March 27, 2017 // By Dave Levitan .
A novel compound known as PM01183 (lurbinectedin) showed promising activity in a two-stage phase II trial of women with platinum-resistant/refractory ovarian cancer.
PM01183 is a synthetic tetrahydroisoquinoline that selectively inhibits active transcription, inducing DNA breaks and apoptosis and affecting the inflammatory microenvironment. “Strong preclinical antitumor activity was observed in cisplatin-resistant epithelial ovarian cancer models,” wrote study authors led by Andrés Poveda, MD, of the Instituto Valenciano de Oncología in Valencia, Spain.
This study included two phases: in the first exploratory stage, 22 patients with platinum-resistant/refractory ovarian cancer were treated with single-agent PM01183 at 7.0 mg every 3 weeks. The second stage was randomized, with 30 patients receiving PM01183 and 29 control patients receiving topotecan (15 crossed over to receive PM01183). The results were published in Annals of Oncology.
Among the 52 total patients treated with PM01183, there were 12 confirmed responses, including 1 complete response and 11 partial responses, for an objective response rate of 23%. The median duration of response was 4.6 months, and 23% of the responses lasted at least 6 months. The median progression-free survival (PFS) in these patients was 4.0 months, and the median overall survival (OS) was 10.6 months.
Most of the responders (75%) had an ECOG score of 0 at baseline, and most were younger than 65 years of age. Ten of the 12 (83%) had platinum-resistant disease, and two had a BRCA mutation. The objective response rate was 30% among the 33 patients with platinum-resistant disease, and the median PFS was 5.0 months.
There were no responses seen among the 29 topotecan patients. Just among the randomized patients, the median PFS was 3.9 months with PM01183 and 2.0 months with topotecan (P = .0067); OS was no different, at 9.7 months with the study drug and 8.5 months with topotecan (P = .2871).
Myelosuppression was the most common adverse event seen with PM01183. Grade 3/4 neutropenia occurred in 85% of PM01183 patients (64% with grade 4), and grade 3/4 thrombocytopenia occurred in 33%. Fatigue of any grade occurred in 77% of PM01183-treated patients, and was the most common nonhematologic toxicity. There was 1 patient with grade 3 rhabdomyolysis that was related to treatment. No treatment-related deaths occurred in the study.
“PM01183 is an active drug in platinum-resistant/refractory ovarian cancer and warrants further clinical development, particularly in platinum-resistant disease, where its activity was remarkable,” the authors concluded. The drug is now being tested in the phase III CORAIL trial, which includes patients with platinum-resistant ovarian cancer.