Study of Sonrotoclax (BGB-11417) Monotherapy in Participants With Relapsed or Refractory Mantle Cell Lymphoma

BeOne Medicines

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Mantle Cell Lymphoma; Relapsed Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma (MCL)

Treatments: Drug: Sonrotoclax

Study type: Interventional

Funder types: Industry

Identifiers

NCT05471843

CTR20221815 (Other Identifier)

BGB-11417-201

2022-500687-35-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

The study consists of two parts. Part 1 determines the safety and tolerability of sonrotoclax monotherapy, the maximum tolerated dose, and the recommended Phase 2 dose of sonrotoclax monotherapy for relapsed or refractory mantle cell lymphoma. Part 2 evaluates efficacy of sonrotoclax monotherapy at the recommended Phase 2 dose with recommended ramp-up schedule from Part 1.

Enrollment: 125 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Histologically confirmed diagnosis of MCL
2. Prior systemic treatments for MCL (at least one line of anti-cluster of differentiation 20 (anti-CD20) based immune or chemoimmunotherapy and at least one kind of covalent or non-covalent adequate Bruton Tyrosine Kinase (BTK) inhibitor).
3. Relapsed/refractory disease
4. Presence of measurable disease
5. Availability of archival tissue confirming diagnosis of MCL, or willing to undergo fresh tumor biopsy
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.
7. Adequate organ function

Key Exclusion Criteria:

1. Known central nervous system involvement by lymphoma
2. Prior malignancy other than MCL within the past 3 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer.
3. Prior exposure to a BCL-2 inhibitor (eg, venetoclax/ABT-199).
4. Prior autologous stem cell transplant within the last 3 months; or prior autologous chimeric antigen receptor T-cell therapy within the last 3 months; or prior allogeneic stem cell transplant within the last 6 months or currently has an active graft-vs-host disease requiring the use of immunosuppressants.
5. Clinically significant cardiovascular disease.
6. Major surgery or significant injury ≤ 4 weeks prior to start of study treatment.
7. Active fungal, bacterial or viral infection requiring systemic treatment.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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125 participants in 4 patient groups

Part 1: Sonrotoclax 160 mg (Daily Ramp-up)

Experimental group

Description:

Participants received sonrotoclax at the target dose of 160 mg orally once a day (QD) after an approximately 4-week ramp-up schedule starting at 1 mg with daily dose increases until the target dose was reached. Participants received sonrotoclax until disease progression, unacceptable toxicity, or consent withdrawal.

Treatment:

Drug: Sonrotoclax

Part 1: Sonrotoclax 320 mg (Daily Ramp-up)

Experimental group

Description:

Participants received sonrotoclax at the target dose of 320 mg orally once a day after an approximately 4-week ramp-up schedule starting at 1 mg with daily dose increases until the target dose was reached. Participants received sonrotoclax until disease progression, unacceptable toxicity, or consent withdrawal.

Treatment:

Drug: Sonrotoclax

Part 2: Sonrotoclax 320 mg (Daily Ramp-up)

Experimental group

Description:

Participants received sonrotoclax at the target dose of 320 mg orally once a day after an approximately 4-week ramp-up schedule starting at 1 mg with daily dose increases until the target dose was reached. Participants received sonrotoclax until disease progression, unacceptable toxicity, or consent withdrawal.

Treatment:

Drug: Sonrotoclax

Part 2: Sonrotoclax 320 mg (Twice-weekly Ramp-up)

Experimental group

Description:

Participants received sonrotoclax at the target dose of 320 mg orally once a day after an approximately 4-week ramp-up schedule starting at 1 mg with twice-weekly dose increases until the target dose was reached. Participants received sonrotoclax until disease progression, unacceptable toxicity, or consent withdrawal.

Treatment:

Drug: Sonrotoclax