A Study Evaluating the Safety, Pharmacokinetics (what the body does to a drug), and Efficacy of Mosunetuzumab given subcutaneously (SC) or intravenously (IV) plus Lenalidomide (+Len) 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

28 Jul 2020 → ongoing

Decision date (initial)

2024-05-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-507236-20-00

EudraCT number

2019-004291-20

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy, Pharmacokinetic

Non-Randomized Stage R/R FL Cohort: To evaluate the maximum tolerated dose (MTD) and select the recommended Phase II dose (RP2D) of mosunetuzumab (Mosun) + lenalidomide (Len)
Non-Randomized Stage 1L FL Cohort: To evaluate the treatment efficacy of Mosun+Len by measuring response rate
Randomized Stage: To assess the pharmacokinetics non inferiority of the Mosun SC+Len regimen compared to the reference Mosun IV+Len regimen, each in combination with Len

Secondary objectives 4

1. Non-Randomized and Randomized Stages: To evaluate treatment efficacy by measuring response and long-term efficacy outcomes after treatment with Mosun + Len
2. Randomized Stage: To evaluate safety and tolerability of IV Mosun+Len and SC Mosun+Len
3. Non-Randomized Stage: To characterize the PK of Mosun when administered in combination with Len
4. Non-Randomized and Randomized Stages: To evaluate the immune response to Mosun when combined with Len

Conditions and MedDRA coding

Follicular Lymphoma (FL)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
2. R/R FL after treatment with at least one prior systemic lymphoma therapy which includes prior immunotherapy or chemoimmunotherapy
3. Previously untreated patients with FL must require systemic therapy assessed by investigator based on GELF criteria and have a Follicular Lymphoma International Prognostic Index (FLIPI) score of 2-5
4. Histologically documented FL of Grade 1, 2, or 3a, and that expresses CD20 as determined by the local laboratory
5. Fluorodeoxyglucose avid lymphoma (i.e., positron emission tomography (PET) positive lymphoma)
6. At least one bi dimensionally measurable nodal lesion (>1.5 cm in its largest dimension by PET- computed tomography (CT) scan), or at least one bi dimensionally measurable extranodal lesion (>1.0 cm in its largest dimension by PET-CT scan)

Exclusion criteria 6

1. Any history of Grade 3b FL
2. Any History of disease transformation and/or diffuse large B-cell lymphoma
3. Active or history of central nervous system lymphoma or leptomeningeal infiltration
4. Documented refractoriness to lenalidomide, defined as no response (PR or CR) within 6 months of therapy
5. Prior standard or investigational anti-cancer therapy as specified
6. Clinically significant toxicity (other than alopecia) from prior treatment that has not resolved to Grade <=2 prior to Day 1 of Cycle 1

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. 1. Non-randomized Stage: Dose-limiting toxicity
2. 2. Non-randomized Stage: Incidence, nature, and severity of physical findings and adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v5.0); for CRS, severity determined according to the American Society for Transplantation and Cellular Therapy (ASTCT) cytokine-release syndrome (CRS) grading criteria
3. 3. Non-randomized Stage : Change from baseline in targeted vital signs
4. 4. Non-randomized Stage : Change from baseline in targeted clinical laboratory test results
5. 5. Non-randomized Stage : Tolerability, as assessed by the incidence of dose interruptions, dose reductions and dose intensity, and treatment discontinuation not due to efficacy events
6. 6. ORR, defined as the proportion of patients whose best overall response is a PR or a CR during the study.
7. 7. Randomized stage: Cumulative Area under the concentration-time curve (AUC) over Cycles 1-3 (AUCC1-3)
8. 8. Randomized stage: Serum trough concentration at steady state, approximated by Cycle 4 (Ctrough, C4)

Secondary endpoints 15

1. 1. Non-randomized and Randomized stages : Complete response rate
2. 2. Non-randomized and Randomized stages : Objective response rate
3. 3. Non-randomized and Randomized stages : Duration of response
4. 4. Non-randomized and Randomized stages : Duration of complete response
5. 5. Non-randomized Stage : Minimum serum concentration (Cmin) of Mosun+ Len
6. 6. Non-randomized Stage : Maximum serum concentration (Cmax) of Mosun+ Len
7. 7. Randomized stage: Area under the concentration-time curve (AUC) of Mosun+ Len
8. 8. Non-randomized and Randomized stages: Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study
9. 9. Randomized stage: Incidence, nature, and severity of physical findings and adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v5.0); for CRS, severity determined according to the ASTCT CRS grading criteria
10. 10. Randomized stage: Change from baseline in targeted vital signs
11. 11. Randomized stage: Change from baseline in targeted clinical laboratory test results
12. 12. Randomized stage: Tolerability, as assessed by the incidence of dose interruptions, dose reductions and dose intensity, and treatment discontinuation not due to efficacy events
13. 13. Randomized stage: Cumulative AUC over Cycles 1-2 (AUCC1-2)
14. 14. Randomized stage: Serum trough concentration in Cycle 2 (Ctrough, C2)
15. 15. Randomized stage: AUC at steady state (AUCss)

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 12

Locations

2 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 12 files

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

Application history

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