A study to look at how safe and effective glofitamab plus R-CHOP in ctDNA high-risk people with untreated diffuse large B-cell lymphoma

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

12 Jun 2020 → ongoing

Decision date (initial)

2024-05-17

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

2023-504994-19-00

EudraCT number

2021-001647-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

To evaluate the efficacy of glofitamab in combination with R-CHOP in circulating-tumor DNA (ctDNA) high-risk patients with previously untreated DLBCL based on end of treatment (EOT) complete response (CR) rate as determined by the investigator according to 2014 Lugano Response Criteria

Secondary objectives 4

1. To evaluate the efficacy of glofitamab in combination with R-CHOP in ctDNA high-risk patients with previously untreated DLBCL based on objective response rate (ORR) at the EOT, progression-free survival (PFS) and overall survival (OS) as determined by the investigator according to 2014 Lugano Response Criteria
2. To evaluate the safety of glofitamab in combination with R-CHOP in ctDNA high-risk participants with DLBCL
3. To characterize the serum pharmacokinetics (PK) profile of glofitamab in combination with R-CHOP
4. To evaluate potential effects of anti-drug antibodies (ADAs)

Conditions and MedDRA coding

Diffuse Large B-Cell Lymphoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Previously untreated patients with cluster of differential (CD20)-positive DLBCL, including diagnoses by the 2016 World Health Organization (WHO) classification of lymphoid neoplasms
2. International Prognostic Index (IPI): 1-5
3. Life expectancy of >=6 months
4. Adequate biomarker blood samples prior to initiation of R-CHOP on Day 1 of Cycle 1 and on Day 1 of Cycle 2 submitted for screening for determination of ctDNA status
5. At least one bi-dimensionally fluorodeoxyglucose (FDG)-avid measurable lymphoma lesion on positron emission tomography/computed tomography (PET/CT) scan
6. Left ventricular ejection fraction (LVEF) >=50%, as determined on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)

Exclusion criteria 6

1. Contraindication to any of the individual components of R-CHOP, including prior receipt of anthracyclines, history of severe allergic or anaphylactic reactions to murine monoclonal antibodies, or known sensitivity or allergy to murine products
2. Prior treatment for indolent lymphoma
3. Prior solid organ or allogeneic stem cell transplant
4. Positive SARS-CoV-2 test within 7 days prior to enrollment. Rapid antigen test result is also acceptable
5. Prior therapy for DLBCL and high-grade B-cell lymphoma (HGBCL) with the exception of palliative, short-term treatment with corticosteroids
6. Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 months after the final dose of R-CHOP, 3 months after the final dose of tocilizumab (if applicable), or 2 months after the final dose of glofitamab

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. EOT CR rate, as determined by the investigator according to the 2014 Lugano Response Criteria for Malignant Lymphoma

Secondary endpoints 10

1. 1. ORR at the EOT, as determined by the investigator according to the 2014 Lugano Response Criteria
2. 2. PFS, as determined by the investigator according to the 2014 Lugano Response Criteria or death due to any cause, whichever occurs first
3. 3. OS
4. 4. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
5. 5. Tolerability, as assessed by dose modifications, dose intensity, and study treatment discontinuation because of adverse events
6. 6. Serum concentrations of glofitamab at specified timepoints
7. 7. Serum trough concentrations of glofitamab at specified timepoints
8. 8. Maximum concentration (Cmax) of glofitamab at specified timepoints
9. 9. Area under the concentration–time curve (AUC) of glofitamab at specified timepoints
10. 10. Relationship between ADA status and efficacy, safety, or PK endpoints

Investigational products

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

Test 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

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

5 EU/EEA countries · 10 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 6 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