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

Document Type

Conference Proceeding

Publication Date

11-2023

Publication Title

Journal of Thoracic Oncology

Abstract

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

Volume

18

Issue

11 Suppl.

First Page

S375

Last Page

S376

Comments

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

DOI

10.1016/j.jtho.2023.09.664

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