A Study of Atezolizumab and Tiragolumab Compared With Durvalumab in Participants With Locally Advanced, Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC) (SKYSCRAPER-03)

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

9 Sep 2020 → 1 Aug 2025

Decision date (initial)

2024-07-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche Ltd

External identifiers

EU CT number

2022-502480-38-00

EudraCT number

2019-004773-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others

To evaluate the efficacy of tiragolumab plus atezolizumab compared with durvalumab in the programmed death ligand 1 positive analysis set (PPAS) and in the full analysis set (FAS) on the basis of progression-free survival (PFS), as assessed by an independent review facility (IRF)

Secondary objectives 4

1. To evaluate the efficacy of tiragolumab plus atezolizumab compared with durvalumab in the PPAS and FAS on the basis of overall survival (OS), PFS as assessed by investigator, confirmed objective response rate (ORR) as assessed by an IRF and investigator, DOR as assessed by an IRF and investigator
2. To evaluate the quality of life of patients treated with tiragolumab plus atezolizumab compared with durvalumab in the PPAS and FAS on the basis of time to confirmed deterioration (TTCD)
3. To evaluate the efficacy of tiragolumab plus atezolizumab compared with durvalumab in the PPAS and the FAS on the basis of PFS rate at 12, 18, and 24 months, OS rate at 12, 24, 36, and 48 months, and time to distant metastasis (TTDM)
4. To evaluate the safety and tolerability of tiragolumab plus atezolizumab compared with durvalumab

Conditions and MedDRA coding

Non−small cell lung cancer (NSCLC)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Eastern Cooperative Oncology Group Performance Status of 0 or 1
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 (PET)-CT scan for the purposes of staging, performed prior and within 42 days of the first dose of concurrent chemoradiotherapy (cCRT)
4. At least two prior cycles of platinum-based chemotherapy administered concurrently with radiotherapy (RT), which must be completed within 1 to 42 days prior to randomization in the study (one cycle of cCRT is defined as 21 or 28 days)
5. The RT component in the cCRT must have been at a total dose of radiation of 60 Gy ± 10% (54 Gy to 66 Gy) administered by intensity-modulated radiotherapy (preferred) or 3D-conforming technique
6. No progression during or following concurrent platinum-based CRT

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. Treatment with sequential CRT for locally advanced NSCLC
5. Patients with locally advanced NSCLC who have progressed during or after the definitive cCRT prior to randomization
6. Any Grade > 2 unresolved toxicity from previous CRT

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. PFS, as assessed by an IRF, defined as the time from randomization to the first occurrence of disease progression, as determined by the IRF according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first (PPAS)
2. 2. PFS, as assessed by an IRF (FAS)

Secondary endpoints 11

1. 1. Overall survival (FAS and PPAS)
2. 2. PFS, as assessed by the investigator (FAS and PPAS)
3. 3. Confirmed ORR, as assessed by an IRF (FAS and PPAS)
4. 4. Confirmed ORR, as assessed by the investigator (FAS and PPAS)
5. 5. DOR, as assessed by an IRF (FAS and PPAS)
6. 6. DOR, as assessed by the investigator (FAS and PPAS)
7. 7. Time to confirmed deterioration (TTCD) (FAS and PPAS)
8. 8. PFS rate at 12, 18, and 24 months (FAS and PPAS)
9. 9. OS rate at 12, 24, 36, and 48 months (FAS and PPAS)
10. 10. TTDM (FAS and PPAS)
11. 11. Incidence and severity of adverse events with severity graded 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 2

Comparator 2

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 Town

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 8

Locations

11 EU/EEA countries · 60 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 46 files

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

Application history

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