2023 World Conference on Lung Cancer (Posters)-EP13.07. RYZ101 (Ac-225 DOTATATE) Opportunity Beyond GEP-NETs: Preclinical Efficacy in Small Cell Lung Cancer

EP13.07. RYZ101 (Ac-225 DOTATATE) Opportunity Beyond GEP-NETs: Preclinical Efficacy in Small Cell Lung Cancer - PDF(Abstract)

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A study presented at the World Conference on Lung Cancer 2023 explored the potential of RYZ101 (Ac-225 DOTATATE), a radiopharmaceutical therapy, for the treatment of small cell lung cancer (SCLC). The study aimed to provide preclinical support for the use of RYZ101 as a single-agent or in combination with carboplatin and etoposide for SCLC with somatostatin receptor (SSTR) expression.<br /><br />SCLC accounts for approximately 13% of lung cancers and lacks effective therapeutic options. However, immunohistochemistry analysis revealed that 50% of SCLC tumors express SSTR2, making them suitable targets for RYZ101.<br /><br />RYZ101 is composed of the alpha-emitting radioisotope actinium-225, the chemical chelator DOTA, and the somatostatin analogue octreotate (TATE). Preclinical studies demonstrated that RYZ101 had high binding affinity to human SSTR2 and efficient internalization. In biodistribution studies, RYZ101 showed similar performance to Lu-177 DOTATATE. In multiple SCLC xenograft models, RYZ101 significantly inhibited tumor growth and prolonged survival, especially in models with higher SSTR2 levels. The anti-tumor effect was further enhanced when RYZ101 was combined with carboplatin and etoposide.<br /><br />In summary, the preclinical data suggest that RYZ101 has potential as a treatment for SSTR-expressing SCLC. A Phase 1b trial of RYZ101 in combination with atezolizumab, carboplatin, and etoposide is currently underway in patients with SSTR ES-SCLC. This research highlights a potential opportunity for the use of RYZ101 beyond gastroenteropancreatic neuroendocrine tumors and demonstrates its efficacy in treating SSTR-positive SCLC.

Asset Subtitle

Ye Yuan

Meta Tag

Speaker Ye Yuan

Topic SCLC & Neuroendocrine Tumors: Relapse & Salvage Therapy

Keywords

World Conference on Lung Cancer 2023

RYZ101

Ac-225 DOTATATE

radiopharmaceutical therapy

small cell lung cancer

SCLC

carboplatin

etoposide

somatostatin receptor

SSTR expression