A Phase Ii Study of Adjuvant Atezolizumab or Atezolizumab Plus Tiragolumab in Solid Tumors with Resectable Disease with Intermediate-High Risk of Recurrence and High Tumor Mutational Burden or Microsatellite Instability (IMperator)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Roche Farma S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Mar 2024 → 9 Dec 2024

Decision date (initial)

2024-05-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512635-71-00

EudraCT number

2022-003708-33

ClinicalTrials.gov

NCT06331598

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective for this study is to evaluate the efficacy (DFS) of tiragolumab plus atezolizumab and atezolizumab alone in TMB =13 mut/MB or MSI-H selected patients with solid tumors in the adjuvant setting with intermediate-high risk of relapse.

Secondary objectives 3

1. To evaluate the efficacy of tiragolumab plus atezolizumab and atezolizumab alone.
2. To evaluate the safety and tolerability of atezolizumab and tiragolumab plus atezolizumab.
3. To evaluate the relationship between tumor biomarkers (including but not limited to PD-L1, PD-1, somatic mutations, and others), as defined by IHC or quantitative ddPCR, next generation sequencing, and/or other methods and measures of efficacy, tumor progression, as well as potential resistance to immunotherapy.

Conditions and MedDRA coding

Solid tumors

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Signed Informed Consent Form (ICF)
2. Male or female, 18 years of age or older
3. ECOG performance status of 0 to 1
4. Solid tumors considered to be resectable with a curative intent with known high TMB/MSI-H
5. Patients must undergo standard treatment according to the stage of their disease. Patients who are ineligible for adjuvant therapy can be included if they complete the prescreening within 50 days post-surgery and are enrolled in the study within 90 days post-surgery
6. All patients must be disease free after standard therapy to be included in this study
7. TMB ≥ 13 mut/MB or MSI-H in tumor tissue biopsy
8. Patients must be at intermediate/high risk of recurrence
9. Adequate hematologic and organ function
10. For female patients of childbearing potential, agreement to use a highly effective form(s) of contraception that results in a low failure rate when used consistently and correctly
11. For male patients with female partners of childbearing potential, agreement to use a highly effective form(s) of contraception that results in a low failure rate when used consistently and correctly
12. Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drugs
13. Women not postmenopausal or surgically sterile must have a negative serum pregnancy test result. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy.

Exclusion criteria 18

1. Previous malignancies within 3 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
2. Patients with illnesses or conditions that interfere with their capacity to understand, follow, and/or comply with study procedures
3. Prior cancer immunotherapy
4. Any contraindication for surgery and/or systemic therapy and cancer immunotherapy
5. Known serine/threonine kinase 11 (STK-11) ligand alterations, mouse double minute 2 (MDM2) homolog amplifications
6. Women who are pregnant, lactating, or intending to become pregnant during the study
7. History of autoimmune disease
8. Positive test for human immunodeficiency virus
9. Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen test at screening) or hepatitis C
10. History of idiopathic pulmonary fibrosis, organizing pneumonia, druginduced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
11. Severe infections within 4 weeks prior to be included in the study
12. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to inclusion, unstable arrhythmias, or unstable angina
13. Treatment with systemic immunosuppressive medications within 2 weeks prior to inclusion
14. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications
15. Active tuberculosis
16. Major surgical procedure within 28 days prior to study treatment or anticipation of need for a major surgical procedure during the course of the study
17. Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation that such a live attenuated vaccine will be required during the study
18. Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives of the drug, whichever is longer, prior to randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the Disease Free Survival (DFS) rate at 24 months defined as the proportion of patients who have not suffered any of the following since the time of randomization: first documented recurrence of disease, new primary tumor or death due to any cause, whichever occurs first

Secondary endpoints 6

1. DFS rate at 36, 48 and 60 months
2. OS (Overall Survival) after randomization, defined as the time from randomization to death from any cause
3. Incidence and severity of AEs, with severity determined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0)
4. Change from baseline in targeted clinical laboratory test results
5. Tumor biomarker: Percentage of PDL1 positive cells versus DFS and OS
6. Genomics: Genomic alterations related to resistance to immunotherapy versus DFS and OS

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Roche Farma S.A.

Sponsor organisation

Roche Farma S.A.

Address

Calle De La Ribera Del Loira 50

City

Madrid

Postcode

28042

Country

Spain

Scientific contact point

Organisation

Roche Farma S.A.

Contact name

Susana Pons

Public contact point

Organisation

Roche Farma S.A.

Contact name

Susana Pons

Third parties 2

Locations

1 EU/EEA country · 3 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 9 files

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

Application history

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