8094 Background: LUR has been approved in the US and elsewhere for treatment of adult pts with metastatic SCLC and disease progression on or after platinum-based chemotherapy. Preclinical studies found synergy for LUR with IRI (Galmarini C. Cancer Res 2013; 73: Abst 5499). The phase 1b/2 study PM1183-A-014-15 (NCT02611024) evaluated the LUR/IRI combination in pretreated pts with advanced solid tumors. The phase 1b part defined the recommended dose at LUR 2.0 mg/m 2 on Day (D)1 + IRI 75 mg/m 2 on D1,D8 every three weeks with primary G-CSF prophylaxis, and found promising results for the combination in SCLC pts after first-line therapy (Ponce Aix S. Ann Oncol 2019; 30: Abst 471P). Methods: Eligibility criteria for this cohort of the phase 2 part of this study included: confirmed SCLC, progression after one platinum-containing regimen, controlled brain metastases and ECOG PS ≤ 1. The primary endpoint was overall response rate (ORR). Results: 101 evaluable pts were enrolled. Baseline characteristics included: median age 63 (range, 45-77 y), 60.4% males, 76.2% ECOG PS 1, 28.7% CNS involvement, 39.6% bulky disease and 41.6% pretreated with immunotherapy. Chemotherapy-free interval (CTFI) was &lt;90 d in 51.4% of pts (26.7% had CTFI&lt;30 d. Median CTFI was 85 d (range, 0-323 d). Median number of cycles per pt was 6 (range, 1-34); 25.7% received &gt;10 cycles. Efficacy results by independent review committee are summarized in the table. Treatment-related adverse events (AEs) were observed in 99.0% of pts (grade ≥3 in 69.3%). Most relevant grade ≥3 events/abnormalities were neutropenia (52.5%), anemia (27.7%), diarrhea (19.8%), fatigue (18.8%), and febrile neutropenia (9.9%). Treatment-related SAEs occurred in 25.0% of pts and 5.0% discontinued due to treatment-related AEs. No treatment-related deaths occurred. Conclusions: The LUR/IRI combination showed promising antitumor activity and a manageable safety profile in these pts with poor prognosis, particularly those with CTFI&gt;30 d. These encouraging results reinforce the rationale for including this combination as an experimental arm in the ongoing pivotal phase 3 LAGOON trial (NCT05153239) in relapsed SCLC with CTFI&gt;30 d. Clinical trial information: NCT02611024 . [Table: see text]

Efficacy and safety of lurbinectedin (LUR) with irinotecan (IRI) in patients (Pts) with relapsed small cell lung cancer (SCLC): Results from a phase 2 expansion cohort.