Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma

NCT05734066 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: JZP712-101
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 15

Brief Summary

This study is conducted in two phases. The phase 1 portion of the study evaluates the safety, tolerability, pharmacokinetics (PK), recommended phase 2 dose (RP2D), and effectiveness of lurbinectedin monotherapy in pediatric participants with previously treated solid tumors. This is followed by the phase 2 portion, to further assess the effectiveness and safety in pediatric and young adult participants with recurrent/refractory Ewing sarcoma.

Conditions

Refractory Ewing Sarcoma; Relapsed Ewing Sarcoma; Ewing Sarcoma

Keywords

Solid Tumors; lurbinectedin; ewing's sarcoma; soft tissue sarcoma; sarcomas

Outcome Measures

Primary Outcomes (5)

• Phase 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs)

  From the first dose through end of Cycle 1 (21 days).

• Phase 1: Number of Participants Experiencing Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs)

  Post-baseline (Day 1) up to approximately 31 months.

• Phase 1: Number of Participants With Dose Modifications

  Post-baseline (Day 1) up to approximately 31 months.

• Phase 1: Number of Participants Who Discontinued Study Intervention Due to TEAEs

  Post-baseline (Day 1) up to approximately 31 months.

• Phase 2: Objective Response Rate (ORR) Based on Investigator Assessment (IA)

  Day -28 up to a total of 13 months postdose.

Secondary Outcomes (38)

• Phase 1: Plasma Concentration of Lurbinectedin

  Day 1: Predose up to approximately 168 hours postdose; Days 16, 31, 46: Predose up to approximately 5 minutes postdose.

• Phase 1: Objective Response Rate (ORR) Based on Investigator Assessment (IA)

  Day -28 up to a total of 31 months postdose.

• Phase 1: Progression-Free Survival (PFS) Based on Investigator Assessment (IA)

  Day -28 up to a total of 31 months postdose.

• Phase 1: Duration of Response (DOR) in Participants with Confirmed Complete Response (CR) or Partial Response (PR)

  Day -28 up to a total of 31 months postdose.

• Phase 1: Disease Control Rate (DCR)

  Day -28 up to a total of 31 months postdose.

Study Arms (3)

Phase 1 Part 1: Dose Selection

EXPERIMENTAL

Pediatric participants ≥ 2 to \< 18 years of age with previously treated solid tumors of any histology at 5 dose levels to determine the RP2D, followed by a safety expansion cohort. Participants aged ≥ 6 to \< 18 years will be enrolled at the starting dose of 3.2 mg/m\^2 lurbinectedin. If, after review, the starting dose of 3.2 mg/m\^2 lurbinectedin Q3W is deemed safe in participants aged ≥ 6 to \< 18 years, participants aged ≥ 2 to \< 6 years may enroll and start at the dose as determined by the DMC. After this, the study opens to all participants (aged ≥ 2 to \< 18 years) for all dose levels. Upon completion of the cohort at all dose levels, participants may be eligible to enroll in a safety expansion cohort.

Drug: Lurbinectedin

Phase 1 Part 2: RP2D

EXPERIMENTAL

Participants aged ≥ 2 to ≤ 30 years with recurrent/refractory Ewing sarcoma at the RP2D to assess safety and efficacy signals.

Drug: Lurbinectedin

Phase 2

EXPERIMENTAL

If a signal of efficacy is observed in Phase 1 Part 2, additional participants aged ≥ 2 to ≤ 30 years with recurrent/refractory Ewing sarcoma will be enrolled. Phase 2 will further assess the safety and efficacy of lurbinectedin monotherapy.

Drug: Lurbinectedin

Interventions

Lurbinectedin DRUG

Administered as intravenous (IV) infusion once every 3 weeks (Q3W)

Also known as: JZP712

Phase 1 Part 1: Dose Selection; Phase 1 Part 2: RP2D; Phase 2

Eligibility Criteria

• Age: 2 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age
• Participant must meet the following age requirements at the time the informed consent form (ICF) (and assent form, if applicable) is signed:
• Phase 1 Part 1: participants must be ≥ 2 to \< 18 years of age.
• Phase 1 Part 2: participants must be ≥ 2 to ≤ 30 years of age.
• Phase 2: participants must be ≥ 2 to ≤ 30 years of age.
• Type of Participant and Disease Characteristics
• Participant has a confirmed solid tumor
• The participant has a Lansky/Karnofsky performance status score of ≥ 50%.
• The participant has adequate liver function, evidenced by the following laboratory values:
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 × institutional ULN (with the exception of participants with Gilbert's syndrome who must have bilirubin \< 3 × institutional ULN).
• The participant has adequate bone marrow function, evidenced by the following:
• Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L (independent of growth factor support within 1 week of screening laboratories).
• Platelets ≥ 100 × 10\^9/L (without platelet transfusion within previous 7 days of screening laboratories).
• Hemoglobin ≥ 8 g/dL (note: may have been transfused).

You may not qualify if:

• Medical Conditions
• corrected QT interval (QTc) prolongation defined as a QTc ≥ 460 ms using the Bazett formula in age \< 18 years and QTc ≥ 470 ms using the Bazett formula in age ≥ 18 years.
• Known symptomatic Central nervous system (CNS) metastases requiring steroids. Participants with previously diagnosed CNS metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to enrollment, have discontinued high dose steroid treatment for these metastases for at least 2 weeks, and are neurologically stable (physiologic doses of steroids and short courses of steroids for other indications are acceptable).
• Persisting toxicity related to prior therapy; however, alopecia, sensory neuropathy, hypothyroidism, and rash Grade ≤ 2 are acceptable, and other Grade ≤ 2 adverse events (AEs) not constituting a safety risk based on the investigator's judgement are acceptable.
• An uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring antibiotic, antifungal, or antiviral therapy, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Any other major illness that, in the investigator's judgment, could substantially increase the risk associated with participation in this study.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high-risk for treatment complications.
• Prior/Concomitant Therapy
• Received prior treatment with lurbinectedin or trabectedin.
• Received prior treatment with any investigational product within 4 weeks of first infusion of study intervention. Observational studies are permitted.
• Received live or live attenuated vaccines within 4 weeks of the first dose of study treatment or plans to receive live vaccines during study participation. Administration of inactive vaccines or messenger ribonucleic acid (mRNA) vaccines (for example, inactivated influenza vaccines or COVID-19 vaccines) are allowed.
• Had major surgery ≤ 4 weeks or radiation therapy ≤ 2 weeks prior to enrollment unless fully recovered. Prior palliative radiotherapy is permitted, provided it was completed at least 2 weeks prior to participant enrollment.
• Received prior allogeneic bone marrow transplantation or solid organ transplant.
• Received chemotherapy ≤ 3 weeks prior to start of study intervention.
• Diagnostic Assessments

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead
• Jazz Pharmaceuticals Ireland Limited: collaborator

Study Sites (15)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

RECRUITING

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

RECRUITING

Children's Healthcare of Atlanta at Arthur M. Blank Hospital

Atlanta, Georgia, 30329, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21238, United States

RECRUITING

Corewell Health

Grand Rapids, Michigan, 49503, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Children's Health Dallas

Dallas, Texas, 75235, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

MeSH Terms

Conditions

Sarcoma, Ewing; Sarcoma

Interventions

PM 01183

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Jazz Study Director

  Jazz Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Clinical Trial Disclosure & Transparency

CONTACT

215-832-3750; ClinicalTrialDisclosure@JazzPharma.com

Study Design

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

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: February 17, 2023
• Study Start: May 23, 2023
• Primary Completion (Estimated): January 28, 2028
• Study Completion (Estimated): April 20, 2028
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (14); CA (1)