A Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed ES-SCLC Patients in Combination With Carboplatin, Etoposide and Atezolizumab

Novartis

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Extensive Stage Small Cell Lung Cancer

Treatments: Other: Carboplatin; Other: Etoposide; Drug: Atezolizumab; Drug: [68Ga]Ga-DOTA-TATE; Drug: [177Lu]Lu-DOTA-TATE

Study type: Interventional

Funder types: Industry

Identifiers

NCT05142696

CAAA601A42101

2024-513185-19-00 (Other Identifier)

2021-004155-16 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 24 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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24 participants in 8 patient groups

Dose Level 1 (DL1)

Experimental group

Description:

Dose Level 1 (DL1): \[177Lu\]Lu-DOTA-TATE 100 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 100 mCi plus atezolizumab 1200 mg in the maintenance period.

Treatment:

Drug: [68Ga]Ga-DOTA-TATE

Drug: [177Lu]Lu-DOTA-TATE

Drug: Atezolizumab

Other: Etoposide

Other: Carboplatin

Dose Level 2a (DL2a)

Experimental group

Description:

Dose Level 2a (DL2a): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 150 mCi plus atezolizumab 1200 mg in the maintenance period.

Treatment:

Drug: [68Ga]Ga-DOTA-TATE

Drug: [177Lu]Lu-DOTA-TATE

Drug: Atezolizumab

Other: Etoposide

Other: Carboplatin

Dose Level 2b (DL2b)

Experimental group

Description:

Dose Level 2b (DL2b): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumad 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 in the maintenance period.

Treatment:

Drug: [68Ga]Ga-DOTA-TATE

Drug: [177Lu]Lu-DOTA-TATE

Drug: Atezolizumab

Other: Etoposide

Other: Carboplatin

Dose Level 3a (DL3a)

Experimental group

Description:

Dose Level 3a (DL3a): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 mg in the maintenance period.

Treatment:

Drug: [68Ga]Ga-DOTA-TATE

Drug: [177Lu]Lu-DOTA-TATE

Drug: Atezolizumab

Other: Etoposide

Other: Carboplatin

Dose Level 3b (DL3b)

Experimental group

Description:

Dose Level 3b (DL3b): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.

Treatment:

Drug: [68Ga]Ga-DOTA-TATE

Drug: [177Lu]Lu-DOTA-TATE

Drug: Atezolizumab

Other: Etoposide

Other: Carboplatin

Dose Level 4 (DL4)

Experimental group

Description:

Dose Level 4 (DL4): \[177Lu\]Lu-DOTA-TATE 250 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.

Treatment:

Drug: [68Ga]Ga-DOTA-TATE

Drug: [177Lu]Lu-DOTA-TATE

Drug: Atezolizumab

Other: Etoposide

Other: Carboplatin

Phase II Experimental arm

Experimental group

Description:

\[177Lu\]Lu-DOTA-TATE at recommended dose declared in phase I part in combination with carboplatin, etoposide and atezolizumab (experimental arm)

Treatment:

Drug: [68Ga]Ga-DOTA-TATE

Drug: Atezolizumab

Other: Etoposide

Other: Carboplatin

Phase II Control arm

Other group

Description:

Carboplatin, etoposide and atezolizumab alone (control arm)

Treatment:

Drug: [68Ga]Ga-DOTA-TATE

Drug: Atezolizumab

Other: Etoposide

Other: Carboplatin