A Phase 1b/2 Study of Sonrotoclax (BGB-11417) as Monotherapy and in Various Combinations With Dexamethasone Plus Carfilzomib, Dexamethasone Plus Daratumumab, and Dexamethasone Plus Pomalidomide in Multiple Myeloma
- Conditions
- Relapsed/Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT04973605
- Lead Sponsor
- BeiGene
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 167
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
-
A confirmed diagnosis of multiple myeloma (must have an M-component in serum and/or urine)
-
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 κ:λ ratio
-
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.
- In Part 1 should have relapsed or progressive disease and have had ≥ 3 prior lines of therapy including a proteasome inhibitor, an IMiD, and an anti-CD38 monoclonal antibody, and no more available approved therapies.
- Participants in Part 2 should have relapsed or progressive disease and have had ≥ 1 prior line of therapy
- Prior treatment with carfilzomib is allowed but the patient must not be considered carfilzomib refractory by the investigator.
-
Positivity for t(11;14) translocation must be confirmed 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.
-
Adequate organ function defined as:
- Hemoglobin ≥ 8.0 g/dL within 7 days before first dose of study treatment, (transfusions, in accordance with institutional guidelines, are permitted)
- Platelet count ≥ 75,000/μL, within 7 days before first dose of study treatment, independent of growth factor support and transfusions
- Absolute neutrophil count (ANC) ≥ 1000/mm^3 within 7 days before first dose of study treatment
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) and total bilirubin ≤ 2.0 x ULN N (total bilirubin must be < 3 x ULN for patients with Gilbert's syndrome)
-
Participant has any of the following conditions:
- Non secretory MM (Serum free light chains < 10 mg/dL)
- Solitary plasmacytoma
- Active plasma cell leukemia (ie, either 20% of peripheral white blood cells or > 2.0 x 109/L circulating plasma cells by standard differential)
- Waldenström macroglobulinemia
- Amyloidosis.
- Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome
- Chronic respiratory disease that requires continuous oxygen
-
Significant cardiovascular disease, including but not limited to:
- Myocardial infarction ≤ 6 months before screening
- Ejection fraction ≤ 50%
- Unstable angina≤ 3 months before screening
- New York Heart Association Class III or IV congestive heart failure
- History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
- Heart rate-corrected QT interval > 480 milliseconds based on Fridericia's formula
- History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
- Uncontrolled hypertension at screening, defined as systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mmHg by ≥ 2 consecutive measurements. Prior therapy with sonrotoclax or other agents inhibiting BCL2 activity (eg, venetoclax)
-
Known infection with human immunodeficiency virus (HIV)
-
Serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection as follows:
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 Dose Escalation Pomalidomide Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) Part 1 Dose Escalation Dexamethasone Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) Part 1 Dose Escalation Carfilzomib Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) Part 1 Dose Escalation Daratumumab Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) Part 2 Cohort Expansion Dexamethasone There will be 5 expansion cohorts to further evaluate the safety and efficacy of BGB-11417 Part 2 Cohort Expansion Carfilzomib There will be 5 expansion cohorts to further evaluate the safety and efficacy of BGB-11417 Part 1 Dose Escalation Sonrotoclax Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) Part 2 Cohort Expansion Sonrotoclax There will be 5 expansion cohorts to further evaluate the safety and efficacy of BGB-11417
- Primary Outcome Measures
Name Time Method Part 1 And 2: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation and Adverse Events of Special Interest (AESIs). Up to 30 days after last dose of study drug Part 2: Very good partial response (VGPR) or better response rate Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years] Defined as the percentage of participants with a documented VGPR or better (including sCR, CR, and VGPR)
Part 1: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs) Up to 28 days DLTs will be based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and will include most grade 3 or higher events, as defined in the protocol.
Part 2: Overall response rate (ORR) Approximately 4 years Defined as the percentage of participants 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
Part 2: Complete Response (CR) or better Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years]) defined as the percentage of participants with a documented CR or sCR
- Secondary Outcome Measures
Name Time Method Part 1: Area under the plasma concentration-time curve time 0 to the last measurable concentration (AUClast) After a Single Dose of Sonrotoclax Cycle 1 (each cycle is up to 28 days) Part 1: Time to reach Cmax (tmax) After a Single Dose of Sonrotoclax Cycle 1 (each cycle is up to 28 days) Part 1: Maximum observed plasma concentration (Cmax) After a Single Dose of Sonrotoclax Cycle 1 (each cycle is up to 28 days) Part 1: At Steady-state: trough plasma concentration (Ctrough) ss Cycle 2 (each cycle is up to 28 days) Part 1: At Steady-state: AUC last, ss Cycle 2 (each cycle is up to 28 days) Part 1: At Steady-state: time to reach Cmax (tmax,ss) Cycle 2 (each cycle is up to 28 days) Part 2: Time to response (TTR) as assessed by investigator Approximately 4 years TTR is defined as the time from start of treatment (for nonrandomized cohorts) or date of randomization (for randomized cohorts to first documentation of response of Partial Response (PR) or better
Part 1: At Steady-state: Cmax, ss Cycle 2 (each cycle is up to 28 days) Part 2: Progression-free survival (PFS) as assessed by investigator Approximately 4 years PFS is defined as time from start of treatment to the first documentation of disease progression or death, whichever occurs first
Part 2: Duration of response (DOR) as assessed by investigator Approximately 4 years 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. DOR will be analyzed 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.
Part 2: Overall survival (OS) as assessed by investigator Approximately 4 years OS defined as the time from start of treatment (for nonrandomized cohorts) or date of randomization (for randomized cohorts to the date of death due to any cause
Trial Locations
- Locations (89)
University of Alabama At Birmingham Hospital
🇺🇸Birmingham, Alabama, United States
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
Hospital Sao Rafael (Rede Dor)
🇧🇷Salvador, Brazil
Hospital Sirio Libanes
🇧🇷Sao Paulo, Brazil
Instituto Dor de Pesquisa E Ensino Sao Paulo
🇧🇷Sao Paulo, Brazil
Hospital Nove de Julho Dasa
🇧🇷Sao Paulo, Brazil
Accamargo Cancer Center
🇧🇷Sao Paulo, Brazil
Clinica Sao Germano
🇧🇷Sao Paulo, Brazil
Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
🇧🇷Sao Paulo, Brazil
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
British Columbia Cancer Agency the Vancouver Centre
🇨🇦Vancouver, British Columbia, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Beijing Chao Yang Hospital
🇨🇳Beijing, Beijing, China
Sun Yat Sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
The Second Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
Fondazione Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
Istituto Di Candiolo Irccs
🇮🇹Torino, Italy
Azienda Ospedaliera Universitaria Delle Marche
🇮🇹Torrette, Italy
Seoul National University Hospital
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
City of Hope National Medical Center
🇺🇸Duarte, California, United States
City of Hope At Irvine Lennar
🇺🇸Irvine, California, United States
University of California At San Francisco
🇺🇸San Francisco, California, United States
University of Miami
🇺🇸Miami, Florida, United States
Emory University Winship Cancer Center
🇺🇸Atlanta, Georgia, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Weill Cornell Medical College Newyork Presbyterian Hospital
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center Mskcc
🇺🇸New York, New York, United States
The James Cancer Hospital and Solove Research Institute At Ohio State University
🇺🇸Columbus, Ohio, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
University of Washington
🇺🇸Seattle, Washington, United States
University of Wisconsin Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Canberra Hospital
🇦🇺Garran, Australian Capital Territory, Australia
Nepean Hospital
🇦🇺Kingswood, New South Wales, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
St Vincents Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Peking University Peoples Hospital
🇨🇳Beijing, Beijing, China
Chongqing Cancer Hospital
🇨🇳Chongqing, Chongqing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, 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, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Nanchang University Branch Xianghu
🇨🇳Nanchang, Jiangxi, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, 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
Tianjin Medical University General Hospital
🇨🇳Tianjin, Tianjin, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Hopital Claude Huriez Chu Lille
🇫🇷Lille, France
Centre Hospitalier Universitaire Nantes Hotel Dieu
🇫🇷Nantes Cedex, France
Chu de Poitiers Site de La Mileterie
🇫🇷Poitiers, France
Universitaetsklinikum Aachen
🇩🇪Aachen, Germany
Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
🇩🇪Dresden, Germany
Universitatsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
Universitatsklinikum Wurzburg
🇩🇪Wurzburg, Germany
University Hospital of Alexandroupolis
🇬🇷Alexandroupolis, Greece
General Hospital of Athens Alexandra
🇬🇷Athens, Greece
Rabin Medical Center
🇮🇱Petach Tikva, Israel
Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Azienda Ospedaliera Policlinico Di Bari
🇮🇹Bari, Italy
Policlinico Sorsola Malpighi, Aou Di Bologna
🇮🇹Bologna, Italy
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst
🇮🇹Meldola, Italy
Istituto Europeo Di Oncologia
🇮🇹Milano, Italy
Samsung Medical Center
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
The Catholic University of Korea, Seoul St Marys Hospital
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Aotearoa Clinical Trials
🇳🇿Auckland, New Zealand
National University Hospital Singapore
🇸🇬Singapore, Singapore
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital San Pedro de Alcantara
🇪🇸Caceres, Spain
Hospital Universitario Virgen de La Victoria
🇪🇸Malaga, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Churchill Hospital Oxford University Hospital Nhs Trust
🇬🇧Headington, United Kingdom
University College Hospital
🇬🇧London, United Kingdom
Royal Marsden Nhs Foundation Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Royal Cornwall Hospitalsnhs Trust
🇬🇧Truro, United Kingdom