Lurbinectedine Mono-Agent Induces Responses in Second Line SCLC

The lurbinectedctine (PM1183) induced monotherapy responses in patients with relapsed small cell lung cancer (CPPC), meeting the primary endpoint of the overall response rate (ORR) in a single-arm phase II trial, according to an announcement by PharmaMar, the company developing lurbinectin.

The review by the investigators and the independent review committee fulfilled the main purpose, said the announcement; the specific results will be presented at a next medical conference.
Lurbinectin was the subject of a multicenter Phase II trial in a basket relating to the safety and effectiveness of the agent on various solid tumors at the end of the year. advanced state. The SCLC cohort included 105 patients from 9 countries in Europe and the United States.

Patients participating in the trial were treated with 3.2 mg / m² of lurbinectedin as an intravenous infusion of one hour every 3 weeks. Patients in the SCLC cohort must have previously undergone chemotherapeutic treatment and have an ECOG performance status of between 0 and 2. Previous treatment with trabectedin (Yondelis), central nervous system (CNS) impairment or an earlier or accepted malignancy. The primary endpoint was the ORR and the secondary endpoints included duration of response (DoR), progression free survival (PFS) and overall survival (OS).

Preliminary results of the test were presented at the ASCO annual meeting in 2018 with data from 68 patients. Of 61 evaluable patients, 24 received a response corresponding to a RRR of 39.3% (95% CI, 27.1% to 52.7%). Twenty-one additional patients achieved stable disease, 7 of whom had stable disease for at least 4 months, corresponding to a clinical benefit rate of 50.8% (95% CI, 37.7% to 63%), 9%). The overall rate of disease control was 73.8% (95% CI, 60.9% to 84.2%). The median was 6.2 months.

The median PFS was 4.1 months with lurbinectin (95% CI, 2.6-5.7). At 6 months, the PHC rate was 36.3% (95% CI, 23.2% to 49.5%). The median was 11.8 months (95% CI, 9.6-15.9). At 6 months, the ILI rate was 79.3% (95% CI, 67.6% to 91.0%) and 43.1% (95% CI, 22.5% to 63.7%). %) at 12 months.

Among the 66 CPL patients treated with lurbinectin, the most common grade 1/2 adverse events (AEs) were anemia (86.4%), the increase in ALT (58.5%), fatigue (51.5%), increase in AST (36.9%), neutropenia (31.8%), thrombocytopenia (31.8%) ), nausea (31.8%), increase in AP (24.6%), vomiting (18.2%), anorexia (16.7%), constipation (10.6%), increased bilirubin (9.6%), , 4%), and diarrhea (9.1%). Frequent grade 3/4 AEs included neutropenia, anemia, febrile neutropenia, ALT elevation, fatigue, and thrombocytopenia. Eleven patients required granulocyte colony stimulating factor.
Lurbinectedin is a selective inhibitor of transcription of trans-activated RNA polymerase II, which can be over-activated in certain tumors, such as CPPC. The agent, which is structurally related to the FDA-approved trabectedin, blocks transcription, which leads to a cascade of events promoting apoptosis.

In August 2018, the FDA awarded lurbinectedin an orphan drug designation for the treatment of patients with CPPC. In addition, in January 2019, the European agent received a favorable opinion of the designation of an orphan drug in Europe for the treatment of CPPC.

The agent is also being studied in the ATLANTIS Phase III Study (NCT02566993) for the treatment of patients with recurrent CPPC after failure of a platinum regimen. The combination of lurbinectedin and doxorubicin was compared in the study with cyclophosphamide, doxorubicin and vincristine or topotecan, with a primary endpoint of OS. According to PharmaMar, the trial ended in July 2018 and is awaiting results.

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