E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse Large B-Cell Lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of cell that is responsible for producing antibodies. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012818 |
E.1.2 | Term | Diffuse large B-cell lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• 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 |
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E.2.2 | Secondary objectives of the trial |
• 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 • To evaluate the safety of glofitamab in combination with R-CHOP in ctDNA high-risk participants with DLBCL • To characterize the serum pharmacokinetics (PK) profile of glofitamab in combination with R-CHOP • To evaluate potential effects of anti-drug antibodies (ADAs) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age >=18 years at the time of signing Informed Consent Form • Previously untreated patients with CD20-positive DLBCL, including one of the following diagnoses made according to the 2016 World Health Organization (WHO) classification of lymphoid neoplasms o DLBCL, not otherwise specified, including GCB and ABC/non-GCB types as well as double-expressor lymphoma (coexpression of MYC and BCL2) o High-grade B-cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 translocations o Patients with de novo transformed follicular lymphoma (patients with discordant bone marrow involvement, i.e., evidence of low-grade histology in bone marrow) may be considered after discussion with the Medical Monitor • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0–2 • International Prognostic Index (IPI): 1-5 • Life expectancy of >=6 months • 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 • At least one bi-dimensionally fluorodeoxyglucose (FDG)-avid measurable lymphoma lesion on positron emission tomography/computed tomography (PET/CT) scan • Left ventricular ejection fraction (LVEF) >=50%, as determined on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO) • Negative HIV test at screening, with the following exception: o Patients with a positive HIV test at screening are eligible provided that, prior to enrollment, they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count ³ >= 200/µL, and have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months • Adequate hematopoietic function For patients enrolled in France: - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing within 48 hours before study treatment administration at each treatment cycle - Vaccination status in line with French National guidelines/recommendations [COSV, National Agency for AIDS Research (ANRS), MIE] • Contraception use Additional Inclusion Criterion for ctDNA High-Risk Participants • Plasma sample evaluated to be ctDNA high risk using the experimental AOA-NHL Test, defined as <2-log fold reduction in ctDNA levels between Day 1 of Cycle 1 and Day 1 of Cycle 2 by central laboratory assessment |
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E.4 | Principal exclusion criteria |
• Current diagnosis of B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma (gray-zone lymphoma), primary mediastinal (thymic) large B-cell lymphoma, T cell/ histiocyte-rich large B-cell lymphoma, Burkitt lymphoma, central nervous system (CNS) lymphoma (primary or secondary involvement), primary effusion DLBCL, and primary cutaneous DLBCL • 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 • Prior treatment for indolent lymphoma • Prior solid organ or allogeneic stem cell transplant •Positive SARS-CoV-2 test within 7 days prior to enrollment. Rapid antigen test result is also acceptable • Prior therapy for DLBCL and high-grade B-cell lymphoma (HGBCL) with the exception of palliative, short-term treatment with corticosteroids • 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. EOT CR rate, as determined by the investigator according to the 2014 Lugano Response Criteria for Malignant Lymphoma |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 34 months |
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E.5.2 | Secondary end point(s) |
1. ORR at the EOT, as determined by the investigator according to the 2014 Lugano Response Criteria 2. PFS, as determined by the investigator according to the 2014 Lugano Response Criteria or death due to any cause, whichever occurs first 3. OS 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. Tolerability, as assessed by dose modifications, dose intensity, and study treatment discontinuation because of adverse events 6. Serum concentrations of glofitamab at specified timepoints 7. Serum trough concentrations of glofitamab at specified timepoints 8. Maximum concentration (Cmax) of glofitamab at specified timepoints 9. Area under the concentration–time curve (AUC) of glofitamab at specified timepoints 10. Relationship between ADA status and efficacy, safety, or PK endpoints |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3. Up to approximately 34 months 4-5. Up to 90 days after the final dose of study treatment 6-10. During treatment (up to approximately 10 months) and at treatment completion/discontinuation visit |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
Denmark |
France |
Netherlands |
Poland |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 7 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 9 |