A Phase Ib/II Dose Finding Study Assessing Safety and Efficacy of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Extensive Stage Small Cell Lung Cancer (ES-SCLC) in Combination With Carboplatin, Etoposide, and Atezolizumab in Induction and With Atezolizumab in Maintenance Phase

Brief Summary

Detailed 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 declaring 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).

Primary Outcomes

Secondary Outcomes

• Phase lb: Objective Response Rate (ORR) based on Investigator assessment(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final Overall Survival (OS) analysis))
• Phase lb: Duration of Response (DOR)(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final Overall Survival (OS) analysis))
• Phase lb: Progression Free Survival (PFS) based on Investigator assessment(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final OS analysis))
• Phase lb: Overall Survival (OS)(From date of randomization until date of death from any cause, assessed up to 3 years (estimated final Overall Survival (OS) analysis))
• Phase ll: Progression free survival (PFS) by investigator assessment(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final OS analysis))
• Phase ll: Objective Response Rate (ORR) by investigator assessment(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final Overall Survival (OS) analysis))
• Phase ll: Duration of Response (DOR) by investigator assessment(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final Overall Survival (OS) analysis))
• Incidence and severity of adverse events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, and ECGs; dose interruptions, discontinuations, and reductions(From date of randomisation until date of progression or date of death from any cause, whichever comes first, assessed for up to 3 years)
• Incidence and severity of Adverse Events (AEs) and serious Adverse Events (SAEs) within 48 hours after [68Ga]Ga-DOTA-TATE infusion(up to 48 hours following the start of [68Ga]Ga-DOTA-TATE administration])
• Phase lb and II: Absorbed radiation doses of [177Lu]Lu-DOTA-TATE(Week 7 Day 3)
• Phase lb: PK parameters of [177Lu]Lu-DOTA-TATE in blood(Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose))
• Phase II: PK parameters of [177Lu]Lu-DOTA-TATE in blood(Week 1 Day 3, Week 7 Day 3 (pre-dose, before the end of infusion, post-dose: 2 hours, 6 hours, 24 hours, 48 hours, 168 hours), Week 13 Day 1 (pre-dose, before the end of infusion, post-dose: 2 hours, 6 hours, 24 hours, 48 hours post-dose))