P1.12-04 A Phase I Study of the 177Lu-DOTA0-Tyr3-Octreotate in Combination with Nivolumab in Patients with Extensive-Stage Small Cell Lung Cancer

Abstract

Despite initial sensitivity to systemic treatment, most patients with extensive-stage small cell lung cancer (ES-SCLC) relapse. It has been shown that somatostatin receptors are expressed in SCLC. Lutathera is a 177Lutetium-labeled somatostatin analog approved for treatment of gastroenteropancreatic neuroendocrine tumors (NETs). Nivolumab, an anti-PD-1 antibody, in combination with lutathera may act synergistically to generate anti-tumor immunity. Here we report the final results of the phase I study of this combination in patients with ES-SCLC. This is a phase I/II trial of lutathera and nivolumab in patients with ES-SCLC (NCT03325816). For phase I, patients with either relapsed/refractory ES-SCLC or non-progressing ES-SCLC after first-line platinum-based chemotherapy, or advanced grade I-II pulmonary NETs were eligible. The primary objective was to determine the recommended phase 2 dose (RP2D). The phase I portion followed the standard 3+3 design, assessing two dose levels (dose level 1: Lutathera 3.7 GBq Q8W for 4 doses with nivolumab 240 mg Q2W; dose level 2: Lutathera 7.4 GBq Q8W for 4 doses with nivolumab 240 mg Q2W). The DLT period was defined as first 8 weeks after treatment initiation. Adverse events (AEs) were assessed per CTCAE 4.03. A total of 9 patients were enrolled. Three patients with ES-SCLC (2 relapsed ES-SCLC, 1 non-progressing ES-SCLC after first-line chemotherapy) were enrolled at dose level 1 and no DLTs were observed. At dose level 2, six patients (3 relapsed/refractory ES-SCLC, 2 metastatic atypical carcinoid, and 1 high-grade NET) were enrolled. One patient with refractory ES-SCLC developed a DLT (grade 3 rash). The most common treatment-related AEs (trAEs) were lymphopenia (n=7), thrombocytopenia (n=4), anemia (n=3), and nausea (n=3). 5 (55.5%) of 9 patients had grade 3 trAEs, but the most common grade 3 trAE was lymphopenia (n=4). Grade 3 anemia, thrombocytopenia, pneumonitis, and rash occurred in one patient each. No grade 4/5 trAEs were reported. Among 7 patients with measurable disease, 1 patient with non-progressing ES-SCLC had a confirmed partial response and 2 patients with metastatic atypical carcinoid had stable disease lasting 6 months. The RP2D was lutathera 7.4 GBq Q8W for 4 doses with nivolumab 240 mg Q2W. Evidence from this phase I study of lutathera and nivolumab suggests that the combination has a manageable safety profile and showed initial signs of antitumor activity. The safety and efficacy of the combination may be further explored in phase II as maintenance therapy in patients with ES-SCLC.