Evaluation of Xaluritamig in Adults, Adolescents and Children With Relapsed or Refractory Ewing Sarcoma (EWS)

NCT ID: NCT07297979

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-16
• Study Completion Date: 2029-07-12

Brief Summary

The main objectives of this trial are to determine the recommended dose for expansion of xaluritamig (dose confirmation part only) and to determine the safety and tolerability of xaluritamig in adult, adolescent and pediatric participants with relapsed or refractory EWS.

Conditions

Ewing Sarcoma

Keywords

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Part 1 (Dose Confirmation)

Part 1 will begin with a pre-specified xaluritamig target dose and frequency. Multiple dose levels and/or alternative dose regimens may be explored in parallel to determine 1 or more recommended doses for expansion, which is/are considered safe, based on emerging data.

Group Type: EXPERIMENTAL

Xaluritamig

Intervention Type: DRUG

Participants will receive xaluritamig via short-term intravenous (IV) infusion.

Part 2 (Dose Expansion)

Participants will be treated in Part 2 after the recommended doses for expansion for xaluritamig are determined in Part 1 to further characterize preliminary antitumor activity and safety.

Group Type: EXPERIMENTAL

Xaluritamig

Intervention Type: DRUG

Participants will receive xaluritamig via short-term intravenous (IV) infusion.

Interventions

Xaluritamig

Participants will receive xaluritamig via short-term intravenous (IV) infusion.

Intervention Type: DRUG

Other Intervention Names

AMG 509

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.

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Central Contacts

Amgen Call Center

Role: CONTACT

Phone: 866-572-6436

Email: medinfo@amgen.com

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20200034

Identifier Type: -

Identifier Source: org_study_id