A Study Evaluating the Efficacy and Safety of Neoadjuvant Treatment with Atezolizumab or Placebo in Combination with Platinum-Based Chemotherapy in Patients with Resectable Stage II, IIIA, or Select IIIB Non-small cell lung cancer

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

4 Apr 2018 → 1 Jan 2026

Decision date (initial)

2024-03-04

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

2023-504209-35-00

EudraCT number

2017-002857-12

ClinicalTrials.gov

NCT03456063

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Efficacy, Safety

To evaluate the efficacy of neoadjuvant treatment with atezolizumab in combination with platinum-based chemotherapy followed by adjuvant atezolizumab based on independent review facility (IRF) -assessed event-free survival (EFS)

Secondary objectives 6

1. Efficacy of neoadjuvant treatment with atezolizumab in combination with platinum-based chemotherapy based on pathological complete response (pCR), major pathological response (MPR), and objective response rate
2. Efficacy of neoadjuvant treatment with atezolizumab in combination with platinum-based chemotherapy followed by adjuvant atezolizumab based on overall survival (OS), investigator assessed EFS and disease-free survival (DFS), 2-year and 3-year OS, 2-year and 3-year investigator and IRF assessed EFS
3. Patient reported outcomes of health-related quality of life assessments associated with atezolizumab in combination with platinum-based chemotherapy as neoadjuvant treatment followed by adjuvant atezolizumab
4. Safety of neoadjuvant treatment with atezolizumab in combination with platinum-based chemotherapy followed by adjuvant atezolizumab based on occurrence and severity of adverse events, surgical outcomes and measures to evaluate surgical safety.
5. Immune response to atezolizumab
6. Pharmacokinetic (PK) profile of atezolizumab when given in combination with platinum-based chemotherapy and PK profile of atezolizumab alone

Conditions and MedDRA coding

Early-Stage Resectable Non-small cell lung cancer (NSCLC)

Study design 5 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Age ≥ 18 years
2. 2. Eligibility to receive a platinum-based chemotherapy regimen
3. 3. Pathologically documented Stage II, IIIA, or select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology Staging should be based on the 8th edition of the American Joint Committee on Cancer / Union Internationale Contre le Cancer NSCLC staging system- T4 primary NSCLC will be allowed only on the basis of size (tumors > 7 cm).
4. 4. Solid or subsolid appearance of NSCLC on CT scan with no appearance of purely ground-glass opacity (GGO)
5. 5. Eligible for R0 resection with curative intent
6. 6. Adequate pulmonary, cardiac, hematologic and end-organ function to be eligible for surgical resection with curative intent, as assessed by Pulmonary function tests (PFTs)

Exclusion criteria 6

1. 1. Illness or condition that may interfere with a patient's capacity to understand, follow, and/or comply with study procedures
2. 2. NSCLC with histology of large cell neuroendocrine carcinoma or sarcomatoid carcinoma
3. 3. Mixed NSCLC and small cell lung cancer histology
4. 4. Any prior therapy for lung cancer, including chemotherapy or radiotherapy
5. 5. Major surgical procedure, other than for diagnosis, within 28 days prior to initiation of study treatment, or anticipation of need for non-protocol- -mandated major surgical procedure during the study
6. 6. Activating mutation in the epidermal growth factor receptor (EGFR) or with an anaplastic lymphoma kinase (ALK) fusion oncogene

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. IRF-assessed EFS

Secondary endpoints 13

1. 1. IRF-assessed pCR
2. 2. IRF-assessed MPR
3. 3. MPR and pCR, as assessed by the investigator site pathology laboratory
4. 4. Objective response by the investigator according to RECIST v1.1
5. 5. OS
6. 6. Investigator-assessed EFS
7. 7. DFS as determined by the investigator
8. 8. 2-year and 3-year OS, IRF assessed EFS and investigator-assessed EFS
9. 9. Change from baseline in health-related quality of life (HRQoL) scores as assessed through use of the two-item global health status (GHS)/ QoL subscale (Questions 29 and 30) of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 at each assessment time point during the study through the completion of adjuvant treatment and observation follow up assessments
10. 10. Occurrence and severity of adverse events, including serious adverse events and immune-related adverse events, with severity determined according to NCI CTCAE v5.0
11. 11. Incidence and length of surgical delays, incidence of operative and post-operative complications, and/or reasons for surgical cancellations
12. 12. Serum concentration of atezolizumab at specified timepoints
13. 13. Incidence of anti-drug antibodies (ADAs) against atezolizumab during the study

Investigational products

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

Test 2

Placebo 1

Auxiliary 4

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 7

Locations

8 EU/EEA countries · 42 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 44 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