LINNOVATE: Lurbinectedin, Ipilimumab and Nivolumab for Soft Tissue Sarcoma — LINNOVATE  

Advanced Soft-tissue Sarcoma Clinical Trial

Official title: LINNOVATE: A Phase 1/2 Study of Safety/Efficacy Using LURBINECTEDIN, Combined With IPILIMUMAB, and NIVOLUMAB for Advanced Soft Tissue Sarcomas

Status Recruiting

Clinical Trial Summary

This is an open label, dose-seeking phase 1/2 study using escalating doses of LURBINECTEDIN administered intravenously with fixed doses of IPILIMUMAB and NIVOLUMAB administered intravenously.

Clinical Trial Description

This is an open label, dose-seeking phase 1/2 study using escalating doses of LURBINECTEDIN administered intravenously with fixed doses of IPILIMUMAB and NIVOLUMAB administered intravenously.

I. Dose Escalation Phase 1 of Study: The study will employ the standard "cohort of three" design (Storer, 1989). Three participants are treated at each of the 2 ascending dose levels. An additional 3 participants will be enrolled if a DLT is observed in one of the three initially-enrolled participants at each dose level. If no DLT occurs after the third participant in a dose level is on study for 6 weeks, enrollment will be opened for escalation to the next highest planned dose level. The DLT window is a total of 6 weeks. The MTD is defined as the highest safely tolerated dose of lurbinectedin, where not more than one participant experienced a DLT, with the next higher dose level having at least two participants who experienced DLT.

Participants in the dose escalation study may continue treatment at their designated dose levels until disease progression or unacceptable toxicity occurs or up to a maximum of one year of therapy (up to a maximum of 18 doses of LURBINECTEDIN, 26 doses of NIVOLUMAB, and 5 doses of IPILIMUMAB). No intra-participant dose escalation will take place.

Dose of IPILIMUMAB: 1 mg/kg IV over 30 min. q 12 weeks, beginning 2 weeks after the first dose of LURBINECTEDIN, until disease progression or unacceptable toxicity, up to a maximum of 5 doses

Dose of NIVOLUMAB: 3 mg/kg over 30 min. q 2 weeks, beginning 2 weeks after first dose of LURBINECTEDIN, until disease progression or unacceptable toxicity, up to a maximum of 26 doses

Dose of LURBINECTEDIN: Escalating doses of LURBINECTEDIN IV over 60 minutes q 3 weeks up to a maximum of 18 doses:

LURBINECTEDIN # Pts. Dose Level Dose,mg/m2 Max.Volume/24 hrs

Every 3 weeks 3-6 I 2.6 1000 ml Every 3 weeks 3-6 II 3.2 1000 ml

No dose-escalation will be performed until all the subjects have completed the DLT period of 6 weeks and evaluation of all clinical and laboratory data has been conducted. The phase 2 part of the study will not proceed until either the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been determined.

Participants who do not complete the DLT period for reasons other than study drug-related toxicity will be replaced in the same dose cohort. At the discretion of the principal investigator/sponsor, dose escalation may be stopped before an MTD is reached. In this case, the MAD may be chosen based on the standard dose of LURBINECTEDIN of 3.2 mg/m2. ;

Related Conditions & MeSH terms

• Advanced Soft-tissue Sarcoma
• Sarcoma

• NCT number: NCT05876715
• Study type: Interventional
• Source: Sarcoma Oncology Research Center, LLC
• Contact: Erlinda M Gordon, MD
• Phone: 310-552-9999
• Email: egordon@sarcomaoncology.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 7, 2023
• Completion date: September 30, 2026