A Phase 1b/2 Study of BGB-11417in Monotherapy and in Various Combinations With Dexamethasone and Carfilzomib in Multiple Myeloma

Relapsed/Refractory Multiple Myeloma Clinical Trial

Official title:

A Phase 1b/2 Dose-Escalation and Cohort-Expansion Study to Determine the Safety and Efficacy of BGB-11417as Monotherapy, in Combination With Dexamethasone and Carfilzomib/Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma and t(11;14)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04973605
• Other study ID #: BGB-11417-105
• Secondary ID: 2021-003614-39U1
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 16, 2021
• Est. completion date: November 2026

Study information

• Verified date: June 2024
• Source: BeiGene
• Contact: BeiGene
• Phone: 1.877.828.5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study consists of two parts, a part 1 dose escalation and a part 2 cohort expansion in combination with dexamethasone and carfilzomib intravenously across two cohorts with a monotherapy component as well.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 167
• Est. completion date: November 2026
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

2. A confirmed diagnosis of multiple myeloma (must have an M-component in serum and/or urine)

3. Measurable disease defined as:

i. M-spike = 500mg/dL, or ii. Urine protein M-spike of = 200 mg/day, or iii. Serum free light chains = 10 mg/dL, and an abnormal ?:? ratio

4. Participant has documented relapsed or progressive MM on or after any regimen or who are refractory to the most recent line of therapy.

i. Relapsed MM is defined as previously treated MM that progresses and requires initiation of salvage therapy but does not meet the criteria for refractory MM.

ii. Refractory MM is defined as disease that is nonresponsive (failure to achieve minimal response or development of progressive disease) while on primary or salvage therapy or progresses within 60 days of last therapy.

1. Participants in Part 1 should have failed all other available options including having had = 3 prior lines of therapy including a proteasome inhibitor, IMiD agent, and an anti-CD38 monoclonal antibody.

2. Participants in Part 2 should have had and failed = 1 but = 7 prior lines of therapy and will have had prior treatment with both a proteasome inhibitor and an IMiD agent.

Note: A line of therapy consists of greater = 1 complete cycle of a single agent, a regimen consisting of combination of several drugs, or a planned sequential therapy of various regimens. Induction therapy with consolidation and maintenance following stem cell transplant is considered a single line of therapy.

3. Prior treatment with carfilzomib is allowed but the patient must not be considered carfilzomib refractory and not have had carfilzomib within the past 6 months

5. Positivity for t(11;14) by validated fluorescence in situ hybridization (FISH) testing assay in a pre-defined laboratory

a. fresh bone marrow aspirate sample must be collected at screening and sent to central laboratory for t(11;14) FISH testing.

6. Adequate organ function defined as:

1. Hemoglobin = 8.0 g/dL, within 7 days before first dose of study treatment, independent of growth factor support and transfusions

2. Platelet count = 75,000/µL, within 7 days before first dose of study treatment, independent of growth factor support and transfusions

3. Absolute neutrophil count (ANC) = 1000/mm3 [ANC = (% of segmented neutrophils + % of segmented bands) x total WBC count within 7 days before first dose of study treatment

4. ALT and AST = 3 x upper limit of normal (ULN) and total bilirubin = 2.0 x ULN Serum creatinine = 1.5 x ULN or creatinine clearance = 45 mL/min/1.73 m2 calculated by the MDRD-6 formula.

Exclusion Criteria:

1. Participant has any of the following conditions:

1. Non secretory MM (Serum free light chains < 10 mg/dL)

2. Solitary plasmacytoma

3. Active plasma cell leukemia (ie, either 20% of peripheral white blood cells or > 2.0 x 109/L circulating plasma cells by standard differential)

4. Waldenström macroglobulinemia

5. Amyloidosis.

6. Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome

7. Uncontrolled diabetes (HbA1c > 7% or 53 mmol/mol or requiring insulin at study entry

8. Chronic respiratory disease that requires continuous oxygen

2. Significant cardiovascular disease, including but not limited to:

1. Myocardial infarction = 6 months before screening

2. Ejection fraction = 50%

3. Unstable angina= 3 months before screening

4. New York Heart Association Class III or IV congestive heart failure

5. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes)

6. Heart rate-corrected QT interval > 480 milliseconds based on Fridericia's formula

7. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place

8. Uncontrolled hypertension at screening, defined as systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mmHg by = 2 consecutive measurements

3. Known infection with human immunodeficiency virus (HIV)

4. Serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection as follows:

1. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Participants with presence of HBcAb, but absence of HBsAg, are eligible if HBV DNA is undetectable (limitation of sensitivity < 20 IU/mL) ,), and if they are willing to undergo monthly monitoring for HBV reactivation.

2. Presence of HCV antibody. Participants with presence of HCV antibody are eligible if HCV RNA is undetectable (limitation of sensitivity < 15 IU/mL).

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/Refractory Multiple Myeloma

Intervention

Drug:
• BGB-11417
Administered orally daily
• Dexamethasone
Once weekly either orally or intravenously
• Carfilzomib
Administered intravenously weekly

Locations

Country	Name	City	State
Australia	Monash Health	Clayton	Victoria
Australia	St Vincents Hospital Melbourne	Fitzroy	Victoria
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Brazil	Hospital Sirio Libanes Brasilia	Brasilia
Brazil	Instituto Dor de Pesquisa E Ensino Distrito Federal	Brasilia
Brazil	Centro Gaucho Integrado de Oncologia Hospital Mae de Deus	Porto Alegre
Brazil	Accamargo Cancer Center	Sao Paulo
Brazil	Clinica Sao Germano	Sao Paulo
Brazil	Hospital Nove de Julho Dasa	Sao Paulo
Brazil	Hospital Sirio Libanes Sao Paulo	Sao Paulo
Brazil	Instituto Dor de Pesquisa E Ensino Sao Paulo	Sao Paulo
Brazil	Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein	Sao Paulo
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	British Columbia Cancer Agency the Vancouver Centre	Vancouver	British Columbia
China	Beijing Chao Yang Hospital	Beijing	Beijing
China	Peking University Peoples Hospital	Beijing	Beijing
China	Hunan Cancer Hospital	Changsha	Hunan
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Sun Yat Sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Nanchang University Branch Xianghu	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Qingdao Municipal Hospital	Qingdao	Shandong
China	Affiliated Zhongshan Hospital of Fudan University	Shanghai	Shanghai
China	Shanghai Fourth Peoples Hospital Affiliated to Tongji University	Shanghai	Shanghai
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
Israel	Rabin Medical Center	Petach Tikva
Israel	Sourasky Medical Center	Tel Aviv
Korea, Republic of	Asan Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Samsung Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul	Seoul Teugbyeolsi
Korea, Republic of	The Catholic University of Korea, Seoul St Marys Hospital	Seoul	Seoul Teugbyeolsi
New Zealand	Aotearoa Clinical Trials	Auckland
Singapore	National University Hospital Singapore	Singapore
United Kingdom	University College Hospital	London
United Kingdom	Royal Marsden Nhs Foundation Royal Marsden Hospital	Sutton
United Kingdom	Royal Cornwall Hospitalsnhs Trust	Truro
United States	Luminis Health Anne Arundel Medical Center	Annapolis	Maryland
United States	Emory University Winship Cancer Center	Atlanta	Georgia
United States	University of Alabama At Birmingham Hospital	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	The James Cancer Hospital and Solove Research Institute At Ohio State University	Columbus	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	City of Hope At Irvine Lennar	Irvine	California
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Memorial Sloan Kettering Cancer Center Mskcc	New York	New York
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	University of Washington	Seattle	Washington
United States	Southern Illinois University School of Medicine	Springfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  China,  Israel,  Korea, Republic of,  New Zealand,  Singapore,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs)	DLTs will be based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and will be defined as any of following events: Grade 3 or higher toxicity assessed by the investigator as related to BGB-11417 treatment; and Grade 4 or higher regimen-related organ toxicities	Cycle 1 (Up to 28 days for non-hematologic DLTs and up to 42 days for hematologic DLTs)
Primary	Part 1 And 2: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) with adverse events leading to discontinuation, and AEs graded according NCI-CTCAE Version 5		Up to 24 months after last dose of study drug
Primary	Part 2: Overall response rate (ORR)	Defined as the proportion of patients who achieved a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per International Myeloma Working Group (IMWG) criteria	Approximately 4 years
Primary	Part 2: Very good partial response (VGPR) or better response rate	Defined as the proportion of patients with a documented VGPR or better (including sCR, CR, and VGPR)	Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years]
Primary	Part 2: Complete Response (CR) or better	defined as the proportion of patients with a documented CR or sCR	Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years])
Secondary	Part 1: Area under the plasma concentration-time curve (AUC)		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Part 1: Maximum observed plasma concentration (Cmax)		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Part 1: Time to reach Cmax (tmax)		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Part 1: After steady-state: AUC last,ss		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Part 1: After steady-state: Cmax, ss		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Part 1: After steady-state: trough plasma concentration (Ctrough) ss		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Part 1: After steady-state: time to reach Cmax (tmax,ss)		At the end of Cycle 1 (each cycle is 28 days)
Secondary	Part 2: Time to response (TTR) as assessed by investigator	TTR is defined as the time from start of treatment to first documentation of response of Partial Response (PR) or better	Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years])
Secondary	Part 2: Duration of response (DOR) as assessed by investigator	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 MM, whichever occurs first. DOR will be analyzed using the same methods as the PFS analysis, but only for patients who have achieved an overall response of at least PR. The distribution of DOR will be summarized by the Kaplan-Meier method.	Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years])
Secondary	Part 2: Progression-free survival (PFS) as assessed by investigator	PFS is defined as time from start of treatment to the first documentation of disease progression or death, whichever occurs first	Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years])
Secondary	Part 2: Overall survival (OS) as assessed by investigator	OS defined as the time from start of treatment to the date of death due to any cause	Upon study termination (Baseline up to approximately 4 years)