Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): Primary results of the phase 3 IMforte trial.

8006 Background: Despite improved efficacy when adding 1L PD-(L)1 inhibitors to platinum-based chemotherapy for ES-SCLC, long-term survival remains limited. We report primary results from the global open-label, randomized, Phase 3 IMforte study (NCT05091567) of 1L maintenance tx with lurbi + atezo vs atezo in pts with ES-SCLC. Methods: Tx-naive pts with ES-SCLC received standard induction tx with atezo, carboplatin, and etoposide for four 21-day cycles (q3w). After induction, eligible pts without disease progression (PD) were randomized 1:1 to receive maintenance tx q3w with lurbi (3.2 mg/m 2 IV; with G-CSF prophylaxis) + atezo (1200 mg IV) or atezo alone until PD, unacceptable toxicity, or withdrawal. Pts were stratified by liver metastases at induction baseline (BL; yes/no), receipt of prophylactic cranial irradiation before randomization (yes/no), ECOG PS (0/1) and LDH (≤ULN/ > ULN) at maintenance BL. Crossover was not allowed. Primary endpoints were independent review facility (IRF)–assessed PFS per RECIST v1.1 and OS assessed from randomization into the maintenance phase. Results: Of 660 enrolled pts, 483 were randomized to receive lurbi + atezo (n = 242) or atezo (n = 241). BL characteristics were generally balanced between arms. With a median 15.0-mo follow-up (data cutoff: Jul 29, 2024), IRF-PFS was significantly improved with lurbi + atezo vs atezo (stratified HR, 0.54 [95% CI: 0.43, 0.67]; P < 0.0001; Table). A significant OS benefit was seen with lurbi + atezo vs atezo (stratified HR, 0.73 [95% CI: 0.57, 0.95]; P = 0.0174). Median maintenance tx duration was 4.1 mo with lurbi and 4.2 mo with atezo in the lurbi + atezo arm (n = 242) and 2.1 mo in the atezo arm (n = 240). In the lurbi + atezo and atezo arms, respectively, treatment-related AEs (TRAEs) occurred in 83.5% vs 40.0% of pts, G3/4 TRAEs in 25.6% vs 5.8% and G5 TRAEs in 0.8% (2 pts; sepsis, febrile neutropenia) vs 0.4% (1 pt; sepsis); AEs led to tx discontinuation in 6.2% vs 3.3%. Conclusions: IMforte met both primary endpoints of IRF-PFS and OS, demonstrating a clinically meaningful benefit with 1L maintenance tx with lurbi + atezo vs atezo in pts with ES-SCLC. Lurbi + atezo was generally well tolerated, with no new or unexpected safety signals. IMforte is the first global Phase 3 study to show PFS and OS improvement with 1L maintenance tx for ES-SCLC and supports maintenance lurbi + atezo as a new option for pts with this aggressive disease. Clinical trial information: NCT05091567 . Efficacy from randomization into maintenance phase Lurbi + atezo (n=242) Atezo(n=241) IRF-PFS Event, n (%) 174 (71.9) 202 (83.8) Median (95% CI), mo 5.4 (4.2, 5.8) 2.1 (1.6, 2.7) Stratified HR (95% CI) 0.54 (0.43, 0.67); P <0.0001 a ; α=0.001 b OS Event, n (%) 113 (46.7) 136 (56.4) Median (95% CI), mo 13.2 (11.9, 16.4) 10.6 (9.5, 12.2) Stratified HR (95% CI) 0.73 (0.57, 0.95); P =0.0174 a ; α=0.0313 b a Stratified log-rank. b 2-sided boundary.