E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
B-Cell Non-Hodgkin Lymphoma (B-cell NHL) |
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E.1.1.1 | Medical condition in easily understood language |
B-cell NHL is cancer that originates in your lymphatic system, the disease-fighting network spread throughout body. In NHL, tumors develop from B-lymphocytes -a type of white blood 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 | 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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase Ib
Mosunetuzumab + cyclophosphamide, doxorubicin, vincristine, prednisone (M-CHOP):
•To evaluate safety, tolerability of M-CHOP in patients with relapsed or refractory (R/R) B-cell NHL including estimation of the maximum tolerated dose (MTD), determination of recommended Phase II dose (RP2D), and characterization of dose-limiting toxicities (DLTs)
Mosunetuzumab + cyclophosphamide, doxorubicin, prednisone, polatuzumab vedotin (M-CHP-pola):
•To evaluate the safety and tolerability of M CHP-pola in patients with relapsing/refractory (R/R) B-cell NHL, including estimation of the MTD, determination of RP2D, and characterization of DLTs
Phase II
To evaluate
•Efficacy of M-CHP-pola compared with rituximab (R)-CHP-pola in patients with previously untreated diffuse large B-cell lymphoma (DLBCL)
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E.2.2 | Secondary objectives of the trial |
Phase Ib
To evaluate
•Pharmacokinetics (PK) of mosunetuzumab when administered in combination with CHOP/CHP-pola, polatuzumab vedotin when administered in combination with mosunetuzumab, CHP
•Relationship between serum PK, safety, biomarkers, efficacy
•Preliminary assessment of anti-tumor activity of M-CHOP and M-CHP-pola
Phase II
•Efficacy of M-CHP-pola compared with R-CHP-pola in patients with previously untreated DLBCL
•Efficacy of M-CHOP in patients with previously untreated DLBCL
Phase Ib and II
•Immune response to mosunetuzumab, polatuzumab vedotin and potential effect of mosunetuzumab, polatuzumab vedotin anti-drug antibody (ADA) incidence on relevant clinical outcomes
•Safety, tolerability of M-CHP-pola compared with R-CHP-pola, M-CHOP
•PK of mosunetuzumab when administered by IV infusion with CHOP, CHP-pola, polatuzumab vedotin when administered by IV infusion with mosunetuzumab, CHP |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Phase Ib and Phase II
- Age >= 18 years
- At least one bi-dimensionally measurable nodal lesion
- Life expectancy of at least 24 weeks
- Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
- Left ventricular ejection fraction defined by multiple-gated acquisition scan or echocardiogram within the institutional limits of normal
- Adequate hematologic function
- Serum creatinine <= ULN; or estimated creatinine clearance >= 50 mL/min by Cockroft-Gault method or other institutional standard methods
- Contraception use
Phase Ib
- Histologically confirmed B-cell NHL according to WHO 2016 classification
- R/R B-cell NHL after at least one prior systemic lymphoma therapy
- Treatment with at least one prior CD20-directed therapy
- Group B only: no prior treatment with polatuzumab vedotin
Phase II
- Previously untreated, histologically confirmed DLBCL according to WHO 2016 classification
- International Prognostic Index score of 2-5 |
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E.4 | Principal exclusion criteria |
- Pregnant or breastfeeding, or intending to become pregnant during the study
- Prior treatment with mosunetuzumab and prior stem-cell transplant
- Contraindication to receive full dose of any of the individual components
- Current Grade >1 peripheral neuropathy
- Received systemic immunosuppressive medications
- Current or past history of central nervous system (CNS) lymphoma
- Current or past history of CNS disease
- Known or suspected history of hemophagocytic lymphohistiocytosis
- Prior radiotherapy to the mediastinal/pericardial region
- History of other malignancy
- Recent major surgery
Phase Ib
- Prior treatment with >250 mg/m2 doxorubicin (or equivalent anthracycline dose)
- Prior treatment with chemotherapy, immunotherapy, and biologic therapy within a specified period
- Prior treatment with radiotherapy within a specified period
- Adverse events from prior anti-cancer therapy resolved to <= Grade 1
Phase II
- Patients with transformed lymphoma
- Prior therapy for B-cell NHL |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase Ib
1.Occurrence and severity of adverse events
2.Occurrence of DLT with severity determined according to NCI CTCAE v5.0
3.Change from baseline in targeted vital signs
4.Change from baseline in targeted clinical laboratory test results
5.Number of cycles received and dose density and intensity
Phase II
6.Complete response (CR) rate at the time of primary response assessment (PRA) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 60 months
2. C1D1 through C1D21
3-4. From baseline to 60 months
5. Up to 60 weeks
6. Up to 60 months |
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E.5.2 | Secondary end point(s) |
1.Maximum serum concentration (Cmax) of mosunetuzumab
2.Minimum serum concentration (Cmin) of mosunetuzumab
3.Total exposure (AUC) of mosunetuzumab
4.Clearance of mosunetuzumab
5.Volume of distribution of mosunetuzumab at steady state
6.Relationship between serum pharmacokinetics and safety, biomarkers, or efficacy endpoints
7.Complete response rate at the time of primary response assessment
8.Best overall response rate and ORR
9.Duration of response
10.Progression free survival
11.Progression free survival at 1 year
12.Event-free survival
13.Time to deterioration
14.Occurrence and severity of adverse events including DLTs
15.Incidence of ADAs to mosunetuzumab
16.Incidence of ADAs to polatuzumab vedotin
17.Relationship between ADAs and PK, safety, efficacy, and biomarkers
18.Occurrence and severity of adverse events
19.Change from baseline in targeted vital signs
20.Change from baseline in targeted clinical laboratory test results and clinical assessments
21.Number of cycles received and dose density and intensity |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-6. Up to 60 weeks
7-10. Up to 60 months
11. At 1 year
12-13. Up to 60 months
14. C1D1 through C1D21
15-16. Up to 60 weeks
17-19. Up to 60 months
20. From baseline (-14 days) to up to 60 months
21. Up to 60 weeks |
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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 | Yes |
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 | 3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 |
Austria |
France |
Korea, Republic of |
Poland |
Spain |
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. |
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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 |