Study to evaluate the efficacy and safety of BGB-11417 in participants with Waldenström’s Macroglobulinemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BeOne Medicines AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

31 Jan 2024 → ongoing

Decision date (initial)

2023-12-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2023-503235-18-00

WHO UTN

U1111-1291-4524

ClinicalTrials.gov

NCT05952037

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of sonrotoclax in patients with WM who have R/R disease to both Bruton tyrosine kinase (BTK) inhibitor and anti CD20 antibody-based systemic therapy containing chemotherapy or proteasome inhibitor (Cohort 1)

Secondary objectives 5

1. To evaluate the efficacy of sonrotoclax monotherapy in Cohorts 1 to 3
2. To evaluate the safety and tolerability of sonrotoclax as monotherapy and in combination with zanubrutinib in patients with WM
3. To measure patient-reported disease- and treatment-specific symptoms and function in Cohorts 1 to 4
4. To evaluate the efficacy of sonrotoclax plus zanubrutinib combination therapy in Cohort 4
5. To determine the recommended dose of sonrotoclax in combination with zanubrutinib in patients with WM

Conditions and MedDRA coding

previously untreated WM

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Age ≥ 18 years.
2. Clinical and definitive histologic diagnosis of WM.
3. Meeting ≥ 1 criterion for treatment according to consensus panel criteria from the 2nd International Workshop on Waldenström’s Macroglobulinemia (IWWM) at study entry.
4. For Cohorts 1 to 3, patients must have R/R disease at study entry unless patients had intolerance to the most recent therapy: • Refractory disease is defined as not attaining at least a MR or progressing while on or within 6 months of completing therapy. • Relapsed disease is defined as attaining at least a MR and meeting the criteria for disease progression beyond 6 months after completing therapy.
5. Adequate organ function.
6. For cohort 1 only, patients must meet the following: - Experienced disease progression on or after BTK inhibitor treatment before next treatment, or treated with BTK inhibitor (continuous treatment for ≥ 12 weeks) without attaining at least a MR. - Experienced disease progression on or after anti CD20 monoclonal antibody based systemic therapy (containing chemotherapy or proteasome inhibitor) before the next treatment, or completed ≥ 2 continuous treatment cycles of therapy without attaining at least a MR.
7. For cohort 2 only, patients must meet the following: - Inability to tolerate a BTK inhibitor despite optimal supportive care measures during BTK inhibitor treatment at the discretion of the investigator. - Experienced disease progression on or after anti-CD20 monoclonal antibody-based systemic therapy (containing chemotherapy or proteasome inhibitor) before the next treatment, or completed ≥ 2 continuous treatment cycles of therapy without attaining at least a MR.
8. For cohort 3 only, patients must meet the following: – Experienced disease progression on or after BTK inhibitor treatment before next treatment, or treated with BTK inhibitor (continuous treatment for ≥ 12 weeks) without attaining at least a MR. – Patients considered by their treating physician to be unsuitable for chemoimmunotherapy regimens.
9. For Cohort 4 only, patients must not have received prior therapy for WM (except for plasmapheresis).

Exclusion criteria 5

1. Central nervous system (CNS) involvement by WM.
2. Transformation to aggressive lymphoma, such as diffuse large B cell lymphoma.
3. History of other malignancies ≤ 2 years before study entry.
4. Having uncontrolled active systemic infection or recent infection requiring parenteral antimicrobial therapy that was completed ≤ 14 days before the first dose of the study drug.
5. Received BCL2 inhibitor previously

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Major response rate (MRR, defined as the proportion of patients achieving partial response [PR] or better per the 11th International Workshop on Waldenström Macroglobulinemia (IWWM) (hereafter as IWWM-11 WM response criteria) as assessed by the Independent Review Committee (Cohort 1)

Secondary endpoints 11

1. MRR as assessed by the IRC in Cohorts 2 and 3 and by the investigator in Cohorts 1 to 4
2. Duration of major response (DoMR) as assessed by the IRC in Cohort 1 to 3 and by the investigator in Cohorts 1 to 4
3. Complete response (CR) + very good partial response (VGPR) rate as assessed by the IRC in Cohorts 1 to 3 and by the investigator in Cohorts 1 to 4
4. Overall response rate (ORR, defined as the proportion of patients achieving minor response [MR] or better) as assessed by the IRC in Cohorts 1 to 3 and by the investigator in Cohorts 1 to 4
5. Progression free survival (PFS) as assessed by the IRC and investigator in Cohorts 1 to 3
6. Time to major response as assessed by the IRC in Cohorts 1 to 3 and by the investigator in Cohorts 1 to 4
7. Overall survival (OS) in Cohorts 1 to 3
8. The frequency and severity of adverse events, serious adverse events, and laboratory abnormalities according to National Cancer Institute Common Terminology for Adverse Event (NCI CTCAE v5.0)
9. Health-related quality of life (HRQoL) based on patient reported outcomes (PRO) using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index 18 Item (NFLymSI-18) Version 4
10. Duration of response (DOR) as assessed by the IRC in Cohorts 1 to 3 and by the investigator in Cohorts 1 to 4
11. Time to next treatment in Cohort 4

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BeOne Medicines AG

Sponsor organisation

BeOne Medicines AG

Address

Aeschengraben 27

City

Basel

Postcode

4051

Country

Switzerland

Scientific contact point

Organisation

BeOne Medicines AG

Contact name

BeOne Medical Officer

Public contact point

Organisation

BeOne Medicines AG

Contact name

BeOne Medical Officer

Third parties 19

Locations

4 EU/EEA countries · 21 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 93 files

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

Application history

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