A Study to Evaluate the Efficacy and Safety of Glofitamab in Combination with Gemcitabine Plus Oxaliplatin Versus Rituximab in Combination with Gemcitabine Plus Oxaliplatin in Patients with Relapsed/Refractory 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

25 Mar 2021 → ongoing

Decision date (initial)

2024-06-21

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

2023-506899-27-00

EudraCT number

2020-001021-31

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Pharmacokinetic, Safety

To evaluate the efficacy of glofitamab (Glofit)- gemcitabine plus oxaliplatin (GemOx) compared with rituximab in combination with gemcitabine and oxaliplatin (R-GemOx) on the basis of overall survival

Secondary objectives 5

1. To evaluate the efficacy of Glofit-GemOx compared with R-GemOx on the basis of progression-free survival, complete response rate, objective response rate, duration of objective response, duration of complete response, time to deterioration in physical functioning and fatigue
2. To evaluate the safety and tolerability of Glofit-GemOx compared with R-GemOx
3. To evaluate the pharmacokinetics of Glofit when administered as a component of Glofit-GemOx
4. To evaluate the pharmacokinetics of obinutuzumab
5. To evaluate the immune response to Glofit-GemOx

Conditions and MedDRA coding

Relapsed or refractory diffuse large B-cell lymphoma

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. Life expectancy >= 12 weeks
2. Histologically confirmed diffuse large B-cell lymphoma, not otherwise specified (NOS)
3. Relapsed/refractory disease
4. At least one (≥ 1) line of prior systemic therapy
5. Patients who have failed only one prior line of therapy must not be a candidate for high-dose chemotherapy followed by autologous stem cell transplant
6. At least one bi-dimensionally measurable (>= 1.5 cm) nodal lesion, or one bi-dimensionally measurable (=> 1 cm) extranodal lesion, as measured on computed tomography (CT) scan

Exclusion criteria 6

1. Patient has failed only one prior line of therapy and is a candidate for stem cell transplantation
2. Contraindication to Obinutuzumab, rituximab, gemcitabine or oxaliplatin, or tocilizumab
3. History of transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL)
4. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B-cell lymphoma NOS, as defined by 2016 WHO guidelines
5. Primary mediastinal B-cell lymphoma
6. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Overall Survival

Secondary endpoints 16

1. 1. Progression-Free Survival by Independent review committee (IRC) and Investigator
2. 2. Complete response rate by IRC and Investigator
3. 3. Objective response rate by IRC and Investigator
4. 4. Duration of objective response
5. 5. Duration of complete response
6. 6. Time to deterioration in physical functioning and fatigue, as measured by the European Organisation for Research and Treatment of Cancer Quality of Life−Core 30 Questionnaire (EORTC QLQ-C30) and in lymphoma symptoms, as measured by the Functional Assessment of Cancer Therapy−Lymphoma subscale (FACT-Lym LymS)
7. 7. Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0, including cytokine-release syndrome (CRS), with severity determined according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS grading criteria
8. 8. Change from baseline in targeted vital signs
9. 9. Change from baseline in targeted clinical laboratory test results
10. 10. Tolerability, as assessed by dose interruptions, dose reductions, and dose intensity, and study treatment discontinuation because of adverse events
11. 11. Minimum serum concentration of glofitamab
12. 12. Maximum serum concentration of glofitamab
13. 13. Area under the concentration-time curve (AUC) for serum concentration−time profile of glofitamab estimated using a population-PK model
14. 14. Minimum serum concentration of obinutuzumab
15. 15. Maximum serum concentration of obinutuzumab
16. 16. Prevalence of anti-drug antibodies (ADAs) against glofitamab at baseline and incidence of ADAs during the study

Investigational products

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

Test 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 16

Locations

6 EU/EEA countries · 17 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 52 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