Overview
This study aims to establish a safe and well tolerated dose of [177Lu]Lu-DOTA-TATE in combination with carboplatin, etoposide and atezolizumab in this setting and to assess preliminary efficacy of this combination treatment versus the combination of carboplatin, etoposide, and atezolizumab.The study will be essential to assess a new potential therapeutic option in participants with this aggressive cancer type.
Description
The study for each participant consists of a Screening period, a Treatment period that includes an Induction treatment period and a Maintenance treatment period, and a Follow-up period.
The study will consist of a Phase Ib dose escalation with concurrent backfill part and a randomised controlled Phase II part.
During the screening period of up to 28 days before starting SCLC treatment, each participant will be assessed for somatostatin receptor (SSTR) expression by [68Ga]Ga-DOTA-TATE imaging PET/scan.
The dose escalation part in this study will be guided by the dose limiting toxicity (DLT) rate observed during the DLT period. To achieve a more robust dataset and to aid dose decisions, additional participants may be backfilled in each dose level.
Upon dedclaring RD, a 1:1 randomised Phase II with approximately 140 participants with newly diagnosed ES-SCLC will be enrolled and receive either [177Lu]Lu-DOTA-TATE at the RD in combination with carboplatin, etoposide and atezolizumab (experimental arm) or carboplatin, etoposide and atezolizumab alone (control arm).
Eligibility
Key Inclusion Criteria:
- Participant is >= 18 years on the day of signing informed consent form
- Histologically or cytologically confirmed ES-SCLC
- Presence of measurable disease (at least one target lesion) according to RECIST v1.1 assessed by conventional computed tomography (CT) scan
- No prior systemic treatment for ES-SCLC (except the first cycle of chemotherapy with or without atezolizumab of the induction period
- ECOG status =< 1
- Provision of tumor tissue to support exploratory biomarker analysis
- Life expectancy of >= 6 months
Key Exclusion Criteria:
- Participant has received prior therapy with an antibody or drug against immune checkpoint pathways
- Active autoimmune diseases or history of autoimmune diseases that may relapse
- Severe chronic or active infections (including active tuberculosis, HBV, or HCV infection) requiring systemic antibacterial, antifungal or antiviral therapy within 2 weeks before Cycle 1 Day 1
- Any major surgical procedure requiring general anesthesia =< 28 days before Cycle 1 Day 1
- History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for participants participating in the study
- Known hypersensitivity to the active substances or any of the excipients of the study drugs
- Concurrent participation in another therapeutic clinical study