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The first part of this study is a standard 3+3 design to test the safety, tolerability and pharmacokinetic profile of lurbinectedin administered on a day 1, 4 schedule in patients with FET-fusion tumors.

Lurbinectedin will be administered on a Day 1, Day 4 schedule every 21 days. Doses will be determined in the phase 1 portion of the trial.

Lurbinectedin

Patrick Grohar, MD

Supriya Behl

Jenna Gedminas, MD

Chris Stamy

Christine Heske, MD

Mary Frances Wedekind Malone

Steven Dubois, MD

Alexandra Sala

Rashmi Chugh, MD

Cancer AnswerLine

The purpose of this study is to find out if a drug called lurbinectedin (the "study drug") is safe and effective at treating people with recurrent or relapsed solid tumors, including Ewing sarcoma.

In this study, the investigators will test the activity of lurbinectedin as a targeted therapy for FET (FUS, Ewing Sarcoma Breakpoint Region 1 (EWRS1), TATA-Box-Binding Protein Associated Factor 15 (TAF15)). Ewing sarcoma is driven by the Ewing Sarcoma-Friend Leukemia Integration 1 Transcription Factor (EWS-FLI1). Lurbinectedin has been shown to inhibit EWS-FLI1 and Ewing Sarcoma-Wilms' Tumor Gene 1 (EWS-WT1) in preclinical models. Therefore, the goal of this study is to see if Lurbinectedin can be used to inhibit EWS-FLI1, EWS-WT1, or other FET fusion proteins to drive tumor responses in patients.

The first part of this study is a standard 3+3 design to test the safety, tolerability and pharmacokinetic profile of lurbinectedin administered on a day 1, 4 schedule in patients with FET-fusion tumors. The second part of this study is a single-stage phase 2 design and will accrue 17 patients in parallel to the exploratory cohort after the Recommended Phase 2 Dose (RP2D) is determined.

Lurbinectedin in FET-Fused Tumors

Lurbinectedin in FET-Fusion Tumors (LIFFT)

First cycle (approximately 21 days) Dose Limiting Toxicities (DLTs) will be evaluated.

Adverse events to be reported during treatment and for at least 28 days after last dose.

Percentage of participants with complete response or partial response will be assessed approximately every 2 to 4 cycles through the end of treatment and up to at least 28 days after the last dose.

Event-free survival (EFS) is based on investigator assessment from baseline until Month 24.

Maximum observed plasma concentration (Cmax) will be used to assess Lurbinectedin Pharmacokinetics

Area under the concentration-time curve (AUC) will be used to assess Lurbinectedin Pharmacokinetics

Progression Free Survival (PFS) assessed from the first dose of study drug to earliest date of death or progressive disease.

Duration of Response (DoR) defined as time from date of first response (Complete Response or Partial Response) in responders to date of progression or death

Overall survival (OS) defined as the time from enrollment to date of death due to any cause.

Disease Control ate is defined as the percentage of patients who sustain a complete response, partial response, or stable disease over 5 years.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Lurbinectedin in FET-Fused Tumors	NCT05918640	Ewing Sarcoma Desmoplastic Sm... Pediatric Cance... Undifferentiate...	Lurbinectedin	10 Years -	Children's Hospital of Philadelphia
Lurbinectedin in FET-Fused Tumors	NCT05918640	Ewing Sarcoma Desmoplastic Sm... Pediatric Cance... Undifferentiate...	Lurbinectedin	10 Years -	Children's Hospital of Philadelphia
Lurbinectedin in FET-Fused Tumors	NCT05918640	Ewing Sarcoma Desmoplastic Sm... Pediatric Cance... Undifferentiate...	Lurbinectedin	10 Years -	Children's Hospital of Philadelphia

Spots Global Cancer Trial Database for ewing sarcoma breakpoint region 1 (ewrs1)