LuSato-1: Phase I study of ¹⁷⁷ Lu-SSO110 with ⁶⁸ Ga-SSO120 companion imaging in patients with extensive stage small cell lung cancer (ES-SCLC) on maintenance treatment with immune checkpoint inhibition (ICI).

8011 Background: Outcomes for pts with ES-SCLC remains suboptimal despite the addition of ICIs to platinum-based chemotherapy. Somatostatin receptor 2 (SSTR2) is expressed in the majority of SCLC lesions. SSTR2 targeted radiopharmaceutical therapy (RPT) has proven safe and effective when used in other neuroendocrine tumors. The multicentre, open-label, phase I LuSato-1 (ACTRN12623000185662) study investigated the use of 177 Lu-satoreotide Tetraxetan ( 177 Lu-SSO110) with 68 Ga-Satoreotide Trizoxetan ( 68 Ga-SSO120) companion imaging in pts with ES-SCLC, who are on 1L maintenance ICIs. Methods: Adult pts with ES-SCLC received 1L induction therapy with carboplatin, etoposide and atezolizumab for 4 cycles. Following induction, eligible pts without PD were enrolled and received up to 4 doses of 177 Lu-SSO110 in 6 to 9 week intervals, with up to 3 additional treatments per investigator choice. Activities were escalated from 3.7GBq to 5.2GBq, following a BOIN design with a target DLT rate of 0.30. The primary objective was to investigate the safety and tolerability of 177 Lu-SSO110 with 68 Ga-SSO120 companion imaging in pts on maintenance ICI, with secondary objective of anti-tumor activity of the combination. Concordance between 68 Ga-SSO120 PET/CT and contrast-enhanced CT was an exploratory endpoint. Results: Of the 35 screened pts, 20 were deemed eligible (median age 65.5 years (range 47-83), 55% female, 25% brain mets). With a median 11.1 month follow up (data cut off: 08/12/25), the TEAE rate associated with 177 Lu-SSO110 was 0% at 3.7GBq (dose level 1), 71.4% at 4.5GBq (dose level 2), and 83.3% at 5.2GBq (dose level 3). The grade 3/4 TEAE rate associated with 177 Lu-SSO110 was 0% (dose level 1), 57.1% (dose level 2), and 41.7% (dose level 3). Grade 2 to 4 thrombocytopenia rate related to 177 Lu-SSO110 was 45%. Grade 3/4 irAEs related to ICI was 20%. There was 10% pneumonitis rate attributed to ICI. The treatment interruption rate was 50% and treatment discontinuation rate was 10% (2 attributed to 177 Lu-SSO110 associated thrombocytopenia). From the start of C1 induction chemoICI, the ORR was 85%, including 1 CR. From the start of maintenance ICI, median PFS was 3.7 months and median OS was 8 months. Conclusions: Addition of SSTR2 targeted RPT to maintenance ICI was well tolerated and demonstrated clinically meaningful anti-tumor activity. This supports further investigation of SSTR2-targeted RPT in combination with ICI in patients with ES-SCLC. Clinical trial information: ACTRN12623000185662. ORR, PFS and OS. Efficacy ES-SCLC patients N=20 Best response rates (from C1 induction) CR 1 (5%) PR 16 (80%) SD 3 (15%) ORR (from C1 induction) 17 (85%) Median PFS (months) (from C1 maintenance) 3.7 months Median OS (months) (from C1 maintenance) 8 months