A Study of Atezolizumab in Patients with Locally Advanced, Unresectable Stage III Non−Small Cell Lung Cancer who have already received chemotherapy and radiotherapy

Start 31 Mar 2022 · End 3 Dec 2025 · Status Ended · 2 EU/EEA countries · 3 sites · Protocol MO43156

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)

Status Ended

Participants planned 130

Countries 2

Sites 3

Non-Small Cell Lung Cancer (NSCLC)

1. To evaluate the efficacy of atezolizumab in patients with locally advanced unresectable Stage III NSCLC who have not progressed after at least two cycles of platinum-based concurrent chemoradiation therapy (cCRT) based on 12-month progression-free survival (PFS) rate

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: 31 Mar 2022 → 3 Dec 2025
Decision date (initial): 2024-02-20
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: 2023-503756-27-00
EudraCT number: 2021-002695-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Secondary objectives 2

1. To evaluate the efficacy of atezolizumab in patients with locally advanced unresectable Stage III NSCLC who have not progressed after at least two cycles of platinum-based cCRT based on independent Review Facility (IRF) and investigator-assessed PFS, overall survival (OS), confirmed objective response rate (ORR), duration of response (DOR), PFS rate, OS rate, and time to death or distant metastasis (TTDM)
2. To evaluate the safety of atezolizumab in patients with locally advanced unresectable Stage III NSCLC who have not progressed after platinum-based cCRT

Conditions and MedDRA coding

Non-Small Cell Lung Cancer (NSCLC)

Version	Level	Code	Term	System organ class
21.1	PT	10029519	Non-small cell lung cancer stage III	100000004864

Study design 4 periods

#	Title	Allocation	Blinding
1	Screening Period Eligible patients will have histologically- or cytologically-documented, locally advanced, unresectable, Stage III NSCLC of either squamous or non-squamous histology that has not progressed following ≥ 2 cycles of platinum-based cCRT (≤ 42 days between the last dose of cCRT and baseline). Staging should be based on the 8th revised edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) NSCLC staging system (Amin et al. 2017). Patients can be either male or female, must be ≥ 18 years of age, must have Eastern Cooperative Oncology Group (ECOG) Performance Status scores of 0 or 1, and must have a known PD-L1 status at screening, as assessed centrally by the investigational VENTANA PD-L1 (SP263) CDx Assay. Tumor tissue for PD-L1 assessment may come from an archival sample or, if an archival sample is unavailable or unsuitable, from a fresh biopsy, so long as the biopsy was performed prior to the first dose of cCRT. Patients whose tumors have a known EGFR mutation or ALK rearrangement will be excluded from enrolment. Patients with tumors of non-squamous histology with unknown EGFR or ALK mutational status will be required to be tested prior to enrolment. Patients with tumors of squamous histology who have an unknown EGFR or ALK mutational status will not be required to be tested. Patients who do not initially meet all of the eligibility criteria for participation in this study may qualify for one re-screening opportunity (for a total of two screenings per patient) at the investigator’s discretion provided the patient completes all rescreening activities within 42 days of receiving the last dose of cCRT. Patients are not required to re-sign the consent form if they are re-screened. For patients who are rescreened, all eligibility criteria must be re-evaluated and screening assessments should be repeated as applicable.	Not Applicable	None
2	Treatment Period Eligible patients will receive atezolizumab by intravenous (IV) infusion at a fixed dose of 1680 mg on Day 1 of each 28-day cycle. Treatment may be continued for up to 13 cycles, so long as the patient is experiencing clinical benefit, as assessed by the investigator, and is not experiencing unacceptable toxicity or symptomatic deterioration attributable to disease progression (after an integrated assessment of radiographic data, biopsy results [if available] and clinical status).	Not Applicable	None
3	Treatment Discontinuation/Completion Visit Patients will report to the clinic ≤ 30 days after the final dose of study treatment for a treatment discontinuation/completion visit. Assessments carried out at the treatment discontinuation/completion visit are described in the schedule of activities.	Not Applicable	None
4	Post-Treatment Follow-Up Patients with confirmed disease progression who have discontinued or completed study treatment will continue to undergo tumor assessments according to local standard of care. Patients who discontinue study treatment for reasons other than disease progression (e.g., toxicity, symptomatic deterioration, completion of study treatment) will continue scheduled tumor assessments as described in the schedule of activities until confirmed radiographic disease progression per RECIST v1.1, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. In the absence of radiographic disease progression, tumor assessments should continue regardless of whether a patient starts a new anticancer therapy. Additional assessments carried out in the post-treatment follow-up period are described in the schedule of activities.	Not Applicable	None

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Ability to comply with the study protocol, including willingness to remain in the post-treatment period
2. Histologically or cytologically documented NSCLC with locally advanced, unresectable Stage III NSCLC of either squamous or non-squamous histology
3. Whole-body positron emission tomography–computed tomography (PET-CT) scan (from the base of skull to mid-thighs) for the purposes of staging, performed prior and within 42 days of the first dose of cCRT
4. At least two prior cycles of platinum-based chemotherapy administered concurrently with radiotherapy (cCRT) completed within 1 to 42 days prior to baseline (one cycle of cCRT is defined as 21 or 28 days)
5. The radiotherapy (RT) component in the cCRT must have been at a total radiation dose of 60 (± 10%) Gy (54 Gy to 66 Gy), administered either as IMRT (preferred) or by 3D-conforming technique.
6. A known Programmed Cell Death 1–Ligand 1 (PD-L1) result, as determined by the investigational Ventana PD-L1 (SP263) CDx Assay and documented by means of central testing of a representative tumor tissue sample, in either a previously obtained archival tumor tissue sample or a fresh tissue sample obtained from a biopsy collected prior to the first dose of cCRT

Exclusion criteria 6

1. Any history of prior NSCLC and/or any history of prior treatment for NSCLC (patients must be newly diagnosed with unresectable Stage III disease)
2. NSCLC known to have a mutation in the epidermal growth factor (EGFR) gene or an anaplastic lymphoma kinase (ALK) fusion oncogene
3. Any evidence of Stage IV disease
4. Any Grade ≥ 2 unresolved toxicity and Grade ≥ 2 pneumonitis from previous cCRT
5. Treatment with sequential CRT for locally advanced NSCLC
6. Patients with locally advanced NSCLC who have progressed during or after definitive cCRT prior to baseline

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 12-month progression-free survival (PFS) rate, defined as the proportion of patients who have not experienced disease progression, as determined by an Independent Review Facility (IRF) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), or death from any cause, at 12 months

Secondary endpoints 9

1. IRF-assessed PFS, defined as the time from initiation of study treatment to the first occurrence of disease progression, as determined by the IRF according to RECIST v1.1, or death from any cause, whichever occurs first
2. Investigator-assessed PFS, defined as the time from initiation of study treatment to the first occurrence of disease progression, as determined by the Investigator according to RECIST v1.1, or death from any cause, whichever occurs first
3. Overall survival (OS), defined as the time from initiation of study treatment to death from any cause
4. Confirmed objective response rate (ORR), defined as the proportion of patients with a confirmed objective response (i.e., complete response [CR] or partial response [PR] on two consecutive occasions ≥ 4 weeks apart), as determined by the IRF and investigator according to RECIST v1.1
5. Duration of response (DOR) in patients with confirmed ORR, defined as the time from the first occurrence of a documented objective response to disease progression as determined by the IRF and investigator according to RECIST v1.1 or death from any cause, whichever occurs first
6. PFS rate at 18 months and 24 months, defined as the proportion of patients who have not experienced disease progression, as determined by the IRF and investigator according to RECIST v1.1, or death from any cause at 18 months and 24 months, respectively
7. OS rate at 12 months, 24 months and 36 months, defined as the proportion of patients who have not died from any cause at 12 months, 24 months and 36 months, respectively
8. Time to death or distant metastasis (TTDM), defined as the time from initiation of study treatment until the first date of distant metastasis or death in the absence of distant metastasis
9. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)

Investigational products

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

Test 1

Tecentriq 840 mg concentrate for solution for infusion

PRD7537925 · Product

Active substance: Atezolizumab
Substance synonyms: RO5541267
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENIOUS INFUSION
Max daily dose: 1680 mg milligram(s)
Max total dose: 22 g gram(s)
Max treatment duration: 12 Month(s)
Authorisation status: Authorised
ATC code: L01FF05 — -
Marketing authorisation: EU/1/17/1220/002
MA holder: ROCHE REGISTRATION GMBH
MA country: Liechtenstein
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: Secondary packaging and labelling for clinical trial use

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 4

Organisation	City, country	Duties
Labcorp Central Laboratory Services S.a.r.l. ORG-100011524	Meyrin, Switzerland	Laboratory analysis
Fortrea Development Limited ORG-100009463	Maidenhead, United Kingdom	Other
Worldcare Clinical LLC ORG-100047766	Waltham, United States	Other
Almac ORG-100013160	Souderton, United States	Other

Locations

2 EU/EEA countries · 3 investigational sites

By country

Country	MS status	Planned subjects	Sites
Slovenia	Ended	8	1
Spain	Ended	5	2
Rest of world Kuwait, Brazil, Panama, Costa Rica, Vietnam, China, Saudi Arabia, Chile, Turkey	—	117	—

Investigational sites

Slovenia

1 site · Ended

Institute Of Oncology Ljubljana

Department of Radiotherapy, Zaloska Cesta 2, 1000, Ljubljana

Spain

2 sites · Ended

Hospital Universitari Vall D Hebron

Servicio de Oncología, Edificio Materno-Infantil, Passeig De La Vall D'hebron 119-129, Barcelona

Hospital Universitario Central De Asturias

Servicio de Oncología, Avenida De Roma S/n, 33011, Oviedo

Country notifications

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

Country	Trial start	Trial end	Recruitment start	Recruitment end	Early termination
Slovenia	2022-04-07	2025-10-24	2022-05-25	2024-08-12
Spain	2022-03-31	2025-11-21	2022-05-26	2024-08-12

Results and documents

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

Summary of results Art. 37(4) CTR

Title	Submission date	Status	Type
MO43156_Summary of Results SUM-137157	2026-06-03T10:22:24	Submitted	Summary of Results

Documents 7 files

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

Type	Title	Version
Protocol (for publication)	D1_Protocol 2023-503756-27-00 Redacted	5
Protocol (for publication)	d1_protocol clarification letter_2023-503756-27-00-redacted	5
Protocol (for publication)	D4_Patient facing documents	NA
Summary of results (for publication)	MO43156 EU CTIS Final Results	N/A
Synopsis of the protocol (for publication)	D1_Protocol synopsis_ENG 2023-503756-27-00	2.0
Synopsis of the protocol (for publication)	D1_Protocol synopsis_ES 2023-503756-27-00	2.0
Synopsis of the protocol (for publication)	D1_Protocol synopsis_SI 2023-503756-27-00	2.0

Application history

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

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2024-01-11	Spain	Acceptable 2024-02-19	2024-02-19
2	SUBSTANTIAL MODIFICATION	SM-1	2024-06-13	Spain	Acceptable 2024-07-24	2024-07-24
3	SUBSTANTIAL MODIFICATION	SM-2	2024-12-02	Spain	Acceptable 2025-01-23	2025-01-23
4	SUBSTANTIAL MODIFICATION	SM-3	2025-09-03	Spain	Acceptable 2025-10-20	2025-10-23