A Phase II, single-arm trial of Atezolizumab/Platinum/Etoposide for the treatment of advanced large-cell neuroendocrine cancer of the lung (LCNEC-ALPINE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Technische Universitaet Dresden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Jan 2022 → ongoing

Decision date (initial)

2024-10-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

ROCHE Pharma AG

External identifiers

EU CT number

2024-515902-15-00

EudraCT number

2020-002683-31

ClinicalTrials.gov

NCT05470595

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective of this trial is to evaluate the efficacy of Atezolizumab in addition to standard of care (SoC) chemotherapy for the treatment of LCNEC as measured by overall survival (OS).

Secondary objectives 2

1. to assess the safety and tolerability of Atezolizumab in addition to standard of care (SoC)
2. to assess efficacy of Atezolizumab in addition to SoC by response rate, duration of response (DoR) and progression free survival (PFS) according to standard and immunotherapy-specific response criteria

Conditions and MedDRA coding

Male and female adult patients with locally advanced or metastatic large-cell neuroendocrine carcinoma of the lung not eligible for curative treatment

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Written informed consent
2. Patients with locally advanced or metastatic large-cell neuroendocrine carcinoma of the lung (LCNEC) without curative treatment options (patients with mixed histology are eligible if LCNEC is the predominant histology i.e. ≥50%)
3. Previously untreated with systemic therapy (note: patients relapsing after curative radio chemotherapy or adjuvant chemotherapy are eligible if relapse occurs ≥6 months after discontinuation of curative treatment)
4. Planned treatment with Carboplatin or Cisplatin and Etoposide (standard of care - SoC)
5. Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
6. age ≥18 years
7. measurable disease according to RECIST v1.1
8. adequate organ function defined as: Alanine Aminotransferase (ALAT) / Aspartate Aminotransferase (ASAT) ≤2.5x ULN or ≤3.5x Upper limit of Normal (ULN) in case of liver metastases; Bilirubin ≤1.5x ULN or ≤2.5x ULN in case of liver metastases; Creatinine ≤1.5x ULN or Creatinine clearance according to Cockroft-Gault >60 ml/min; Neutrophils ≥1 Gigaparticle (Gpt)/l, Platelets >50 Gpt/l unless caused by bone marrow carcinosis

Exclusion criteria 5

1. Symptomatic brain metastases (patients with asymptomatic brain metastases are allowed provided they are stable without steroid treatment for at least 3 weeks)
2. Severe autoimmune disease (patients with endocrine autoimmune disorders are allowed as long as they are on stable substitution treatment)
3. Severe uncontrolled infection
4. Prior treatment with either Atezolizumab or other immune checkpoint inhibitor
5. Any prior treatment for metastatic disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS, time to event endpoint, measured from cycle 1 day 1 (C1D1) to death from any cause)

Secondary endpoints 10

1. Objective response rate (ORR) defined as partial remission (PR) or complete remission (CR) according to RECIST v1.1
2. Immune ORR (iORR) defined as immune PR (iPR) or immune CR (iCR) according to iRECIST
3. Disease control rate (DCR) defined as combination of CR, PR and stable disease (SD) according to RECIST v1.1
4. Progression free survival (PFS) defined as time from C1D1 to progression according to RECIST v1.1, or to start of any other anticancer treatment, or death from any cause whichever occurs first
5. Immune PFS (iPFS) defined as time from C1D1 to progression according to iRECIST or death from any cause whichever occurs first
6. Duration of response (DoR) defined as time from first documented PR or CR according to RECIST v1.1 to time of disease progression according to RECIST v1.1 or death from any cause whichever occurs first
7. PFS/ iPFS (according to RECIST v1.1 and iRECIST) rate at 1 year
8. OS rate at 1 year
9. PFS, OS, DoR and ORR in central pathology confirmed cases of LCNEC
10. Incidence, nature, severity of adverse events (grading according to NCI CTCAE (v5.0)

Investigational products

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

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Technische Universitaet Dresden

Sponsor organisation

Technische Universitaet Dresden

Address

Mommsenstrasse 11, Raecknitz/zschertnitz Raecknitz/zschertnitz

City

Dresden

Postcode

01069

Country

Germany

Scientific contact point

Organisation

Technische Universitaet Dresden

Contact name

Prof. Dr. Martin Wermke

Public contact point

Organisation

Technische Universitaet Dresden

Contact name

Prof. Dr. Martin Wermke

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 8 files

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

Application history

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