Phase Ib results from the phase Ib/II study of [ ¹⁷⁷ Lu]Lu-DOTA-TATE in combination with standard of care as a first-line treatment for pts with extensive-stage small cell lung cancer.

Abstract

3010 Background: Most pts with newly diagnosed extensive-stage small cell lung cancer (ES-SCLC) relapse after initial response to standard of care (SOC; platinum/etoposide + anti–programmed death-ligand 1 [PD-L1] therapy); novel combination strategies are needed. This Phase Ib/II study (NCT05142696) assessed [ 177 Lu]Lu-DOTA-TATE ( 177 Lu-DOTATATE) – a radioligand therapy with high affinity for somatostatin receptor 2 (SSTR2; a poor prognostic biomarker expressed in ~50% of SCLC tumors) – plus SOC. Here, we report Phase Ib data (cutoff 20 Nov 2025). Methods: Phase Ib was a dosage escalation study to determine the recommended dosage (RD) of 177 Lu-DOTATATE – alongside carboplatin AUC 5 + etoposide 100 mg/m 2 + anti–programmed cell death protein 1 (PD-1)/PD-L1 therapy (pre/post protocol amendment: tislelizumab 200 mg/atezolizumab 1200 mg, respectively) Q3W in the induction phase, and alongside anti–PD-1/PD-L1 therapy Q3W in the maintenance phase – in pts aged ≥18 y with newly diagnosed SSTR+ (by PET/CT) ES-SCLC. Cohorts of 3–6 pts were enrolled to increasing dosage levels (DLs) of 177 Lu-DOTATATE (backfill allowed to ≤10 pts); escalation was guided by dosage-limiting toxicity (DLT) rate (Bayesian Optimal Interval design) and other safety data. The primary endpoint was DLTs ( 177 Lu-DOTATATE–related adverse events within the 42-day DLT period). Results: Of 57 pts screened, 29 received treatment (median [range] age 62 [43–73] y; white 89.7%; male 44.8%; ECOG PS 0/1/2 37.9%/58.6%/3.4%; smoking history 100%; bone/brain/liver metastases 51.7%/13.8%/48.3%); 93.1% completed the induction phase (DL1 [3.7 GBq] 9/9; DL2a [5.55 GBq] 11/11; DL3a [7.4 GBq] 7/9). Median treatment duration between first/last dosage and cutoff was 14.2/9.4 months. For 177 Lu-DOTATATE, median (range) number of doses was 4.0 (1.0–7.0), duration was 4.1 (1–6) months, and cumulative activity was 22.7 (7.1–44.4) GBq. There were no DLTs in 17 evaluable pts. The table reports safety and preliminary efficacy data. Conclusions: The observed safety profile was consistent with expected toxicity; the RD for Phase II was 7.4 GBq. Clinical trial information: NCT05142696 . Safety and preliminary efficacy (N=29). AEs, % Any: all grades; Grade ≥3 100; 100 Treatment related 100 177 Lu-DOTATATE related 86.2* Serious 72.4 † Leading to discontinuation 24.1 ‡ Deaths due to AEs, n 2 § Confirmed best overall response, % 82.8 ¶ 6-month duration of response rate, % 28.5 (95% CI 11.8, 47.7) 6-month progression-free survival rate, % 36.1 (95% CI 19.0, 53.6) *Most commonly reported: thrombocytopenia (58.6) and anemia (44.8). † 66.7 DL1, 63.6 DL2a, 88.9 DL3a. ‡ 33.3 DL1, 27.3 DL2a, 11.1 DL3a. § DL1: cardiac failure, large intestinal hemorrhage (on-treatment death); not treatment related. ¶ 100 DL1, 90.9 DL2a, 55.6 DL3a. AE, adverse event; CI, confidence interval; DL, dosage level.