| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed/refractory follicular lymphoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Follicular lymphoma is a cancer that affects white blood cells called lymphocytes. The term relapsed or refractory indicates disease that grows again or does not respond to the treatment. |
|
| 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 | 10016906 |
| E.1.2 | Term | Follicle centre lymphoma, follicular grade I, II, III refractory |
| 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 | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
• To evaluate the efficacy of mosunetuzumab in combination with lenalidomide (M+Len) compared with rituximab in combination with lenalidomide (R+Len) based on progression-free survival as determined by the independent review committee (IRC) (Arm A and B)
• To evaluate the efficacy of M+Len on the basis of objective response rate [For Non-Randomized,. Single Arm Extension (Arm C)]
|
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of M+Len compared with R+Len based on progression-free survival as determined by the investigator, complete response rate as determined by the IRC and investigator, objective response rate as determined by the IRC and investigator, overall survival, duration of objective response, duration of complete response (CR), time to deterioration in physical functioning and fatigue and time to deterioration in lymphoma symptoms, time to next anti-lymphoma treatment (Arm A, B and C)
• To evaluate the safety of M+Len compared with R+Len (Arm A, B and C)
• To characterize the pharmacokinetic (PK) profile of M+Len and R+Len (Arm A, B and C)
• To evaluate the immune response to mosunetuzumab and rituximab (Arm A, B and C)
|
|
| 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
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
Histologically documented CD20 + follicular lymphoma (FL) (Grades 1-3a)
Requiring systemic therapy assessed by investigator based on tumor size and/or Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
Received at least one prior systemic lymphoma therapy, which included prior immunotherapy or chemoimmunotherapy
Availability of a representative tumor specimen and the corresponding pathology report at the time of relapse/persistence for confirmation of the diagnosis of FL
Adequate hematologic function without growth factors or blood product transfusion within 14 days of first dose of study drug administration
Normal laboratory values
Negative HIV test at screening
Agreement to comply with all local requirements of the lenalidomide risk minimization plan, which includes the global pregnancy prevention program
Women of childbearing potential must agree to remain abstinent (refrain
from heterosexual intercourse) or use 2 adequate methods of contraception during the treatment period (including periods of
treatment interruption), and for at least 28 days after the final dose of lenalidomide, 3 months after the final dose of tocilizumab (if applicable),
mosunetuzumab, and 12 months after the final dose of rituximab
Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain
from donating sperm during the treatment period and for at least 28
days after the final dose of lenalidomide, 3 months after the final dose of
tocilizumab (if applicable) and 12 months after the final dose of rituximab
For patients enrolled in the extended China enrollment phase at National
Medical Products Administration (NMPA)-recognized sites: current resident of mainland China, Hong Kong, or Taiwan, and of Chinese
ancestry
|
|
| E.4 | Principal exclusion criteria |
Any history of Grade 3b FL
Any history of disease transformation and/or diffuse large B-cell lymphoma (DLBCL)
Documented refractoriness to lenalidomide, defined as no response (partial response or complete response) or relapse within 6 months of therapy
Positive SARS-CoV-2 test within 7 days prior to enrollment. Rapid antigen test result is also acceptable
Active or history of central nervous system (CNS) lymphoma or leptomeningeal infiltration
Prior standard or investigational anti-cancer therapy
Clinically significant toxicity (other than alopecia) from prior treatment that has not resolved to Grade <=1 (per National Cancer Institute Common Toxicity Criteria for Adverse Events Version 5.0 [NCI CTCAE, v5.0]) prior to Day 1 of Cycle 1
Treatment with systemic immunosuppressive medications within 2 weeks prior to Day 1 of Cycle 1
History of solid organ transplantation
History of severe allergic or anaphylactic reaction to humanized, chimeric or murine MAbs
Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary (CHO) cells or any component of the mosunetuzumab, lenalidomide, or thalidomide formulation, including mannitol
History of erythema multiforme, Grade >=3 rash, or blistering following prior treatment with immunomodulatory derivatives
History of interstitial lung disease (ILD), drug-induced pneumonitis, and autoimmune pneumonitis
Known active bacterial, viral, fungal, or other infection, or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1
Known or suspected chronic active Epstein-Barr virus (EBV) infection
Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
Active Hepatitis B or C infection
Known history of human immunodeficiency virus (HIV) positive status
History of progressive multifocal leukoencephalopathy (PML)
Administration of a live, attenuated vaccine within 4 weeks before first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study
Other malignancy that could affect compliance with the protocol or interpretation of results
Active autoimmune disease requiring treatment
History of autoimmune disease
Prior allogeneic stem cell transplant (SCT)
Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results,
including, but not limited to, significant cardiovascular disease or significant pulmonary disease
Major surgical procedure other than for diagnosis within 28 days prior to
Day 1 of Cycle 1 or anticipation of a major surgical procedure during the course of the study
Pregnant or lactating or intending to become pregnant during the study
Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Progression-free survival as determined by the IRC with use of the2014 Lugano Response Criteria or death from any cause in the intent-to-treat (ITT) population
2. Objective response rate as defined as the proportion of patients whose best overall response is a PR or a CR during the study, as determined by the IRC (For Non-Randomized, Single Arm Extension) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 1-2. Up to approximately 8.5 years |
|
| E.5.2 | Secondary end point(s) |
• Progression-free survival as determined by the investigator in the ITT population
• Complete response rate in the ITT population as determined by the IRC and investigator
• Objective response rate in the ITT population as determined by the IRC and investigator
• Overall survival in the ITT population
• Duration of objective response (DOR)
• Duration of CR
• Time to deterioration in physical functioning and fatigue, as measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)
• Time to deterioration in lymphoma symptoms, as measured by the Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS)
• Time to next anti-lymphoma treatment (TTNALT), defined as the time from randomization to the first documented administration of a new
anti-lymphoma treatment.
• Incidence and severity of adverse events, with severity determined according to the NCI CTCAE, v5.0, including cytokine release syndrome (CRS), with severity determined according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS grading criteria
• Change from baseline in targeted vital signs
• Change from baseline in targeted clinical laboratory test results
• Tolerability, as assessed by dose interruptions, dose reductions, and dose intensity, and study treatment discontinuation because of adverse events
• Minimum observed concentration (Cmin) of Mosunetuzumab
• Cmin of Lenalidomide
• Maximum observed concentration (Cmax) of Mosunetuzumab
• Cmax of Lenalidomide
• Area under the concentration-time curve (AUC) of Mosunetuzumab
• AUC of Lenalidomide
• Prevalence of anti-drug antibodies (ADAs) against mosunetuzumab at baseline
• Prevalence of ADAs against rituximab at baseline
• Incidence of ADAs against mosunetuzumab during the study
• Incidence of ADAs against rituximab during the study
• Cmin of Rituximab
• Cmax of Rituximab
• AUC of Rituximab
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-10. Up to approximately 8.5 years
11-12. Baseline to 8.5 years
13. Up to approximately 8.5 years
14. Days 1, 8 and 15 of Cycle 1, Day 1 of Cycles 2 to 12
15. Day 1 of Cycles 2 to 11
16. Days 1, 8 and 15 of Cycle 1, Day 1 of Cycles 2 to 12
17. Day 1 of Cycles 2 to 11
18. Days 1, 8 and 15 of Cycle 1, Day 1 of Cycles 2 to 12
19. Day 1 of Cycles 2 to 11
20-21 . At Baseline
22-23. Up to approximately 8.5 years
24-26. Days 1, 8 and 15 of Cycle 1, Day 1 of Cycles 2 to 11 |
|
| 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 | 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 | 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| 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 | 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 15 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 64 |
| 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 |
| Ukraine |
| Taiwan |
| Australia |
| Brazil |
| China |
| Japan |
| Korea, Republic of |
| Russian Federation |
| Turkey |
| United Kingdom |
| United States |
| France |
| Germany |
| Italy |
| Poland |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
The end of this study is defined as the date when the last patient, last visit, occurs (i.e., last
patient in the global and extended China enrollment phases combined) or the date at which the
last data point required for statistical analysis or safety follow-up is received from the last patient
(global and extended China enrollment phases combined), whichever occurs later.
In addition, the Sponsor may decide to terminate the study at any time. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 8 |
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