A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of Glofitamab in Monotherapy and in Combination with Chemoimmunotherapy in Pediatric and Young Adult Participants with Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Health Care [N] - Environment and Public Health [N06], Diseases [C] - Neoplasms [C04]

Trial duration

4 Nov 2022 → ongoing

Decision date (initial)

2025-07-29

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

2023-504264-41-00

EudraCT number

2021-006326-48

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Pharmacokinetic, Safety

To evaluate the efficacy of glofitamab in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) chemoimmunotherapy, as assessed by the investigator based on achievement of a complete response (CR) To evaluate the safety and tolerability of glofitamab in combination with R-ICE chemoimmunotherapy To determine the pharmacokinetics of glofitamab alone and in combination with R-ICE chemoimmunotherapy

Secondary objectives 4

1. To evaluate the anti-tumor activity of glofitamab in combination with R-ICE chemoimmunotherapy and glofitamab monotherapy
2. To evaluate the safety and tolerability of glofitamab monotherapy
3. To determine the pharmacokinetics of obinutuzumab and rituximab
4. To evaluate the immune response to glofitamab

Conditions and MedDRA coding

CD20 positive B-Cell Non-Hodgkin Lymphoma (NHL)

Study design 1 period

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002648-PIP01-19

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age 6 months to <18 years at the time of signing Informed Consent for Cohort A Part 1 and Cohort B of the study, and age 6 months to < 30 years old at the time of signing Informed Consent for Cohort A Part 2 of the study Cohort A Part 2–18 up to < 30 years old, is restricted to young adults with first relapsed or refractory (R/R) aggressive mature B-NHL for whom no alternative standard-of-care treatment is available
2. Histologically re-confirmed diagnosis, via tissue biopsy, or bone marrow aspirate, pleural effusion, or ascites, prior to study entry of aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) that expresses CD20 (reconfirmed by immunohistochemistry [IHC]), or flow cytometry if IHC is not possible including Burkitt lymphoma (BL), Burkitt leukemia (BAL) (mature B-cell leukemia fragment antigen-binding [FAB] L3), diffuse large B-cell lymphoma (DLBCL), and primary mediastinal large B-cell lymphoma (PMBCL), at the time of first relapsed or refractory (R/R) disease for Cohort A and second or greater R/R disease for Cohort B
3. Refractory or relapsed disease (i.e., prior treatment was ineffective or intolerable) following first-line standard-of-care chemoimmunotherapy for Cohort A and following at least two prior systemic chemoimmunotherapy regimens and who have exhausted all available established therapies for Cohort B Measurable disease, defined as – At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension or – Percentage of bone marrow involvement with lymphoma cells defined by cytomorphological analysis of bone marrow aspirates
4. Adequate performance status, as assessed according to the Lansky or Karnofsky Performance Status scales
5. Adequate bone marrow, liver and renal function
6. Negative test results for hepatitis B and hepatitis C viruses (HBV and HCV), human immunodeficiency virus (HIV) and severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2).

Exclusion criteria 6

1. Exclusion criteria applicable to both Cohorts A and B - Isolated CNS disease of mature B-NHL without systemic involvement, and primary central nervous system (CNS) lymphoma
2. Exclusion criteria applicable to Cohorts A only - Receipt of glofitamab prior to study enrollment
3. Exclusion criteria applicable to Cohort A only - Receipt of any R-ICE chemoimmunotherapy prior to study enrollment into Cohort A
4. Exclusion criteria applicable to Cohort A only - Receipt of more than one prior line of standard-of-care B-NHL chemoimmunotherapy
5. Exclusion criteria applicable to Cohort B only - Prior treatment with standard radiotherapy (within 2 weeks before Day 1 of Cycle 1), systemic chemotherapy and immunotherapeutic anticancer agents (within 4 weeks or five half-lives of the drug, before Day 1 of Cycle 1)
6. Exclusion criteria applicable to Cohort B only - Patients with uncontrolled CNS involvement

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Cohort A - Glofitamab Combination Therapy (glofitamab plus R-ICE chemoimmunotherapy) 1. Achievement of a complete response (CR) after up to three cycles of treatment as determined by the investigator according to the International Pediatric NHL Response Criteria for pediatric participants and Lugano Classification for young adult participants
2. Cohort A - Glofitamab Combination Therapy (glofitamab plus R-ICE chemoimmunotherapy) 2. Incidence, nature, frequency, severity, and timing of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE v5.0) (glofitamab plus R-ICE chemoimmunotherapy)
3. Cohort A - Glofitamab Combination Therapy (glofitamab plus R-ICE chemoimmunotherapy) 3. Change from baseline in physical findings, vital signs, clinical laboratory test results and electrocardiogram (ECG) parameters
4. 4. Pharmacokinetics (PK) parameters (as appropriate) and serum concentrations of glofitamab monotherapy at specified timepoints
5. 5. PK parameters (as appropriate) and serum concentrations of glofitamab in combination with R-ICE chemoimmunotherapy at specified timepoints

Secondary endpoints 7

1. 1. For glofitamab plus R-ICE chemoimmunotherapy: Objective response rate (ORR), Duration of complete response (DOCR), Progression-free survival (PFS) after enrollment, Event-free survival (EFS), Overall survival (OS) and percentage of patients who proceed to HSCT after up to three cycles of treatment
2. 2. For glofitamab monotherapy: ORR, Duration of response (DOR) and OS
3. Glofitamab monotherapy 3. Incidence, nature, frequency, severity, and timing of adverse events, with severity determined according to NCI CTCAE v5.0
4. Glofitamab monotherapy 4. Change from baseline in physical findings, vital signs, clinical laboratory test results and ECG parameters
5. 5. Serum concentrations of obinutuzumab at specified timepoints
6. 6. Serum concentrations of rituximab at specified timepoints
7. 7. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs against glofitamab during the study

Investigational products

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

Test 7

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 11

Locations

8 EU/EEA countries · 11 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 132 files

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

Application history

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