RYZ101 + Carboplatin + Etoposide + Atezolizumab in Somatostatin Receptor Expressing Extensive-Stage Small-Cell Lung Cancer

Document Type

Conference Proceeding

Publication Date


Publication Title

Journal of Thoracic Oncology


Introduction: RYZ101 (225Ac-DOTATATE) is a first-in-class, highly potent alpha-emitting radiopharmaceutical therapy in development for somatostatin receptor expressing (SSTR2+) solid tumors. Alpha-particles (as emitted by 225Ac) have a shorter path length (40-100 mm) and higher linear energy transfer (80-100 keV/mm) than beta-particles, potentially allowing for higher cancer cell kill rates and less damage to healthy tissues. We describe the design of a single-arm, open-label, phase 1b doseescalation and dose-expansion trial of RYZ101 in combination with standard of care (SoC) therapy in patients with SSTR+ extensive-stage small-cell lung cancer (ES-SCLC; NCT05595460). The aim is to determine safety, preliminary antitumor activity, and pharmacokinetics of first-line RYZ101 in combination with carboplatin + etoposide + atezolizumab. Methods: Adult patients with previously untreated, histologically/cytologically confirmed SSTR+ ES-SCLC, ECOG PS 0-1, life expectancy 12 weeks, and sufficient renal, hepatic and hematologic function are eligible. There must be at least 1 SSTR PET imaging-positive (e.g. Gallium-68 [ 68Ga], Copper-64 [64Cu]), not previously irradiated, RECIST v1.1- measurable site of disease; 50% of measurable lesions must be SSTR+. Patients with CNS metastases are permitted but must be asymptomatic and/or adequately treated. Dose escalation: patients receive RYZ101 (i.v. every 6 weeks then every 4 weeks; maximum 6 infusions) starting at 6.5 MBq (dose level 1); dose may be escalated up to 10.2 MBq (dose level 3); intermediate doses may also be explored. Recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) are determined by occurrence of dose-limiting toxicities (DLTs) in the first RYZ101 cycle. Dose expansion: patients receive RYZ101 at the RP2D; patients also receive SoC therapy: atezolizumab (1200 mg i.v. day 1, every 21 days, maximum 4 21-day cycles, then 1680 mg i.v. every 28 days); carboplatin (AUC 5- 6 i.v. over 60 minutes day 1, every 21 days, maximum 4 21-day cycles); etoposide (80-100 mg/mm2 i.v. 60 minutes days 1-3, every 21 days, maximum 4 21-day cycles). Patients may receive their first cycle of platinum-based SoC therapy during the 28-day screening period. Safety is monitored in all patients based on NCI-CTCAE v5.0. Efficacy is evaluated in the efficacy-evaluable population via investigator tumor assessments (RECIST v1.1). Efficacy outcomes: durable objective response rate (ORR); ORR; duration of response; best overall response rate; disease control rate; progression-free survival; overall survival. The dose-escalation portion will enroll up to 18 patients (standard 3+3 design). Up to 12 additional patients may be enrolled at the discretion of the data review committee and study sponsor. In the dose-expansion portion, a total sample size of n¼19 (including patients treated at the MTD/RP2D during the dose-escalation phase) is planned. Approximately 15 sites in the US will participate in the study




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2023 World Conference on Lung Cancer, September 9-12, 2023, Singapore