1739P - Linnovate: A phase I/II study of safety/efficacy using lurbinectedin combined with ipilimumab and nivolumab for advanced soft tissue sarcoma (NCT05876715) - Interim analysis of phase I part

Background

Immune checkpoint inhibitors are most effective when given as first line therapy, together with a tumoricidal agent, such as lurbinectedin, whose plausible mechanism of action is not only to destroy cancer cells but also to destroy growth promoting factors in the tumor microenvironment. Lurbinectedin is FDA approved as monotherapy at a dose of 3.2 mg/m2 IV q 3 weeks for adults with metastatic SCLC with disease progression on or after platinum-based chemotherapy.

Methods

Objectives: (1) Assess MTD of lurbinectedin in combination with Ipilimumab (Ipi) and Nivolumab (Nivo); (2): Evaluate PFS, OS, incidence and severity of adverse events; (3) Correlate response with ctDNA using Signatera. This is a dose-seeking phase I/II study. The phase I part employs standard “cohort of three” design with a DLT window of 3 weeks. Eligible patients are 18 years of age or older, previously treated in phase I and previously untreated in phase II with confirmed diagnosis of advanced STS, adequate hematologic and organ function, and no history of autoimmune disorder. Treatment Schedule: Ipi 1 mg/kg IV q 12 weeks; Nivo 3 mg/kg IV q 2 weeks; escalating doses of lurbinectedin from 2.6 mg/m2 to 3.2 mg/m2 IV q 3 weeks. Phase II: 28-34 participants will receive lurbinectedin at the MTD/MAD with fixed doses of Ipi and Nivo. Participants may continue treatment until significant disease progression or unacceptable toxicity occurs.

Results

Histologic subtypes: LMS, Uterine (n=1), Ewing (n=1), UPS (n=1), endometrial stromal sarcoma (n=1), synovial sarcoma (n=2). Median number of chemo/targeted therapy regimens: 3 (range 2-5). Six patients in phase I have completed one treatment cycle with no dose limiting toxicity. The MTD/MAD was determined to be 3.2 mg/m2. Overall response at 6 weeks: SD (100%). Median PFS and median OS not yet reached; No SAEs reported during DLT period.

Conclusions

Taken together, the data shows that (1) lurbinectedin combined with ipilimumab and nivolumab is a safe regimen with a MTD of 3.2 mg/m2 for lurbinectedin and (2) there were no serious treatment related adverse events reported. The phase II part of the study is currently open for previously untreated patient enrollment.

Clinical trial identification

NCT05876715.

Editorial acknowledgement

Legal entity responsible for the study

Sarcoma Oncology Research Center.

Funding

Jazz Pharmaceuticals.

Disclosure

All authors have declared no conflicts of interest.