Phase I study of the

BACKGROUND

Lutathera is a

METHODS

Patients with relapsed/refractory extensive-stage SCLC (ES-SCLC), 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 a standard 3+3 design, assessing two dose levels (dose level 1: lutathera 3.7 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks; dose level 2: lutathera 7.4 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks).

RESULTS

Nine patients were enrolled (six ES-SCLC, two pulmonary atypical carcinoid, one high-grade pulmonary neuroendocrine carcinoma). No dose-limiting toxicities (DLTs) were observed at dose level 1. At dose level 2, one patient with refractory ES-SCLC developed a DLT (grade 3 rash). The most common treatment-related adverse events (TRAEs) were lymphopenia (n=7), thrombocytopenia (n=4), anemia (n=3), and nausea (n=3). The most common grade 3 TRAE was lymphopenia (n=4). Among the seven patients with measurable disease, one patient with ES-SCLC had a partial response. Two patients with pulmonary atypical carcinoid had stable disease lasting 6 months. The RP2D was dose level 2.

CONCLUSIONS

Lutathera plus nivolumab was well tolerated and showed signs of antitumor activity. This combination warrants further exploration.

TRIAL REGISTRATION NUMBER

NCT03325816.

Informations de copyright

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: CK has received research grants (to institution) from AstraZeneca, BMS, Novartis, Regeneron, Tesaro, Karyopharm, Debiopharm, and Altor Bioscience, and has served on the advisory board of Novartis. SVL has received research grants (to institution) from Alkermes, AstraZeneca, Bayer, Blueprint, Bristol-Myers Squibb, Corvus, Genentech, Ignyta, Lilly, Lycera, Merck, Merus, Molecular Partners, Pfizer, Rain Therapeutics, RAPT, Spectrum, and Turning Point Therapeutics. He has served on the advisory board of AstraZeneca, Bristol-Myers Squibb, Catalyst, Celgene, G1 Therapeutics, Genentech/Roche, Guardant Health, Ignyta, Janssen, Lilly, LOXO, PharmaMar, Regeneron, and Takeda. DSS is an employee of AstraZeneca and has stock options with AstraZeneca starting July 29, 2019. DSS was on the speaker’s bureau of AstraZeneca, Genentech, and Takeda Oncology, and was on the advisory board of AstraZeneca. GE is on the speaker’s bureau of Advanced Accelerator Applications. The other authors declare no potential conflicts of interest.