E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
B-cell non-Hodgkin lymphoma (NHL) |
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E.1.1.1 | Medical condition in easily understood language |
B-cell NHL, including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) as subtypes, is a type of cancer that forms in B-cells (a type of immune system cell) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067070 |
E.1.2 | Term | Follicular B-cell non-Hodgkin's lymphoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025320 |
E.1.2 | Term | Lymphomas non-Hodgkin's B-cell |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012820 |
E.1.2 | Term | Diffuse large B-cell lymphoma NOS |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012856 |
E.1.2 | Term | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) recurrent |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023768 |
E.1.2 | Term | Large cell immunoblastic lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) recurrent |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012857 |
E.1.2 | Term | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) refractory |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023769 |
E.1.2 | Term | Large cell immunoblastic lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) refractory |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Phase Ib
• To evaluate the safety and tolerability of mosunetuzumab (Mosun) + polatuzumab vedotin (Pola) in patients with relapsed or refractory (R/R) DLBCL or follicular lymphoma (FL), including estimation of maximum tolerated dose, determination of recommended Phase II dose (RP2D), characterization of dose-limiting toxicity (DLT)
• To make a preliminary assessment of the anti-tumor activity of Mosun + Pola
Phase II:
• To evaluate the efficacy of Mosun plus Pola in patients with R/R FL and R/R DLBCL based on complete response (CR) rate by positron emission tomography- computed tomography (PET-CT) at primary response assessment (PRA)
• To evaluate the efficacy of Mosun plus Pola compared with Pola plus bendamustine and rituximab in patients with R/R DLBCL based on CR
ate by PET-CT at PRA |
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E.2.2 | Secondary objectives of the trial |
Phase Ib and II
• Characterize the pharmacokinetics of Mosun as a single agent and when administered in combination with Pola
• Assess the incidence of anti-drug antibodies (ADAs) to Mosun and Pola Phase II
• To evaluate the efficacy of Mosun + Pola in R/R DLBCL and R/R FL
ased on CR rate by CT at PRA; objective response rate (ORR) at PRA; best ORR; duration of response (DOR); progression-free survival (PFS); event-free survival (EFS); overall survival (OS)
• To evaluate the efficacy of Mosun plus Pola compared with Pola plus bendamustine and rituximab in patients with R/R DLBCL based on CR rate by CT at PRA; ORR at PRA; best ORR; DOR; PFS; EFS; OS; time to deterioration of health-related quality of life |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 18 years
- Able to comply with the study protocol and procedures in the investigator’s judgment
- Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
- Life expectancy of at least 12 weeks
- Histologically confirmed FL or DLBCL
- Must have received at least one prior systemic treatment regimen containing an anti- cluster of differentiation 20 (CD20) - directed therapy for DLBCL or FL
- Adequate hepatic, hematologic and renal function
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E.4 | Principal exclusion criteria |
- Inability to comply with protocol-mandated hospitalization and activity restrictions
- Pregnant or lactating women
- Prior treatment with Mosun or other CD20-directed bispecific antibodies or with Pola
- Current > Grade 1 peripheral neuropathy
- Prior use of any monoclonal antibody, radioimmunoconjugate or antibody-drug conjugate chemotherapy, or other investigational anti-cancer agent within 4 weeks before first dose of study treatment
- Treatment with radiotherapy within 2 weeks prior to the first dose of study treatment
- Autologous stem-cell transplantation (SCT) within 100 days prior to first study treatment administration, or any prior allogeneic SCT or solid organ transplantation
- Prior treatment with chimeric antigen receptor -T therapy within 30 days before first study treatment administration
- Current or past history of central nervous system (CNS) lymphoma and of CNS disease
- Significant cardiovascular disease or pulmonary disease
- Recent major surgery within 4 weeks prior to first study treatment administration
- Hepatitis B or C or human immunodeficiency virus (HIV)
- Administration of a live, attenuated vaccine within 4 weeks before first dose of study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
- History of autoimmune disease (stable autoimmune diseases may be eligible)
- Systemic immunosuppressive medication within 2 weeks prior to study drug
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Occurrence and severity of adverse events, including DLTs (Phase Ib)
2. Change from baseline in targeted vital signs (Phase Ib),
3. Change from baseline in targeted clinical laboratory test results(Phase Ib)
4. CR rate at the time of primary response assessment (PRA) based on positron emission tomography (PET)- computed tomography (CT) scan, as determined by the IRC (Phase II)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-3. Up to 42 days from Cycle (C) 1 Day (D) 1
4. For patients receiving Mosun, at the completion of 8 cycles of Mosun; for patients randomized to receive Pola + bendamustine and rituximab, up to 7 weeks after completion of 6 cycles of therapy
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E.5.2 | Secondary end point(s) |
1. CR rate at the time of PRA based on PET-CT, as determined by the investigator
2. CR rate at the time of PRA based on CT only, as determined by the investigator and IRC
3. ORR at PRA based on PET-CT and CT only, as determined by the investigator and IRC
4. Best ORR on study based on PET-CT or CT only, as determined by the investigator and IRC
5. DOR, as determined by the investigator and IRC
6. PFS, as determined by the investigator and IRC
7. EFS as determined by the investigator and IRC
8. OS
9. Time to deterioration in European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire physical functioning and fatigue and in the Functional Assessment of Cancer Therapy- Lymphoma (subscale)
10. Maximum serum concentration (Cmax) for Mosun
11. Minimum serum concentration (Cmin) for Mosun
12. Total exposure area under the concentration-time curve (AUC) for Mosun
13. Clearance for Mosun
14. Volume of distribution for Mosun
15. Relationship between ADA status and efficacy, safety, pharmacokinetics, and biomarkers
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3. At the completion of 8 cycles of Mosun or up to 7 weeks after completion of 6 cycles of Pola + bendamustine and rituximab
4-9. Up to 60 months
10-15. At predose and postdose during treatment, at treatment completion/discontinuation and during follow-up, up to 15 months |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, immunogenicity, biomarkers |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 8 |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Canada |
Germany |
Israel |
United States |
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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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The end of this study is defined as the date when the last patient, last visit occurs, including survival follow-up visits conducted by telephone or on-site visit. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |