Activity of Lurbinectedin As Single Agent and in Combination in Patients with Advanced Small Cell Lung Cancer (SCLC)

Background: Lurbinectedin (PM01183, L) is a novel anticancer drug that inhibits activated transcription, induces DNA double-strand breaks generating apoptosis, and modulates tumor microenvironment. Relapsed SCLC still remains an unmet medical need. Methods: Antitumor activity and safety of Lurbinectedin in SCLC was reviewed in three clinical trials (n = 83 patients): two phase I in combination with doxorubicin (L+DOX; n = 48, two cohorts) or paclitaxel (L+TAX, n = 7), and a phase II single-agent basket trial (n = 28). Results: Median age was similar in these three studies. CNS was involved in 33% (L+DOX cohort A), 4% (L+DOX cohort B), 29% (L+TAX) and 0% of patients (L alone). Patients with sensitive disease were 52%, 64%, 71% and 71%, respectively. Activity was seen in the three studies (see Table). The most reported toxicity was hematological (G3-4 neutropenia/thrombocytopenia/febrile neutropenia: L+DOX Cohort A 96%/34%/34%; L+DOX Cohort B 89%/11%/14%; L+TAX 86%/0%/14%, and L alone 32%/4%/4%). Non-hematological toxicity was mainly G1-2 and included fatigue, nausea/vomiting, and transaminase increase.Table1529PDResponse Evaluable patientsLurbinectedin+DOX (q3wk)Lurbinectedin + TAX (q3wk)Lurbinectedin alone (q3wk)Cohort A L 3-5 mg FD D1 + DOX 50 mg/m2 D1 (n = 21)Cohort B L 2 mg/m2 D1 + DOX 40 mg/m2 D1 (n = 27)L 2.2 mg/m2 D1 + TAX 80 mg/m2 D1 & D8 (n = 7)L 3.2 mg/m2 D1 (n = 24)CR2 (10%)1 (4%)1 (14%)–PR12(57%)9 (33%)4 (57%)6 (25%)ORR14 (67%)10 (37%)5 (71%)6 (25%)SD3 (14%)9 (33%)–12 (50%)PD4 (19%)8 (30%)2 (29%)6 (25%)DCR17 (81%)19 (70%)5 (71%)18 (75%)DOR (mo)4.53.72.36.2+PFS (mo) Platinum-sensitive5.85.74.83.2+PFS (mo) CTFI >30d*4.65.3--D, day; DCR, disease control rate; DOR, duration of response; FD, flat dose; mo, months; q3wk, every 3 weeks; CTFI, chemotherapy free interval. Open table in a new tab D, day; DCR, disease control rate; DOR, duration of response; FD, flat dose; mo, months; q3wk, every 3 weeks; CTFI, chemotherapy free interval. Conclusions: Lurbinectedin shows activity as a single agent and in combination with other agents (DOX and TAX) in relapsed SCLC. Results were remarkable in terms of PFS, DCR and duration of response, especially in platinum-sensitive SCLC. Toxicity mainly consisted of transient myelosuppression, which was manageable with dose reductions and G-CSF use. A randomized Phase III with L+DOX is ongoing (ATLANTIS Study). Clinical trial identification: NCT01970540 Legal entity responsible for the study: PharmaMar SA Funding: PharmaMar SA Disclosure: M. Forster: Consulting or advisor or travel and accomodation in Lilly, Pfizer, BI, Novartis Merck, Astrazeneca. E. Calvo: Speakers' Bureau in Novartis and travel or accomodation expenses in Lilly, PsiOxus, Novartis. M.P. Lopez Criado: Relation with Lilly, Bristol, roche, and travel, accomodations with Bristol. J.A. Lopez-Vilarino de Ramos, X.E. Luepke-Estefan: Employee in PharmaMar. C. Kahatt, P. Lardelli, A. Soto-Matos: Employee and Stock in PharmaMar. All other authors have declared no conflicts of interest. Keywords: Lurbinectedin, SCLC, Phase I, Phase II