Clinical trial NCT04973605: 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
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, Dexamethasone/Carfilzomib, Dexamethasone/Daratumumab, and Dexamethasone/Pomalidomide in Patients With Relapsed/Refractory Multiple Myeloma and t(11;14)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory Multiple Myeloma
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2021-07-22
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be assigned sequentially in Part 1. In Part 2 participants will be assigned in parallel
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety, tolerability, and efficacy of sonrotoclax as monotherapy and in various combinations in patients with relapsed/refractory (R/R) multiple myeloma (MM) and chromosomal translocation t(11;14).

The study investigates sonrotoclax alone and in combination with dexamethasone and other agents, including carfilzomib, daratumumab, and pomalidomide.


Eligibility criteria: 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 κ:λ 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. 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.
   2. Participants in Part 2 should have relapsed or progressive disease and have had ≥ 1 prior line of therapy
   3. Prior treatment with carfilzomib is allowed but the patient must not be considered carfilzomib refractory by the investigator.
5. 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.
6. Adequate organ function defined as:

   1. Hemoglobin ≥ 8.0 g/dL within 7 days before first dose of study treatment, (transfusions, in accordance with institutional guidelines, are permitted)
   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/mm\^3 within 7 days before first dose of study treatment
   4. 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)

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. 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. Prior therapy with sonrotoclax or other agents inhibiting BCL2 activity (eg, venetoclax)
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.

Primary outcomes:
measure: Part 1: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs)
timeFrame: Up to 28 days
measure: 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).
timeFrame: Up to 30 days after last dose of study drug
measure: Part 2: Overall response rate (ORR)
timeFrame: Approximately 4 years
measure: Part 2: Very good partial response (VGPR) or better response rate
timeFrame: Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years]
measure: Part 2: Complete Response (CR) or better
timeFrame: Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years])
Secondary outcomes:
measure: Part 1: Area under the plasma concentration-time curve time 0 to the last measurable concentration (AUClast) After a Single Dose of Sonrotoclax
timeFrame: Cycle 1 (each cycle is up to 28 days)
measure: Part 1: Maximum observed plasma concentration (Cmax) After a Single Dose of Sonrotoclax
timeFrame: Cycle 1 (each cycle is up to 28 days)
measure: Part 1: Time to reach Cmax (tmax) After a Single Dose of Sonrotoclax
timeFrame: Cycle 1 (each cycle is up to 28 days)
measure: Part 1: At Steady-state: AUC last, ss
timeFrame: Cycle 2 (each cycle is up to 28 days)
measure: Part 1: At Steady-state: Cmax, ss
timeFrame: Cycle 2 (each cycle is up to 28 days)
measure: Part 1: At Steady-state: trough plasma concentration (Ctrough) ss
timeFrame: Cycle 2 (each cycle is up to 28 days)
measure: Part 1: At Steady-state: time to reach Cmax (tmax,ss)
timeFrame: Cycle 2 (each cycle is up to 28 days)
measure: Part 2: Time to response (TTR) as assessed by investigator
timeFrame: Approximately 4 years
measure: Part 2: Duration of response (DOR) as assessed by investigator
timeFrame: Approximately 4 years
measure: Part 2: Progression-free survival (PFS) as assessed by investigator
timeFrame: Approximately 4 years
measure: Part 2: Overall survival (OS) as assessed by investigator
timeFrame: Approximately 4 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama At Birmingham Hospital
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Irvine
country: United States
facility: City of Hope At Irvine Lennar
state: California
city: San Francisco
country: United States
facility: University of California At San Francisco
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University Winship Cancer Center
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical College Newyork Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Mskcc
state: New York
city: Columbus
country: United States
facility: The James Cancer Hospital and Solove Research Institute At Ohio State University
state: Ohio
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Brasilia
country: Brazil
facility: Hospital Sirio Libanes Brasilia
city: Brasilia
country: Brazil
facility: Instituto Dor de Pesquisa E Ensino Distrito Federal
city: Porto Alegre
country: Brazil
facility: Centro Gaucho Integrado de Oncologia Hospital Mae de Deus
city: Salvador
country: Brazil
facility: Hospital Sao Rafael (Rede Dor)
city: Sao Paulo
country: Brazil
facility: Hospital Sirio Libanes
city: Sao Paulo
country: Brazil
facility: Hospital Nove de Julho Dasa
city: Sao Paulo
country: Brazil
facility: Accamargo Cancer Center
city: Sao Paulo
country: Brazil
facility: Instituto Dor de Pesquisa E Ensino Sao Paulo
city: Sao Paulo
country: Brazil
facility: Clinica Sao Germano
city: Sao Paulo
country: Brazil
facility: Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency the Vancouver Centre
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Beijing
country: China
facility: Beijing Chao Yang Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Peoples Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
state: Guangdong
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Xianghu
state: Jiangxi
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Qingdao
country: China
facility: Qingdao Municipal Hospital
state: Shandong
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Fourth Peoples Hospital Affiliated to Tongji University
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Lille
country: France
facility: Hopital Claude Huriez Chu Lille
city: Nantes
country: France
facility: Centre Hospitalier Universitaire Nantes Hotel Dieu
city: Poitiers
country: France
facility: Chu de Poitiers Site de La Mileterie
city: Aachen
country: Germany
facility: Universitaetsklinikum Aachen
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg Eppendorf
city: Wurzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Alexandroupolis
country: Greece
facility: University Hospital of Alexandroupolis
city: Athens
country: Greece
facility: General Hospital of Athens Alexandra
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv Jaffa
country: Israel
facility: Sourasky Medical Center
city: Bari
country: Italy
facility: Azienda Ospedaliera Policlinico Di Bari
city: Bologna
country: Italy
facility: Policlinico Sorsola Malpighi, Aou Di Bologna
city: Meldola
country: Italy
facility: Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Torino
country: Italy
facility: Istituto Di Candiolo Irccs
city: Torrette
country: Italy
facility: Azienda Ospedaliera Universitaria Delle Marche
city: GangnamGu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: SeochoGu
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St Marys Hospital
state: Seoul Teugbyeolsi
city: SeodaemunGu
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: SongpaGu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Auckland
country: New Zealand
facility: Aotearoa Clinical Trials
city: Singaporeq
country: Singapore
facility: National University Hospital Singapore
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de La Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Headington
country: United Kingdom
facility: Churchill Hospital Oxford University Hospital Nhs Trust
city: London
country: United Kingdom
facility: University College Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Nhs Foundation Royal Marsden Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospitalsnhs Trust
Study officials:
References: