acting growth factor support within 14 days before screening assessment.

   ii. Platelet count ≥ 75 x 109/L, provided that:
   * the participant has not received a platelet transfusion within 7 days before screening assessment, and
   * the participant has not received a platelet stimulating agent within 14 days before screening assessment.

     b. Renal function: i. Estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation ≥ 30 mL/min/1.73 m\^2 for participants ≥ 18 years of age.

   ii. estimated glomerular filtration rate based on Schwartz (2009) calculation ≥ 30 mL/min/1.73 m\^2 for participants \< 18 years of age.

   c. Hepatic function: i. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) (or ≤ 5 x ULN for participants with liver metastases).

   ii. Total bilirubin (TBL) ≤ 1.5 x ULN (unless related to Gilbert's or Meulengracht disease).

   d. Pulmonary function: i. Baseline oxygen saturation \> 92% in room air at rest and no oxygen supplementation.

   e. Cardiac function: i. Left ventricular ejection fraction ≥ 50%. If left ventricular ejection fraction cannot be measured, then left ventricular fractional shortening ≥ 28%.
6. Participants of childbearing potential must use protocol-specified contraception to prevent pregnancy during treatment and for an additional 6 months after the last dose of xaluritamig.

Exclusion Criteria:

1. Untreated central nervous system (CNS) metastases or leptomeningeal disease. Participants with a history of treated CNS metastases are eligible if there is radiographic evidence of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study.
2. History of other malignancy within the past 2 years, except for malignancy treated with curative intent with low risk for recurrence (approximately \< 10%) and with no known active disease present for \>1 year before enrollment.
3. Active autoimmune disease that has required systemic treatment (except physiologic adrenal hormone replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study. Participants with Type 1 diabetes, vitiligo, psoriasis, hypo- or hyper-thyroid disease not requiring immunosuppressive treatment are permitted.
4. Participants who received anti-cancer therapy administered within the following minimum washout periods prior to first dose of xaluritamig:

   1. Cytotoxic chemotherapy: 21 days.
   2. Small molecules including tyrosine kinase inhibitors: 7 days or 5 half-lives, whichever is shorter.
   3. Monoclonal antibodies, immune checkpoint inhibitors, bispecific antibodies and other biologic agents: 28 days or 5 half-lives, whichever is shorter.
   4. Cellular therapies including Chimeric Antigen Receptor T-cell therapy (CAR-T), adoptive T-cell therapy: 56 days.
   5. Radiotherapy: 14 days for focal therapy, 28 days for large field therapy or involving \> 30% of the bone marrow.
   6. Stem cell transplant: 12 weeks for autologous, 6 months for allogeneic, with no active graft-versus-host disease.
   7. Any other therapy or investigational agent: 28 days or 5 half-lives, whichever is longer.
5. Requirement for chronic systemic corticosteroid therapy (prednisone dose \> 10 mg/day \[\> 0.25 mg/kg/day if \< 40 kg\] or equivalent) or any other immunosuppressive therapies (including anti-tumour necrosis factor α (TNFα) therapies) unless stopped (with adequate tapering) within 28 days before first dose of xaluritamig.
6. Currently pregnant (confirmed with positive pregnancy test) or breastfeeding or planning to become pregnant, donate eggs, or breastfeed while on trial until an additional 6 months after the last dose of trial intervention.
7. Unwilling to abstain from donating sperm during treatment and for an additional 6 months after the last dose of xaluritamig.

Where this trial is running

Los Angeles, California and 5 other locations

• Cedars Sinai Medical Center — Los Angeles, California, United States (Recruiting)
• University of California Los Angeles — Los Angeles, California, United States (Recruiting)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• Chris OBrien Lifehouse — Camperdown, New South Wales, Australia (Recruiting)
• Peter MacCallum Cancer Centre — Melbourne, Victoria, Australia (Recruiting)
• Perth Childrens Hospital — Nedlands, Western Australia, Australia (Recruiting)

Study contacts

• Study coordinator: Amgen Call Center

Conditions Ewing Sarcoma; Relapsed or refractory Ewing sarcoma; EWS; Xaluritamig; AMG 509