KEY TAKEAWAYS
- The phase Ib/II trial aimed to determine the optimal dosing of lurbi and dox for treating metastatic leiomyosarcoma.
- The study enrolled 50 pts with LMS and took PFS as the primary endpoint.
- The combination of Lurbi and Dox was well-tolerated and has shown efficacy in STS. The phase 2 study is currently enrolling pts.
Doxorubicin (Dox) and gemcitabine are standard treatments for metastatic leiomyosarcoma (LMS) but are ineffective. Lurbinectedin (Lurbi) is a new drug that binds to DNA and induces apoptosis. A pilot study showed that lurbinectedin plus doxorubicin is well-tolerated and effective in LMS.
Researchers aimed to determine the optimal dosing of lurbi and dox for treating metastatic leiomyosarcoma.
Patients (pts) over 18 years old with advanced/metastatic non-GIST soft tissue sarcoma (STS), ineligible for surgery, without prior anthracycline/Lurbi/trabectedin, ECOG PS < 3, RECIST 1.1 measurable, and normal organs were included. Phase 1b used a 3+3 design. Lurbi (3.2 mg/m² on day 1) and two Doxorubicin levels (DL1: 25 mg/m² on day 1; DL2: 25 mg/m² on days 1+8) were tested with GCSF support. DL1 became RP2D. Phase 2, from Aug 2022, enrolled 50 LMS patients, 1:1 randomization (stratified by uterine LMS [uLMS] vs. other LMS), focusing on progression-free survival(PFS). Dox progressors could shift to Lurbi monotherapy.
Phase 1b had 10 pts with histologies of 5 LMS (4 uLMS) and 1 each of myxofibrosarcoma (myxFS), undifferentiated pleomorphic sarcoma (UPS), dedifferentiated liposarcoma (DDLPS), endometrial stromal sarcoma (ESS), and solitary fibrous tumor (SFT). Median follow-up was 344 days; 5/10 patients were still on treatment, and median PFS was 357 days (95% CI 175-ND). Around 6 pts had a partial response (PR; 5 confirmed), 3 stable diseases (SD), and 1 progressive disease (PD). The median time to PR was 81 days (range 46-207). Responders had over 132 days of the response, with 3 ongoing treatments. Typical Dox/Lurbi adverse events (AEs) were seen.
The study found that Lurbi+Dox was well-tolerated and effective in STS, with 6/10 pts achieving PR and 9/10 pts on treatment for >120d. The phase 2 study is ongoing.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.11507
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT05099666
Gregory Michael Cote, Candace L. Haddox, Edwin Choy, Priscilla Merriam, Emanuele Mazzola, Andrew J. Wagner, Brittany L. Siontis, Steven Attia, Mahesh Seetharam, George D. Demetri, and Suzanne George. DOI: 10.1200/JCO.2023.41.16_suppl.11507 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 11507-11507.
