Study of BGB-11417 in Patients With Relapsed or Refractory Mantle Cell Lymphoma

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] - Neoplasms [C04]

Trial duration

4 Apr 2023 → ongoing

Decision date (initial)

2023-07-07

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

BeiGene, Ltd

External identifiers

EU CT number

2022-500687-35-00

WHO UTN

U1111-1279-0851

ClinicalTrials.gov

NCT05471843

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Dose response, Therapy

Part 1 Primary:

To determine the safety and tolerability of BGB-11417 monotherapy

To define the maximum tolerated dose (or maximum administered dose) and the recommended Phase 2 dose of BGB-11417 monotherapy for relapsed or refractory mantle cell lymphoma

To evaluate the safety and tolerability of the ramp-up dosing schedule of BGB 11417 monotherapy in patients with relapsed or refractory mantle cell lymphoma


Part 2 Primary:
To evaluate the efficacy of BGB-11417 monotherapy at the recommended Phase 2 dose with recommended ramp-up schedule from Part 1 in patients with relapsed or refractory MCL.

Secondary objectives 5

1. Part 1 Secondary: To assess the pharmacokinetics of BGB-11417 monotherapy
2. Part 1 Secondary: To assess the preliminary antitumor activity of BGB-11417 monotherapy in patients with relapsed or refractory mantle cell lymphoma.
3. Part 2 Secondary: To evaluate the efficacy of BGB-11417 monotherapy in patients with relapsed or refractory mantle cell lymphoma.
4. Part 2 Secondary: To evaluate the safety and tolerability of BGB-11417 monotherapy in patients with relapsed or refractory mantle cell lymphoma
5. Part 1: To assess the preliminary antitumor activity of BGB-11417 monotherapy in patients with R/R MCL as measured by the ORR, DOR, PFS, and TTR determined by the Independent Review Committee in accordance with the Lugano classification.

Conditions and MedDRA coding

Refractory Mantle Cell Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Histologically confirmed diagnosis of MCL
2. Prior systemic treatments for MCL (at least one line of anti-cluster of differentiate 20 (CD20) based immune or chemoimmunotherapy and at least one line of treatment with covalent or non-covalent Bruton Tyrosine Kinase Inhibitor (BTKi) as mono- or combination therapy)
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 to 2
7. Adequate organ function

Exclusion criteria 7

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 chimeric 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1: Dose limiting toxicity (DLT)
2. Part 1 : The incidence and severity according to the NCI-CTCAE v5.0 of TEAEs, SAEs, and AEs leading to discontinuation of BGB-11417
3. Part 1: Incidence and severity of TLS-relevant events
4. Part 2: Overall response rate as determined by the Independent Review Committee (IRC) in accordance with the Lugano classification

Secondary endpoints 17

1. Part 1:Area Under the Plasma Concentration Time Curve (AUC)
2. Part 1:Maximum Observed Plasma Concentration (Cmax)
3. Part 1: Time to reach Cmax (Tmax)
4. Part 1: Steady State Area Under the Plasma Concentration Time Curve (AUC)
5. Part 1: Steady State Maximum Observed Plasma Concentration (Cmax)
6. Part 1: Steady State Trough Plasma Concentration (CTrough)
7. Part 1: Steady State Time to reach Cmax (Tmax)
8. Overall Response Rate (ORR) as assessed by investigator and IRC. Defined as the proportion of participants who achieved a complete response (CR), or partial response (PR) per Lugano classification
9. Duration of Response (DOR) as assessed by investigator and IRC. DOR is defined as the time from the date of the first documented response (PR or better) after treatment initiation until the date of first documented disease progression or death due to any cause; whichever occurs first
10. Progression Free Survival (PFS) as assessed by investigator and IRC. PFS is defined as the time from the date of the first study dose until the date of first documented disease progression or death due to any cause, whichever occurs first.
11. Time to Response (TTR) as assessed by investigator and IRC. TTR is defined as the time from start of treatment to first documentation of response of Partial Response (PR) or better
12. Overall Survival (OS), defined as time from the start of treatment to the date of death due to any cause.
13. Part 2: Number of Participants Experiencing Adverse Events (AEs)
14. Part 2: Number of participants with clinically significant changes from baseline in vital signs. Vital signs include blood pressure and pulse rate
15. Part 2: Number of participants with clinically significant changes from baseline in clinical laboratory values. Laboratory values include hematology, clinical chemistry, coagulation, and urinalysis
16. Number of Participants With Clinically Significant Physical Examination Findings. A full physical examination includes head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal and musculoskeletal systems
17. Participant Reported Outcomes as measured by NFLymSI-18 and EQ-5D-5L questionnaires

Investigational products

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

Test 4

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

Beigene Ltd.

Contact name

BeOne Medical Officer

Public contact point

Organisation

Beigene Ltd.

Contact name

BeOne Medical Officer

Third parties 13

Locations

6 EU/EEA countries · 17 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 209 files

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

Application history

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