A Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination with Polatuzumab Vedotin in Patients with B-Cell Non-Hodgkin 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], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

27 Dec 2021 → ongoing

Decision date (initial)

2023-12-19

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

2023-506986-74-00

EudraCT number

2018-001141-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Others

Phase Ib To evaluate the safety and tolerability of mosunetuzumab (Mosun) + polatuzumab vedotin (Pola) in patients with relapsed or refractory (R/R) DLBCL or follicular lymphoma (FL), including estimation of maximum tolerated dose, determination of recommended Phase II dose (RP2D), characterization of dose-limiting toxicity (DLT) To make a preliminary assessment of the anti-tumor activity of Mosun + Pola Phase II: To evaluate the efficacy of Mosun (IV) plus Pola in patients with R/R FL and R/R DLBCL, based on best objective response rate (ORR) in the study, as determined by the Independent Review Committee (IRC) To evaluate the efficacy of Mosun (SC) plus Pola in patients with R/R DLBCL and R/R MCL based on best ORR in the study, as determined by the Independent Review Committee (IRC)

Secondary objectives 8

1. Phase Ib and II To characterize the pharmacokinetics of Mosun (SC and IV) as a single agent and when administered in combination with Pola
2. Phase Ib and II To assess the incidence of anti-drug antibodies (ADAs) to Mosun and Pola
3. Phase II To evaluate the efficacy of Mosun + Pola in R/R DLBCL (Mosun SC and IV), R/R FL (Mosun IV), and R/R MCL (Mosun SC), based on best ORR as determined by the investigator; best complete response (CR) rate; CR rate by at primary response assessment (PRA); ORR at PRA; duration of response (DOR); progression-free survival (PFS); event-free survival (EFS) and overall survival (OS)
4. Phase II To evaluate the safety of Mosun + Pola in R/R DLBCL (Mosun SC and IV), R/R FL (Mosun IV), and R/R MCL (Mosun SC)
5. Phase Ib and II To characterize the pharmacokinetics of Mosun (SC and IV) as a single agent and when administered in combination with Pola
6. Phase Ib and II To assess the incidence of anti-drug antibodies (ADAs) to Mosun and Pola
7. Phase II To evaluate the efficacy of Mosun + Pola in R/R DLBCL (Mosun SC and IV), R/R FL (Mosun IV), and R/R MCL (Mosun SC), based on best ORR as determined by the investigator; best complete response (CR) rate; CR rate by at primary response assessment (PRA); ORR at PRA; duration of response (DOR); progression-free survival (PFS); event-free survival (EFS) and overall survival (OS)
8. Phase II To evaluate the safety of Mosun + Pola in R/R DLBCL (Mosun SC and IV), R/R FL (Mosun IV), and R/R MCL (Mosun SC)

Conditions and MedDRA coding

B-cell non-Hodgkin lymphoma (NHL)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Age ≥ 18 years at time of signing Informed Consent Form
2. Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
3. Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension.
4. Patients must have histologically confirmed R/R FL, DLBCL, or MCL
5. For DLBCL or FL, must have received at least one prior systemic treatment regimen containing an anti- cluster of differentiation 20 (CD20) - directed therapy
6. For MCL, must have received at least two prior systemic treatment regimens which include agents from all three classes below: anti-CD20-directed therapy, a Bruton’s tyrosine kinase (BTK) inhibitor, and an anthracycline or bendamustine
7. Age ≥ 18 years at time of signing Informed Consent Form
8. Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
9. Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension.
10. Patients must have histologically confirmed R/R FL, DLBCL, or MCL
11. For DLBCL or FL, must have received at least one prior systemic treatment regimen containing an anti- cluster of differentiation 20 (CD20) - directed therapy
12. For MCL, must have received at least two prior systemic treatment regimens which include agents from all three classes below: anti-CD20-directed therapy, a Bruton’s tyrosine kinase (BTK) inhibitor, and an anthracycline or bendamustine

Exclusion criteria 12

1. Current eligibility for autologous SCT in patients with R/R DLBCL, R/R transformed FL, or R/R Grade 3b FL
2. Pregnant or lactating women
3. Prior treatment with Mosun or other CD20-directed bispecific antibodies or with Pola
4. Current > Grade 1 peripheral neuropathy
5. Prior use of any monoclonal antibodies, radioimmunoconjugates or antibody-drug conjugates for anti-lymphoma treatment within 4 weeks before first dose of study treatment
6. Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
7. Current eligibility for autologous SCT in patients with R/R DLBCL, R/R transformed FL, or R/R Grade 3b FL
8. Pregnant or lactating women
9. Prior treatment with Mosun or other CD20-directed bispecific antibodies or with Pola
10. Current > Grade 1 peripheral neuropathy
11. Prior use of any monoclonal antibodies, radioimmunoconjugates or antibody-drug conjugates for anti-lymphoma treatment within 4 weeks before first dose of study treatment
12. Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. 1. Occurrence and severity of adverse events, including DLTs (Phase Ib)
2. 2. Change from baseline in targeted vital signs (Phase Ib)
3. 3. Change from baseline in targeted clinical laboratory test results (Phase Ib)
4. 4. CR rate at the time of PRA as determined by the investigator (Phase Ib)
5. 5. Best ORR as determined by the investigator (Phase Ib)
6. 6. DOR as determined by the investigator (Phase Ib)
7. 7. Best ORR, as determined by the IRC (Phase II)

Secondary endpoints 17

1. 1. Best ORR as determined by the investigator (Phase II)
2. 2. Best CR rate as determined by the investigator and IRC (Phase II)
3. 3. CR rate at the time of PRA as determined by the investigator and IRC (Phase II)
4. 4. ORR at the time of PRA as determined by the investigator and IRC (Phase II)
5. 5. DOR as determined by the investigator and IRC (Phase II)
6. 6. PFS as determined by the investigator and IRC (Phase II)
7. 7. EFS as determined by the investigator and IRC (Phase II)
8. 8. OS (Phase II)
9. 9. Occurrence and severity of adverse events (Phase II)
10. 10. Change from baseline in targeted vital signs (Phase II)
11. 11. Change from baseline in targeted clinical laboratory test results (Phase II)
12. 12. Maximum serum concentration (Cmax) for Mosun (Phase Ib and II)
13. 13. Minimum serum concentration (Cmin) for Mosun (Phase Ib and II)
14. 14. Total exposure area under the concentration-time curve (AUC) for Mosun (Phase Ib and II)
15. 15. Clearance for Mosun (Phase Ib and II)
16. 16. Volume of distribution for Mosun (Phase Ib and II)
17. 17. Relationship between ADA status and efficacy, safety, pharmacokinetics, and biomarkers (Phase Ib and II)

Investigational products

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

Test 7

Auxiliary 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 Support Line - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information Support Line - TISL

Third parties 11

Locations

2 EU/EEA countries · 8 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 36 files

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

Application history

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