A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Jan 2024 → ongoing

Decision date (initial)

2024-02-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-503920-14-00

EudraCT number

2021-004149-19

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of study treatment (alectinib or entrectinib) compared with durvalumab in patients with biomarker-selected, locally advanced, unresectable, Stage III NSCLC who have received concurrent chemoradiotherapy (cCRT) or sequential chemoradiotherapy (sCRT) and have not had radiographic disease progression with respect to Blinded Independent Central Review (BICR)- Progression-free survival (PFS)

Secondary objectives 3

1. To evaluate the efficacy of study treatment (alectinib or entrectinib) compared with durvalumab in patients with biomarker-selected locally advanced, unresectable Stage III Non-small cell lung cancer NSCLC who have received cCRT or sCRT and have not had radiographic disease progression with respect to - time to CNS progression, distant metastasis-free survival (DMFS), duration of response (DOR), and objective response rate (ORR) as determined by the BICR per RECIST v1.1 - PFS, duration of response (DOR), time to CNS progression, distant metastasis-free survival (DMFS), and overall survival (OS) as determined by the investigator per RECIST v1.1
2. To evaluate the health-related quality of life of patients with biomarker-selected locally advanced, unresectable, Stage III NSCLC who have received cCRT or sCRT and have not had radiographic disease progression in the study treatment arm compared with in the durvalumab arm
3. To evaluate the safety and tolerability of study treatment compared with durvalumab in patients with biomarker selected, locally advanced, unresectable, Stage III NSCLC who have received cCRT or sCRT and have not had radiographic disease progression

Conditions and MedDRA coding

Non-Small Cell Lung Cancer (NSCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Whole-body positron emission tomography/computed tomography scan (PET-CT) performed prior and within 42 for Cohort A2 (ROS1 positive) and 50 days for Cohort A1 (ALK positive) days of the first dose of cCRT or sCRT
2. Histologically or cytologically documented locally advanced, unresectable Stage III NSCLC of either squamous or non-squamous histology (Version 8, American Joint Committee on Cancer/Union for International Cancer Control NSCLC staging system)
3. No disease progression during or following receipt of at least 2 cycles of platinum-based cCRT or sCRT
4. Documented ALK fusion positivity (Cohort A1)
5. Documented ROS1 fusion positivity (Cohort A2)
6. Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2

Exclusion criteria 6

1. Any history of previous NSCLC and/or any history of prior treatment for NSCLC
2. Any evidence of Stage IV disease
3. NSCLC known to have a known or likely oncogenic-driver mutation in the EGFR gene, as identified by site local testing or Sponsor central testing
4. Prior treatment with ALK inhibitors (Cohort A1)
5. Prior treatment with ROS1 inhibitors (Cohort A2)
6. Active or history of autoimmune disease or immune deficiency

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Progression-free survival (PFS), as determined by Blinded independent central review (BICR) per RECIST v1.1

Secondary endpoints 10

1. 1. PFS, defined as the time from randomization to the first documented disease progression, as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurs first
2. 2. Time to central nervous system (CNS) progression, as determined by BICR and investigator per RECIST v1.1
3. 3. Distant metastasis-free survival (DMFS), as determined by BICR and investigator per RECIST v1.1
4. 4. Objective response rate (ORR), as determined by BICR and investigator per RECIST v1.1
5. 5. Duration of response (DOR), as determined by BICR and investigator per RECIST v1.1
6. 6. Overall survival (OS)
7. 7. Time-to-confirmed deterioration (TTCD), in the following patient-reported scales and lung cancer symptoms: Physical functioning, Role functioning, Cough, Chest pain, Dyspnea
8. 8. Change from baseline score as measured through the use of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at 5, 11, and 17 months in the following patient-reported scales and lung cancer symptoms: Physical functioning, Role functioning, Cough, Chest pain, Dyspnea
9. 9. Incidence, type, and severity of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
10. 10. Changes in vital signs, physical findings, and clinical laboratory results during and following administration of protocol-specified investigational medicinal products (IMPs)

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 9

Locations

9 EU/EEA countries · 44 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 147 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