A Study to Evaluate Efficacy and Safety of Mosunetuzumab in Combination with Lenalidomide in Comparison to Rituximab in Combination with Lenalidomide in Patients with Follicular Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Nov 2021 → ongoing

Decision date (initial)

2024-12-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche Ltd

External identifiers

EU CT number

2023-505807-21-00

EudraCT number

2020-005239-53

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Others

Arm A and Arm B: 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 C: The primary efficacy objective for the non-randomized single arm extension is to evaluate the efficacy of M + Len based on Objective response rate (ORR) as determined by the independent review committee (IRC)

Secondary objectives 8

1. Arm A and Arm B: 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
2. Arm A and Arm B: To evaluate the safety and tolerability of M+Len compared with R+Len
3. Arm A and Arm B: To characterize the pharmacokinetic (PK) profile of M+Len and R+Len
4. Arm A and Arm B: To evaluate the immune response to mosunetuzumab and rituximab
5. Arm C: Efficacy objective for the non-randomized single arm extension is to evaluate the efficacy of M + Len
6. Arm C: The safety objective for the non-randomized single arm extension is to evaluate the safety of M + Len
7. Arm C: To characterize the pharmacokinetic (PK) profile of M+Len
8. Arm C: To evaluate the immune response to mosunetuzumab

Conditions and MedDRA coding

Relapsed/refractory follicular lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically documented CD20 + follicular lymphoma (FL) (Grades 1-3a)
2. Requiring systemic therapy assessed by investigator based on tumor size and/or Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
3. Received at least one prior systemic lymphoma therapy, which included prior immunotherapy or chemoimmunotherapy
4. Availability of a representative tumor specimen and the corresponding pathology report at the time of relapse/persistence for confirmation of the diagnosis of FL
5. Agreement to comply with all local requirements of the lenalidomide risk minimization plan, which includes the global pregnancy prevention program
6. Adequate hematologic and organ function

Exclusion criteria 6

1. Any history of Grade 3b FL and transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL or transformed FL)
2. 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
3. Documented refractoriness to lenalidomide, defined as no response within 6 months of therapy
4. Positive SARS-CoV-2 test within 7 days prior to enrollment.
5. Known or suspected history of central nervous system (CNS) lymphoma or leptomeningeal infiltration, HLH (hemophagocytic lymphohistiocytosis) and progressive multifocal leukoencephalopathy (PML)
6. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Arm A and Arm B : 1. Progression-free survival as determined by the IRC with use of the 2014 Lugano Response Criteria or death from any cause in the intent-to-treat (ITT) population
2. Arm C : 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

Secondary endpoints 27

1. 1. Arm A and Arm B: Progression-free survival as determined by the investigator in the ITT population. Arm C: Progression-free survival as determined by the investigator and IRC in the ITT population.
2. 2. Arm A, Arm B and Arm C: Complete response rate in the ITT population as determined by the IRC and investigator
3. 3. Arm A, Arm B and Arm C: Objective response rate in the ITT population as determined by the IRC and investigator
4. 4. Arm A, Arm B and Arm C: Overall survival in the ITT population
5. 5. Arm A, Arm B and Arm C: Duration of objective response (DOR)
6. 6. Arm A, Arm B and Arm C: Duration of CR
7. 7. Arm A, Arm B and Arm C: Time to deterioration in physical functioning as measured by the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)
8. 8. Arm A, Arm B and Arm C: Time to deterioration in fatigue, as measured by the EORTC QLQC30
9. 9. Arm A, Arm B and Arm C: Time to deterioration in lymphoma symptoms, as measured by the Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS)
10. 10. Arm A, Arm B and Arm C : Time to new anti-lymphoma treatment (TTNALT), defined as the time from randomization to the first documented administration of a new anti-lymphoma treatment
11. 11. Arm A, Arm B and Arm C: 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
12. 12. Arm A, Arm B and Arm C: Change from baseline in targeted vital signs
13. 13. Arm A, Arm B and Arm C: Change from baseline in targeted clinical laboratory test results
14. 14. Arm A, Arm B and Arm C: Tolerability, as assessed by dose interruptions, dose reductions, and dose intensity, and study treatment discontinuation because of adverse events
15. 15. Arm A, Arm B and Arm C: Minimum observed concentration (Cmin) of Mosunetuzumab
16. 16. Arm A, Arm B and Arm C: Cmin of Lenalidomide
17. 17. Arm A, Arm B and Arm C: Maximum observed concentration (Cmax) of Mosunetuzumab
18. 18. Arm A, Arm B and Arm C: Cmax of Lenalidomide
19. 19. Arm A, Arm B and Arm C: Area under the concentration-time curve (AUC) of Mosunetuzumab
20. 20. Arm A, Arm B and Arm C: AUC of Lenalidomide
21. 21. Arm A, Arm B and Arm C: Prevalence of anti-drug antibodies (ADAs) against mosunetuzumab at baseline
22. 22. Arm A and Arm B: Prevalence of ADAs against rituximab at baseline
23. 23. Arm A, Arm B and Arm C: Incidence of ADAs against mosunetuzumab during the study
24. 24. Arm A and Arm B: Incidence of ADAs against rituximab during the study
25. 25. Arm A and Arm B: Cmin of Rituximab
26. 26. Arm A and Arm B: Cmax of Rituximab
27. 27. Arm A and Arm B: AUC of Rituximab

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 8

Locations

5 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 37 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications