Conference Coverage

Lurbinectedin shows activity against relapsed Ewing’s



CHICAGO – Single-agent lurbinectedin (PM1183, Zepsyre) showed “encouraging” activity against advanced Ewing’s Sarcoma in previously treated adults, results of a phase 2 study indicated.

Among 28 adults with Ewing’s sarcoma (ES) that had relapsed after up to two prior lines of therapy, treatment with lurbinectedin was associated with five partial responses and six cases of stable disease, reported Vivek Subbiah, MD, from the University of Texas MD Anderson Cancer Center in Houston and his colleagues.

“Treatment in combination with other agents is warranted in this patient population,” they wrote in a poster presented at the annual meeting of the American Society of Clinical Oncology.

Lurbinectedin’s mechanism of action is through blocking DNA transcription and inducing DNA double-strand breaks, which leads to programmed cell death.

“Moreover, in sarcomas associated with translocations, such as ES, in which the translocation produces a fusion protein that acts as a deregulated transcription factor, lurbinectedin might interfere with the binding of this protein to specific DNA promoters and thus with the synthesis of downstream proteins,” the investigators wrote.

This agent is being investigated against ES as part of a phase 2 basket trial, which is testing the drug against a variety of malignancies. The ES cohort in this study included 15 adults who had received up to two prior chemotherapy regimens. The trial rules called for recruitment of a minimum of 10 more patients if at least one of the first 15 had a confirmed response. There were two responses among the 15 patients, leading to an expansion cohort with 13 patients, for a total of 28 in the current analysis.

The median patient age was 33 years (range, 18-74 years). The majority of patients had good performance status, with Eastern Cooperative Oncology Group scores of 0 (11 patients) or 1 (15 patients); one patient had an ECOG PS score of 2, and one had unknown status.

All but one patient had received a minimum of two prior lines of therapy.

The patients were treated with lurbinectedin 3.2 mg/m2 in a 1-hour infusion on day 1 of every 21-day cycle, with the longest duration of therapy out to 14 cycles.

Among 25 evaluable patients, eight had tumor shrinkage, ranging from less than 5% (two patients) to more than 45% (four patients).

Median progression-free survival (PFS) was 2.7 months. The 4-month PFS rate was 42.9%, and the 6-month rates was 21.4%.

A total of 11 patients had some clinical benefit, including five partial responses and six cases of stable disease.

Grade 3 or 4 treatment-related adverse events included febrile neutropenia (two events grade 3 and two grade 4), anemia (five events, all grade 3), neutropenia (five grade 3 and 10 grade 4), thrombocytopenia (four grade 3 events), and elevated alanine aminotransferase levels (two grade 3 events).

Myelosuppression was transient and manageable with granulocyte colony-stimulating factor, the investigators said.

The study was supported by PharmaMar. Dr. Subbiah disclosed travel, accommodations, and/or expenses from the company and from Bayer; a consulting or advisory role with MedImmune; and institutional research funding from PharmaMar and multiple other companies.

SOURCE: Subbiah V et al. ASCO 2018, Abstract 11519.