Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Participants With Diffuse Large B-Cell Lymphoma Following First-Line Immunochemotherapy and as Monotherapy or in Combination With Polatuzumab Vedotin in Elderly/ Unfit Participants With Previously Untreated Diffuse Large B-Cell 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

2 Jul 2019 → 7 Aug 2025

Decision date (initial)

2024-04-19

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

2023-507498-16-00

EudraCT number

2018-001127-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Others, Safety

Cohort A
To evaluate:
● A preliminary assessment of anti-tumor activity of mosunetuzumab (IV) in patients with best response of stable disease (SD) or partial response (PR) following first-line therapy for DLBCL
● Safety, tolerability, pharmacokinetics (PK) of mosunetuzumab intravenous (IV) in patients previously treated with first-line immunochemotherapy for DLBCL, including determination of the recommended dose for consolidation therapy
Cohort B
To evaluate:
● A preliminary assessment of anti-tumor activity of mosunetuzumab IV in elderly/unfit patients with previously untreated DLBCL
● Safety, tolerability, PK of mosunetuzumab IV in elderly/unfit patients with previously untreated DLBCL
Cohort C:
To evaluate:
● An assessment of overall anti-tumor activity of mosunetuzumab subcutaneous (SC) in combination with polatuzumab vedotin IV in elderly/unfit patients with previously untreated DLBCL
● Safety, tolerability, PK of mosunetuzumab SC in combination with polatuzumab vedotin IV in elderly/unfit patients with previously untreated DLBCL

● PK of polatuzumab vedotin IV when administered in combination with mosunetuzumab SC in elderly/unfit patients with previously untreated DLBCL

Secondary objectives 2

1. To make a preliminary assessment of efficacy of mosunetuzumab IV as a single agent or as SC in combination with polatuzumab vedotin IV
2. To assess the immune response to mosunetuzumab, and polatuzumab vedotin (Cohort C only) and the potential effect of mosunetuzumab anti-drug antibody incidence on relevant clinical outcomes

Conditions and MedDRA coding

Diffuse Large B-Cell Lymphoma (DLBCL)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. For All Cohorts At least one bi-dimensionally measurable nodal (>1.5cm) lesion or extranodal (>1.0 Cm) lesion
2. For All Cohorts Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2. Exception (Cohort C only): in South Korea, patients 80 years or older with ECOG >=2, will not be eligible
3. Cohort A One prior therapy with any systemic anthracycline based chemoimmunotherapy containing regimen for previously untreated DLBCL and Best response of SD or PR to prior systemic chemoimmunotherapy at the end of the induction treatment in accordance with the Lugano 2014 criteria
4. Cohort C Age >= 80 years or Patients who are 65−79 years of age, and considered ineligible for chemoimmunotherapy (R CHOP) at least one of the following: Impairment in >= 2 ADL component and/or Impairment in >= 2 instrumental ADL (IADL) component and/or CIRS-G score of at least 1 comorbidity with a severity score of 3-4 (not including lymphoma and hematologic deficiencies due to lymphoma) or a score of 2 in >=8 comorbidities
5. Cohorts B and C Patients with an initial ECOG performance status of 3 may be considered during screening if the performance status is DLBCL-related and if pre-phase treatment during the screening phase results in an improvement of ECOG performance status to <=2 prior to enrollment
6. Cohort B ≥ 80 years of age, or 60-79 years of age and unfit for full-dose chemotherapy because of poor performance status, impairments in ADL or instrumental activities of daily living (IADL), or other comorbidities

Exclusion criteria 6

1. For All Cohorts Transformed lymphoma, CNS lymphoma
2. For All Cohorts Prior treatment with mosunetuzumab
3. For All Cohorts History of confirmed progressive multifocal leukoencephalopathy (PML)
4. Cohort A Prior anti-lymphoma treatment with chemotherapy, immunotherapy, or biologic therapy within 4 weeks prior to C1D1
5. Cohorts B and C Prior treatment for DLBCL with chemotherapy, immunotherapy, and biologic therapy Exception: patients in Cohort B who are treated with vincristine and prednisone as part of pre-phase treatment or patients in Cohort C who are treated with prednisone as part of pre-phase treatment
6. Cohort C Current Grade >1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Positron emission tomography–computed tomography (PET-CT) complete response (CR) rate or overall response rate (ORR) according to the Lugano 2014 criteria at primary response assessment (PRA) per investigator (INV) for Cohort A and B respectively, and PET-CT ORR at PRA by the IRC for Cohort C
2. 2. Incidence and severity of adverse events

Secondary endpoints 14

1. 1. PET-CT CR per INV for Cohort B and C and per IRC (Cohort C only)
2. 2. Objective response rate (ORR) at PRA per INV Cohort A and C
3. 3. Best ORR per INV in all Cohorts and by IRC in Cohort C
4. 4. Duration of response per INV in all Cohorts and by IRC in Cohort C
5. 5. DOCR, as determined by the investigator in all Cohorts and by the IRC (Cohort C only)
6. 6. Progression-free survival per INV in all Cohorts and by IRC in Cohort C
7. 7. Overall survival
8. 8. Time to deterioration in EORTC QLQ-C30 physical functioning and fatigue, in EORTC IL17 physical functioning, and in the FACT-Lym subscale in Cohorts B and C
9. 9. Proportion of patients achieving a clinically meaningful improvement in physical functioning as measured by EORTC QLQ-C30 and EORTC IL17 (in Cohorts B and C)
10. 10. Incidence of Antidrug antibody (ADA) to mosunetuzumab, and polatuzumab vedotin
11. 11. Relationship between ADAs and PK, safety, efficacy, and biomarkers may be explored as appropriate
12. 12. Maximum serum concentration (Cmax) and minimum serum concentration (Cmin) of mosunetuzumab (IV/SC) and polatuzumab vedotin
13. 13. Total exposure (area under the concentration-time curve [AUC]) of mosunetuzumab (IV/SC) and polatuzumab vedotin
14. 14. Time to maximum concentration (Tmax) of mosunetuzumab SC

Investigational products

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

Test 9

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 7

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

Layperson summary Annex V

Documents 23 files

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

Application history

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