| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed or Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (NHL) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Non-Hodgkin Lymphoma is a cancer of the lymphatic system. It develops when the body makes abnormal B lymphocytes. |
|
| 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 | 24.0 |
| 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 | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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) |
|
| 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 1b
•To evaluate the safety of mosunetuzumab subcutaneous (SC) in combination with tiragolumab intravenous (IV) with or without atezolizumab IV, including evaluation of the tolerability of the dosing schedule and dose, and characterization of dose limiting toxicities (DLTs).
Phase 2
•To evaluate the efficacy of mosunetuzumab SC in combination with tiragolumab IV in participants with R/R follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), and mosunetuzumab SC in combination with tiragolumab IV and atezolizumab IV in participants with R/R FL and R/R DLBCL.
|
|
| E.2.2 | Secondary objectives of the trial |
Phase 1b
•To evaluate the preliminary efficacy of mosunetuzumab SC in combination with tiragolumab with or without atezolizumab IV
Phase 2
•To evaluate the efficacy of mosunetuzumab SC in combination with tiragolumab IV in participants with R/R follicular lymphoma (FL) and
diffuse large B cell lymphoma (DLBCL), and mosunetuzumab SC in combination with tiragolumab IV and atezolizumab IV in participants
with R/R FL.
Phase 2 - secondary safety objectives
•To evaluate the efficacy and safety of mosunetuzumab SC in combination with tiragolumab IV in participants with R/R FL and DLBCL,
and mosunetuzumab SC in combination with tiragolumab IV and atezolizumab IV in participants with R/R FL
Phase 1b and 2
•To characterize the PK profile of mosunetuzumab SC in combination with tiragolumab IV
•To characterize the PK profile of mosunetuzumab SC in combination with tiragolumab IV and atezolizumab IV
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Age >= 18 years
- Participants who have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- Participants who have a life expectancy of at least 12 weeks that has relapsed or failed to respond to at least two prior systemic treatment regimens and for which no suitable therapy of curative intent or higher priority exists (e.g., standard chemotherapy, ASCT, CAR T cells).
- Participants who have histologically documented FL or DLBCL that expresses CD20 as determined by the local laboratory.
- Participants who have at least one bi-dimensionally measurable (>1.5 cm) nodal lesion, or at least one bi-dimensionally measurable (>1.0 cm) extranodal lesion
- Participants who have confirmed availability of a tumor tissue
- Participants with FL for whom a bone marrow biopsy and aspirate can be collected
- Participants with adequate hematologic and organ function
|
|
| E.4 | Principal exclusion criteria |
Participants who have received any of the following treatments prior to
study entry:
o Treatment with mosunetuzumab or other CD20/CD3-directed bispecific antibodies
o Treatment with tiragolumab or other anti- T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domains agent
o Allogeneic stem Cell Transplant (SCT)
o Solid organ transplantation
- Participants who received any of the following treatments, whether investigational or approved, within the respective time periods prior to
initiation of study treatment:
o Radiotherapy within 2 weeks prior to the first dose of study treatment If participants have received radiotherapy within 4 weeks prior to the first study treatment administration, participants must have at least one measurable lesion outside of the radiation field.
o Autologous SCT within 100 days prior to first study treatment
o Chimeric antigen receptor T-cell therapy within 30 days before first study treatment
o Use of monoclonal antibodies or antibody-drug conjugates for the treatment of lymphoma, within 4 weeks prior to first study treatment
o Use of radioimmunoconjugates within 12 weeks prior to first study treatment
o Systemic immunosuppressive medications within 2 weeks prior to
first dose of study treatment
o Any other anti-cancer therapy, whether investigational or approved
o The Medical Monitor should be informed of any prior cancer immunotherapy not explicitly described in this protocol
- Participants who received a live, attenuated vaccine within 4 weeks before first dose of study treatment, or in whom it is anticipated that
such a live attenuated vaccine will be required during the study period or within 5 months after the final dose of study treatment
- Participants with aggressive NHL who are currently eligible for autologous SCT
- Participants with current or past history of CNS lymphoma or
leptomeningeal infiltration
- Participants with a history of severe allergic or anaphylactic reactions
to humanized or murine monoclonal antibody therapy
- Participants with a contraindication to atezolizumab (specific to Arm
2 of the study ) or tocilizumab
- Participants in whom clinically significant toxicities from prior treatment have not resolved to Grade <= 1 (per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE]
v5.0) prior to the first study drug administration
- Participants with treatment-emergent immune-mediated adverse events associated with prior immunotherapeutic agents
- Participants with evidence of any significant, concomitant disease that could affect compliance with the protocol or interpretation of results
- Participants who underwent recent major surgery within 4 weeks prior to first study treatment administration |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Phase Ib
1.Incidence and severity of adverse events, including DLTs, with severity
determined according to NCI CTCAE v5.0; for CRS, severity determined according to American Society for Transplantation and
Cellular Therapy cytokine-release syndrome consensus grading criteria
Phase 2
2.Best objective response rate as determined by the investigator using Lugano 2014 criteria |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Until 90 days after the final dose of study treatment
2. Up to 36 Months
|
|
| E.5.2 | Secondary end point(s) |
Phase Ib
1. Best objective response rate*
2. Best complete response rate*
3. Duration of response*
Phase 2
4. Best complete response rate*
5. Duration of response*
6. Progression free survival*
7. Event-free survival*
8. Overall survival
9. Occurrence and severity of adverse events, with severity determined
according to NCI CTCAE v5.0. For CRS, severity determined according to
the ASTCT CRS Consensus Grading criteria
*as determined by the investigator using Lugano 2014 criteria |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-8. Up to 36 Months
9. Until 90 days after the final dose of study treatment
|
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| other exploratory objectives outside of pharmacokinetic (i.e. immunogenicity and biomarkers) |
|
| 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 |
|
| 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 | Yes |
| 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 | 2 |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 2 |
| 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 |
| Australia |
| Canada |
| New Zealand |
| United States |
| Germany |
| Belgium |
| United Kingdom |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| 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 | 4 |
| 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 |
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