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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Jul 2022 → ongoing

Decision date (initial)

2025-06-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2024-513185-19-00

EudraCT number

2021-004155-16

ClinicalTrials.gov

NCT05142696

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Others, Pharmacokinetic, Therapy, Safety, Efficacy, Dose response

• Phase Ib: To establish the recommended dose of [177Lu]Lu-DOTA-TATE in combination with carboplatin, etoposide, and atezolizumab in induction treatment and with atezolizumab in maintenance treatment in newly diagnosed participants with ES-SCLC
• Phase II: To assess efficacy of [177Lu]Lu-DOTA-TATE in combination with carboplatin, etoposide and atezolizumab (experimental arm) versus standard of care consisting of carboplatin, etoposide, and atezolizumab (control arm) in terms of overall survival

Secondary objectives 1

1. Phase Ib: • To assess the preliminary anti-tumor activity of [177Lu]Lu-DOTA-TATE in combination with carboplatin, etoposide and atezolizumab in newly diagnosed participants with ES-SCLC • To characterize the pharmacokinetics (PK) and dosimetry of [177Lu]Lu-DOTA-TATE in participants with newly diagnosed participants with ES-SCLC Phase II: • To evaluate the antitumor activity of [177Lu]Lu-DOTA-TATE in combination with carboplatin, etoposide and atezolizumab (experimental arm) versus standard of care consisting of carboplatin, etoposide, and atezolizumab (control arm) Phase Ib and Phase II : • To characterize the safety and tolerability of [177Lu]Lu-DOTA-TATE in combination with carboplatin, etoposide, and atezolizumab in induction treatment and with atezolizumab in maintenance treatment in newly diagnosed participants with ES-SCLC • To assess the safety and tolerability of [68Ga]Ga-DOTA-TATE in participants with newly diagnosed ES-SCLC

Conditions and MedDRA coding

Extensive stage small cell lung cancer (ES-SCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • 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 • SSTR positive [68Ga]Ga-DOTA-TATE imaging positron emission tomography (PET) scan demonstrating uptake equal or higher than the liver uptake (uptake intensity score 2 or above in the visual uptake scoring scale) in at least one target or non-target lesion • No prior systemic treatment for ES-SCLC (except the first cycle of chemotherapy with or without atezolizumab of the induction period) • Provision of tumor tissue to support exploratory biomarker analysis •Life expectancy of >=6 months

Exclusion criteria 1

1. • Participant has received prior therapy with an antibody or drug against immune checkpoint pathways • Active leptomeningeal disease or uncontrolled, untreated brain metastasis • Any major surgical procedure requiring general anesthesia =< 28 days before Cycle 2 Day 1 • History of 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Phase Ib: • Frequency of dose limiting toxicities (DLTs), incidence of adverse events (AEs), serious AEs (SAEs), and AEs leading to treatment discontinuation Phase II: • Overall Survival (OS) defined as time from date of randomization to death due to any cause

Secondary endpoints 1

1. Phase Ib:•ORR,DOR,PFS,OS •TACs •Absorbed radiation doses of [177Lu]Lu-DOTA-TATE in organs and tumor lesions •Concentration of [177Lu]Lu-DOTA-TATE in blood over time and derived PK parameters •Quantification of [177Lu]Lu-DOTA-TATE excreted from the body in urine Phase II:•PFS,ORR,DOR based on investigator assessment as per RECIST 1.1 Phase Ib and Phase II:•Incidence and severity of AEs and SAEs •Incidence and severity of AEs and SAEs within 48 hours after [68Ga]Ga-DOTA-TATE infusion

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 14

Locations

8 EU/EEA countries · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 116 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications