2024 World Conference on Lung Cancer (WCLC) - Posters-P1.13A.09 RYZ101 (225Ac-DOTATATE) + Carboplatin + Etoposide + Atezolizumab in Somatostatin Receptor Expressing Extensive-Stage Small-Cell Lung Cancer

P1.13A.09 RYZ101 (225Ac-DOTATATE) + Carboplatin + Etoposide + Atezolizumab in Somatostatin Receptor Expressing Extensive-Stage Small-Cell Lung Cancer

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The document outlines a Phase 1b clinical trial of RYZ101 (225Ac-DOTATATE) combined with standard chemoimmunotherapy (carboplatin, etoposide, and atezolizumab) for treating extensive-stage small-cell lung cancer (ES-SCLC) that expresses somatostatin receptor type 2 (SSTR2). RYZ101 is a novel radiopharmaceutical that utilizes alpha radiation to target cancer cells, potentially offering a more effective therapeutic approach with a higher proportion of double-strand DNA breaks compared to beta radiation.<br /><br />The trial involves dose escalation and expansion to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) while assessing safety, pharmacokinetics, and efficacy. Patients may receive up to six cycles of treatment, with dosage differing across study arms. Participants must have confirmed ES-SCLC, measurable SSTR2 sites from PET/CT scans, and meet several health criteria, including adequate bone marrow function and creatinine clearance.<br /><br />Preliminary results present safety data from the first cohort at a dose level of 6.5 MBq. Among the initial four patients, treatment-emergent adverse events (TEAEs) were observed in all individuals, but no dose-limiting toxicities (DLTs) occurred. Adverse events were generally low grade, with one unrelated Grade 4 neutropenia requiring intervention. Notably, no serious adverse events (SAEs) were linked to RYZ101.<br /><br />Pharmacokinetic data suggests a mean clearance of 1.72 mL/min/kg and a terminal half-life of 62.7 hours for RYZ101. The study's early analyses support the manageable safety profile of RYZ101 in combination therapy and encourage further dose escalation. These initial findings were shared at the IASLC World Conference on Lung Cancer, aiming to validate the implementation of RYZ101 for advanced SSTR2-positive SCLC cases.

Asset Subtitle

Sonam Puri

Meta Tag

Speaker Sonam Puri

Topic SCLC & Neuroendocrine Tumors

Keywords

Phase 1b clinical trial

RYZ101

225Ac-DOTATATE

chemoimmunotherapy

extensive-stage small-cell lung cancer

somatostatin receptor type 2

radiopharmaceutical

dose escalation

safety profile

pharmacokinetics