A Study of Atezolizumab with or without Tiragolumab in Participants with Unresectable Esophageal Squamous Cell Carcinoma whose Cancers have not Progressed Following Definitive Concurrent Chemoradiotherapy (SKYSCRAPER-07)

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

27 Oct 2020 → ongoing

Decision date (initial)

2024-07-23

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

2022-502052-30-00

EudraCT number

2020-001178-31

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Efficacy, Safety

To evaluate the efficacy of tiragolumab+atezolizumab compared with double placebo based on investigator assessed progression free survival (PFS) and overall survival (OS) and to evaluate the efficacy of placebo+atezolizumab compared with double placebo based on investigator assessed OS

Secondary objectives 6

1. 1. To evaluate the efficacy of placebo + atezolizumab compared with double placebo on the basis of investigator and IRF assessed progression-free survival
2. 2. To evaluate the efficacy of tiragolumab + atezolizumab versus placebo + atezolizumab to demonstrate the contribution of tiragolumab
3. 3. To evaluate the efficacy of tiragolumab+atezolizumab and placebo+atezolizumab compared with double placebo and the efficacy of tiragolumab atezolizumab versus placebo + atezolizumab to demonstrate the contribution of tiragolumab
4. 4. To evaluate safety and tolerability of tiragolumab + atezolizumab and placebo + atezolizumab compared with double placebo
5. 5. To characterize pharmacokinetics of tiragolumab and atezolizumab
6. 6. To evaluate immune response to tiragolumab and atezolizumab

Conditions and MedDRA coding

Unresectable Esophageal Squamous Cell Carcinoma

Study design 1 period

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. Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the esophagus
2. Definitive concurrent chemoradiotherapy (dCRT) treatment according to regional oncology guidelines (Such as National Comprehensive Cancer Network [NCCN; see Appendix 10 for recommended treatment], European Society for Medical Oncology [ESMO], Chinese Society of Clinical Oncology [CSCO], etc.) for esophageal cancer and with the following criteria: Patients with inoperable cancer must have received at least 2 cycles of platinum-based chemotherapy and radiation therapy consistent with definitive treatment (50-64 Gy) without evidence of radiographic disease progression per RECIST v1.1, as documented by comparison of scans (pre- and post-dCRT) prior to randomization. Patients with cervical esophageal squamous cell carcinoma may receive higher radiation dose (50-66 Gy), as per local oncology guidelines. Randomization into the study must occur within 1-84 days after the last dose of radiation therapy. Use of herbal therapies/traditional Chinese medicines with anti-cancer activity intended to treat the disease under the study must be discontinued prior to randomization.
3. Stage II-IVA per American Joint Committee on Cancer/Union for International Cancer Control, 8th edition, unresectable locally advanced disease (medically or surgery is declined) prior to definitive concurrent chemoradiotherapy (dCRT) – Patients are not expected to undergo tumor resection during the course of the study. – Ineligibility for curative surgery must be based on the documented opinion of the qualified medical, surgical or radiation oncologist. – Stage IVB patients diagnosed with cervical or upper thoracic esophageal squamous cell carcinoma with supraclavicular lymph node metastases only and are deemed suitable for definitive concurrent chemoradiation therapy in the opinion of the treating physician, multidisciplinary team or tumor board are eligible
4. Representative archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens < 12 months old, collected prior to initiation of dCRT in either paraffin blocks (preferred over slides) or approximately 10-15 slides (15 slides preferred) containing unstained, freshly cut, serial sections (of the 10-15 slides, 5 are for the stratification PD-L1 testing). The number of slides provided may also be governed by local regulations (e.g., Human Genetic Resources Administration of China) Tumor tissue must be submitted for PD-L1 (SP263) expression evaluation prior to randomization. Tumor tissue should be of good quality based on total and viable tumor content and be submitted with an associated pathology report. Patients whose tumor tissue is not evaluable for PD-L1 expression are not eligible. For the purpose of stratification, the PD-L1 score of the patient’s tumor will be the highest PD-L1 TIC score among all samples tested from a single patient prior to stratification, if multiple samples are submitted. Acceptable samples include core needle biopsies for deep tumor tissue or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. FFPE tumor specimens in paraffin blocks are preferred. Fine-needle aspiration, brushing, cell pellet from effusions and lavage samples are not acceptable.
5. Patients without hepatitis B virus (HBV) infection or for patients with a positive hepatitis B surface antigen (HBsAg) test and/or a positive total hepatitis B core antibody (HBcAb) test in the absence of a positive hepatitis B surface antibody (HBsAb) test at screening: HBV DNA < 500 IU/mL Patients with detectable HBV DNA should be managed per institutional guidelines. Initiation of anti-HBV therapy should be ≥ 14 days prior to initiation
6. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening The HCV RNA test will be performed only for patients who have a positive HCV antibody test.

Exclusion criteria 6

1. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-T-cell immunoreceptor with Ig and ITIM domains (TIGIT) therapeutic antibodies
2. Any unresolved toxicity of NCI CTCAE Grade ≥ 2 from the prior chemoradiation therapy Patients with irreversible and manageable hearing loss are eligible.
3. Evidence of complete esophageal obstruction not amenable to treatment
4. Histology consistent with small cell esophageal carcinoma, esophageal adenocarcinoma, or mixed carcinoma
5. High risk for developing esophageal fistula by clinical assessment or imaging, such as prior history or associated symptoms of esophageal fistula, or primary tumor invasion of the great vessels or trachea
6. Prior esophagectomy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 1. Progression-Free Survival as determined by the investigator (for tiragolumab + atezolizumab compared with double placebo)
2. 2. Overall survival (for tiragolumab + atezolizumab compared with double placebo)
3. 3. Overall Survival (for placebo + atezolizumab compared with double placebo)

Secondary endpoints 14

1. 1. Progression-Free Survival as determined by the investigator (for placebo + atezolizumab compared with double placebo)
2. 2. Progression-Free Survival as determined by the investigator (for tiragolumab + atezolizumab compared with placebo + atezolizumab)
3. 3. Overall Survival (for tiragolumab + atezolizumab compared with placebo + atezolizumab)
4. 4. Progression-Free Survival as determined by the independent review facility (IRF) (for tiragolumab + atezolizumab compared with placebo + atezolizumab and double placebo)
5. 5. Confirmed ORR as determined by the investigator (for tiragolumab + atezolizumab compared with placebo + atezolizumab and double placebo)
6. 6. Confirmed ORR as determined by an IRF
7. 7. Duration of response as determined by the investigator
8. 8. Duration of response as determined by the IRF
9. 9. Proportion of patients with clinically meaningful changes in physical functioning, role functioning, global health status/quality of life, and dysphagia, as measured by the respective scales of the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire and the European Organisation for Research and Treatment of Cancer Quality of Life-Esophageal Cancer, Module 18 Questionnaire
10. 10. Incidence and severity of adverse events
11. 11. Severity for all events will be graded according to NCI CTCAE v5.0, and severity for CRS will also be graded according to the ASTCT consensus grading scale.
12. 12. Serum concentration of tiragolumab and atezolizumab at specified timepoints
13. 13. Prevalence of anti-drug antibody (ADAs) to tiragolumab at baseline and incidence of ADAs to tiragolumab during the study
14. 14. Prevalence of ADAs to atezolizumab at baseline and incidence of ADAs to atezolizumab during the study

Investigational products

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

Test 2

Placebo 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 10

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 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