464 2SMALL (NCT04253145) phase I part: lurbinectidine (LUR) in combination with atezolizumab (ATZ) for second line extensive stage small cell lung cancer (ES-SCLC) patients (pts)
Santiago Ponce Aix, Alejandro Navarro, Reyes Bernabé, M.E. Olmedo, Trigo Jose Manuel, Jon Zugazagoitia Fraile, Luis Paz‐Ares
Abstract
<h3>Background</h3> Current front-line treatment for ES-SCLC includes chemotherapy plus a PD-L1 inhibitor. FDA has recently approved LUR for pretreated patients with SCLC. 2SMALL is a two-part phase 1/2 study assessing the safety, tolerability and efficacy of LUR in combination with ATZ as second line treatment for ES-SCLC. Here we report data from phase I part of the 2SMALL trial (data cut off 14-07-2021) <h3>Methods</h3> 2SMALL phase I was an open-label, single arm, dose exploration trial. Elegible patients had confirmed ES-SCLC, who progressed to first line platinum based treatment, ECOG performance status score 0-1 and adequate organ function; prior exposure to immunotherapy was not allowed. During dose finding phase pts received increasing doses of LUR (2.5 mg/m2 - 3.2 mg/m2) on day (D) 1 plus a fixed dose of ATZ (1200 mg) every 3 weeks following a standard 3+3 dose escalation design. Study endpoints included the definition of the safety profile and the recommended dose. Additional objectives included efficacy (ORR and PFS). <h3>Results</h3> 26 patients were treated, including male 14 pts (53,84%), with median age 60.6 years. Five pts received LUR 2.5 mg/m2 + ATZ 1200 mg, and 3 pts were evaluable without DLT. Out of the 21 pts who received LUR 3.2 mg/m2+ ATZ 1200 mg (6 pts with primary G-CSF), 5 pts (20.83%) developed DTLs: 2 pts G3 febrile neutropenia (9.52%) (1 pt with G4 thrombocytopenia), 2 pts G4 neutropenia lasting more than 72h (9.52%), 1 pt G4 thrombocytopenia (4.76%). Most frequent haematological adverse events ≥ grade 2 (21 pts) were neutropenia (42.86%), thrombocytopenia (28.57%), anaemia (19.05%); lymphopenia (4.76%) and febrile neutropenia (4.76%). The most common non-haematological TAEs ≥ grade 2 was asthenia 30,76%. No deaths treatment-related were reported. Objective responses were observed in 15 pts (ORR: 57.69%), including complete responses in 2 pts (7.69%), partial response in 13 pts (50%). 6 pts had stable disease (26.92%) and 3 pts progressive disease (11.54%). Disease control rate was 84.61%. With 8 pts censored for progression, median PFS was 4.93 months (range 3.37 - 7.67 months). <h3>Conclusions</h3> The combination of LUR plus ATZ was well tolerated, without unexpected toxicities. Transient haematological toxicity was dose limiting. The RD for further studies is LUR 3.2 mg/m2 on D1 + ATZ 1200 mg D1 with G-CSF. Preliminary anti-tumor activity is remarkable. 2SMALL trial part II is ongoing, and will provide further data regarding efficacy and safety of the regimen for second line SCLC. <h3>Trial Registration</h3> NCT04253145 <h3>References</h3> Subbiah V, Paz-Ares L, Besse B, et al. Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment. <i>Lung Cancer</i> 2020;<b>150</b>:90–96. Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. <i>Lancet Oncol</i> 2020; <b>21</b>(5):645–654. <h3>Ethics Approval</h3> Ethics committe Hospital Universitario 12 de Octubre