Clinical trial • Phase I/II • Oncology

N-[4-({[(1R,4R)-4-HYDROXY-4-METHYLCYCLOHEXYL]METHYL}AMINO)-3-NITROBENZENE-1-SULFONYL]-4-(2-{(2S)-2-[2-(PROPAN-2-YL)PHENYL]PYRROLIDIN1-YL}-7-AZASPIRO[3.5]NONAN-7-YL)-2-[(1H-PYRROLO[2,3-B]PYRIDIN-5-YL)OXY]BENZAMIDE for Multiple myeloma|Relapsed/refractory multiple myeloma

Phase I/II trial of N-[4-({[(1R,4R)-4-HYDROXY-4-METHYLCYCLOHEXYL]METHYL}AMINO)-3-NITROBENZENE-1-SULFONYL]-4-(2-{(2S)-2-[2-(PROPAN-2-YL)PHENYL]PYRROLIDIN1-…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Multiple myeloma|Relapsed/refractory multiple myeloma
Trial Stage
Phase I/II
Drug Modality
Small molecule|Monoclonal antibody
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
30-11-2023
First CTIS Authorization Date
12-04-2024

Trial design

Randomised, open-label, imnovid (pomalidomide, hard capsules) — comparator product listed (imnovid 1 mg hard capsules); dexamethasone (oral and iv) — comparator; kyprolis (carfilzomib, powder for solution for infusion, product name kyprolis 60 mg) — comparator; darzalex (daratumumab 1800 mg solution for injection, subcutaneous) — comparator. (no dosing schedules in-protocol text provided beyond product names and formulations.)-controlled, adaptive Phase I/II trial in Germany, Spain, Greece and others.

Randomised
Yes
Open Label
Yes
Comparator
Imnovid (pomalidomide, hard capsules) — comparator product listed (Imnovid 1 mg hard capsules); Dexamethasone (oral and IV) — comparator; Kyprolis (carfilzomib, powder for solution for infusion, product name Kyprolis 60 mg) — comparator; DARZALEX (daratumumab 1800 mg solution for injection, subcutaneous) — comparator. (No dosing schedules in-protocol text provided beyond product names and formulations.)
Adaptive
True; the study includes a dose-escalation Part 1 to determine MTD/MAD and RP2D with protocol-defined DLT assessment and subsequent cohort-expansion Part 2 (adaptive dose-escalation to determine recommended Phase 2 dose and cohort expansion based on safety/tolerability and efficacy).
Biomarker Stratified
True, biomarker: t(11;14) translocation confirmed by validated central FISH assay (enrolment requires centrally confirmed t(11;14))
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
141

Eligibility

Recruits 141 adults.

Inclusion criteria

  • {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2\n- A confirmed diagnosis of multiple myeloma\n- Measurable disease defined as: (a) M-spike ≥ 500 mg/dL, or (b) Urine protein M-spike of ≥ 200 mg/day, or (c) Serum free light chains ≥ 10 mg/dL, and an abnormal κ:λ ratio\n- Patient has documented relapsed or progressive MM on or after any regimen or who are refractory to the most recent line of therapy. 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. 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.\n- Patients in Part 1 (all cohorts) 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 therapies.\n- Patients in Part 2 (Cohorts 1 and 2) 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 therapies.\n- Patients in Part 2 (Cohorts 3, 4 and 5): (i) Should have relapsed or progressive disease and have had ≥ 1 prior line of therapy. Patients must have been exposed to a combination therapy containing an anti-CD38 monoclonal antibody. Prior treatment with carfilzomib is allowed, but the patient must not be considered carfilzomib refractory by the investigator.\n- Positivity for t(11;14) translocation must be confirmed by a validated FISH assay in a predefined central laboratory: (a) A fresh bone marrow aspirate sample must be collected at screening and sent to central laboratory for t(11;14) FISH testing; (b) Enrollment requires centrally confirmed t(11;14) results.\n- Adequate organ function defined as: (a) Hemoglobin ≥ 8.0 g/dL within 7 days before first dose of study treatment (transfusions, in accordance with institutional guidelines, are permitted); (b) Platelet count ≥ 75,000/μL within 7 days before first dose of study treatment, independent of growth factor support and transfusions; (c) Absolute neutrophil count (ANC) ≥ 1000/mm3 within 7 days before first dose of study treatment; (d) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) and total bilirubin ≤ 2.0 x ULN; (e) Creatinine clearance ≥ 45 mL/min/1.73 m2 as calculated by the MDRD-6 formula."}

Exclusion criteria

  • {"criterion_text":"- Patient has any of the following conditions: (a) Non secretory MM (Serum free light chains < 10 mg/dL); (b) Solitary plasmacytoma; (c) Active plasma cell leukemia (5% of peripheral white blood cells); (d) Waldenström macroglobulinemia; (e) Amyloidosis; (f) Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome.\n- Chronic respiratory disease that requires continuous oxygen and/or respiratory failure requiring assisted ventilation\n- Significant cardiovascular disease, including but not limited to: (a) Myocardial infarction ≤ 6 months before screening; (b) Ejection fraction ≤ 50%; (c) Unstable angina ≤ 3 months before screening; (d) New York Heart Association Class III or IV congestive heart failure; (e) History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes); (f) Heart rate-corrected QT interval > 480 milliseconds based on Fridericia’s formula; (g) History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place; (h) Uncontrolled hypertension at screening, defined as systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg by ≥ 2 consecutive measurements.\n- Positive human immunodeficiency virus serology (HIVAb) status.\n- Serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection as follows: (a) Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients 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. (b) Presence of HCV antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable (limitation of sensitivity < 15 IU/mL)."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Part 1 (Dose Escalation): Safety and tolerability of sonrotoclax in combination with dexamethasone, dexamethasone plus carfilzomib, dexamethasone plus daratumumab, and dexamethasone plus pomalidomide as assessed by (a) Protocol-defined dose limiting toxicities (DLTs), and (b) The incidence, timing, and severity of treatment-emergent adverse events (TEAEs), serious adverse events, adverse events leading to discontinuation, and adverse events of special interest (AESIs) per NCI CTCAE v5.0","definition_or_measurement_approach":"Assessment based on protocol-defined DLTs and incidence/timing/severity of TEAEs, SAEs, AEs leading to discontinuation, and AESIs per NCI CTCAE v5.0"}
  • {"endpoint_text":"- Part 2 (Cohort Expansion): Safety and tolerability of sonrotoclax at the recommended Phase 2 dose (RP2D) as monotherapy, in combination with dexamethasone, and in combination with dexamethasone plus carfilzomib at the recommended dose combination(s), as assessed based on the incidence, timing, and severity of DLTs (for sonrotoclax monotherapy only), TEAEs, serious adverse events, adverse events leading to discontinuation, and AESIs according to NCI-CTCAE v5.0","definition_or_measurement_approach":"Assessment based on incidence/timing/severity of DLTs (monotherapy), TEAEs, SAEs, AEs leading to discontinuation, and AESIs per NCI-CTCAE v5.0"}
  • {"endpoint_text":"- Part 2 (Cohort Expansion): 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) guidelines","definition_or_measurement_approach":"ORR measured as proportion of patients achieving sCR, CR, VGPR, or PR per IMWG guidelines"}
  • {"endpoint_text":"- Part 2 (Cohort Expansion): VGPR or better response rate, defined as the proportion of patients with a documented VGPR or better (including sCR, CR, and VGPR)","definition_or_measurement_approach":"Proportion of patients with documented VGPR or better (includes sCR, CR, VGPR)"}
  • {"endpoint_text":"- Part 2 (Cohort Expansion): CR or sCR rate, defined as the proportion of patients with a documented CR or sCR.","definition_or_measurement_approach":"Proportion of patients with documented CR or sCR"}

Secondary endpoints

  • {"endpoint_text":"- Part 1 (Dose Escalation): Derived PK parameters of sonrotoclax, including: (a) For a single dose: area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUClast), maximum observed plasma concentration (Cmax), and time to reach Cmax (tmax) as appropriate. (b) After steady-state (ss): AUClast,ss, Cmax,ss, trough plasma concentration (Ctrough) ss, and tmax,ss. Other PK parameters may be reported.","definition_or_measurement_approach":"Pharmacokinetic parameters derived from plasma concentration-time data (AUClast, Cmax, tmax for single dose; AUClast,ss, Cmax,ss, Ctrough,ss, tmax,ss at steady-state)"}
  • {"endpoint_text":"- Part 2 (Cohort Expansion): Time to response (TTR) as assessed by investigator, defined as the time from start of treatment (for nonrandomized cohorts) or date of randomization (for randomized cohorts [Part 2 Cohorts 3, 4, and 5]) to first documentation of response of PR or better.","definition_or_measurement_approach":"Time (days) from treatment start or randomization to first documented PR or better as assessed by investigator"}
  • {"endpoint_text":"- Part 2 (Cohort Expansion): Duration of response (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.","definition_or_measurement_approach":"Time from first documented PR or better to first documented progression or death"}
  • {"endpoint_text":"- Part 2 (Cohort Expansion): Progression-free survival (PFS) as assessed by investigator, defined as time from start of treatment (for nonrandomized cohorts) or date of randomization (for randomized cohorts [Part 2 Cohorts 3, 4, and 5]) to the first documentation of disease progression or death, whichever occurs first.","definition_or_measurement_approach":"Time from treatment start or randomization to first documented progression or death"}
  • {"endpoint_text":"- Part 2 (Cohort Expansion): Overall survival (OS), defined as the time from start of treatment (for nonrandomized cohorts) or date of randomization (for randomized cohorts [Part 2 Cohorts 3, 4, and 5]) to the date of death due to any cause.","definition_or_measurement_approach":"Time from treatment start or randomization to death from any cause"}

Recruitment

Planned Sample Size
141
Recruitment Window Months
36
Consent Approach
Informed consent is obtained using subject information and informed consent forms (multiple L1/L2 ICF documents listed). Language- and country-specific ICFs are provided (documents available in multiple languages / country-specific versions are listed in the documents section). Trial excludes paediatric subjects; consent obtained from adult participants. (No detailed assent procedure for minors is provided.)

Geography

Total Number Of Sites
19
Total Number Of Participants
70

Germany

Earliest CTIS Part Ii Submission Date
18-03-2024
Latest Decision Or Authorization Date
24-03-2026
Processing Time Days
736
Number Of Sites
4
Number Of Participants
15

Sites

Site Name
Universitaetsklinikum Wuerzburg AöR
Department Name
Medical Clinic and Polyclinic II, Department of Hematology and Oncology
Contact Person Name
Leo Rasche
Contact Person Email
xxx@ukw.de
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Internal Medicine II, Oncological Clinical Trials Center
Contact Person Name
Katja Weisel
Contact Person Email
xxx@uke.de
Site Name
Universitaetsklinikum Aachen AöR
Department Name
Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation
Contact Person Name
Deniz Nogueira Gezer
Contact Person Email
xxx@ukaachen.de
Site Name
Technische Universitat Dresden
Department Name
Medical Clinic and Polyclinic I
Contact Person Name
Karolin Trautmann-Grill
Contact Person Email
xxx@ukdd.de

Spain

Earliest CTIS Part Ii Submission Date
27-03-2024
Latest Decision Or Authorization Date
27-03-2026
Processing Time Days
730
Number Of Sites
4
Number Of Participants
18

Sites

Site Name
Hospital Clinic De Barcelona
Department Name
Hematology
Contact Person Name
Laura Rosiñol
Contact Person Email
LROSINOL@clinic.cat
Site Name
Hospital Universitario Virgen De La Victoria
Department Name
Hematology
Contact Person Name
Ricarda Garcia
Contact Person Email
ricarda_g@yahoo.es
Site Name
Hospital San Pedro De Alcantara
Department Name
Hematology
Contact Person Name
Ignacio Casas
Contact Person Email
ignacio.casas@salud-juntaex.es
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Hematology
Contact Person Name
Estrella Carrillo
Contact Person Email
estrellacarrillocruz@gmail.com

Greece

Earliest CTIS Part Ii Submission Date
18-12-2023
Latest Decision Or Authorization Date
27-03-2026
Processing Time Days
830
Number Of Sites
2
Number Of Participants
7

Sites

Site Name
University General Hospital Of Alexandroupoli
Department Name
Hematology Department
Contact Person Name
Ioannis Kotsianidis
Contact Person Email
ikotsian@med.duth.gr
Site Name
Alexandra Hospital
Department Name
Plasma Cell Dyscrasias Unit, Department of Clinical Therapeutics
Contact Person Name
Maria Gavriatopoulou
Contact Person Email
mgavria@med.uoa.gr

Italy

Earliest CTIS Part Ii Submission Date
04-03-2024
Latest Decision Or Authorization Date
25-03-2026
Processing Time Days
751
Number Of Sites
6
Number Of Participants
21

Sites

Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Hematology Unit
Contact Person Name
Claudio Cerchione
Contact Person Email
claudio.cerchione@irst.emr.it
Site Name
Azienda Ospedaliero Universitaria Delle Marche
Department Name
Internal Medicine Department
Contact Person Name
Massimo Offidani
Site Name
University Hospital Consorziale Policlinico
Department Name
U.O.Ematologia con Trapianto
Contact Person Name
Pellegrino Musto
Site Name
Istituto Di Candiolo Fondazione Del Piemonte Per Loncologia IRCCS
Department Name
Oncologia Medica S.C. di Ematologia
Contact Person Name
Delia Rota Scalabrini
Contact Person Email
delia.rotascalabrini@ircc.it
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
Dipartimento Malattie Oncologiche ed Ematologiche
Contact Person Name
Elena Zamagni
Contact Person Email
e.zamagni@unibo.it
Site Name
European Institute Of Oncology S.r.l.
Department Name
Oncohematology Department
Contact Person Name
Enrico Derenzini
Contact Person Email
enrico.derenzini@ieo.it

France

Earliest CTIS Part Ii Submission Date
15-03-2024
Latest Decision Or Authorization Date
03-04-2026
Processing Time Days
749
Number Of Sites
3
Number Of Participants
9

Sites

Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Maladies du sang
Contact Person Name
Salomon Manier
Contact Person Email
xxx@xxx.xx
Site Name
Centre Hospitalier Universitaire De Poitiers
Department Name
Hematology and cellular therapy
Contact Person Name
Xavier Leleu
Contact Person Email
xxx@xxx.xx
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Hematology
Contact Person Name
Cyrille Touzeau
Contact Person Email
xxx@xxx.xx

Sponsor

Primary sponsor

Full Name
BeOne Medicines AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
Icon Public Limited Company
Responsibilities
sponsorDuties codes: [1,2,5]
Name
PRA Hellas CRO A.E.
Responsibilities
sponsorDuties codes: [1,2,6]
Name
Iqvia Biotech LLC
Responsibilities
sponsorDuties codes: [1,2,5]
Name
PPD (UK) Limited
Responsibilities
sponsorDuties codes: [8]
Name
Iqvia Laboratories Limited
Responsibilities
sponsorDuties codes: [4]

Third parties

  • {"country":"Singapore","full_name":"Almac Pharmaceutical Services Pte Ltd","duties_or_roles":"sponsorDuties codes: [3]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"sponsorDuties codes: [15], value: Reimbursement of patient expenses","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Hematogenix Laboratory Services Limited","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"China","full_name":"Sequanta Technologies Co. Ltd.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon Public Limited Company","duties_or_roles":"sponsorDuties codes: [1,2,5]","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"PPD (UK) Limited","duties_or_roles":"sponsorDuties codes: [8]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Iqvia Biotech LLC","duties_or_roles":"sponsorDuties codes: [1,2,5]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Abbott Molecular Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"China","full_name":"Wuxi Apptec Co. Ltd.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Beone Medicines USA Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"China","full_name":"Amoydx Biotechnology Research Center Co. Ltd.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Thermo Fisher Scientific Cork Limited","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
  • {"country":"Greece","full_name":"PRA Hellas CRO A.E.","duties_or_roles":"sponsorDuties codes: [1,2,6]","organisation_type":"Pharmaceutical company"}
  • {"country":"China","full_name":"Sequanta Technologies Co. Ltd.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
BGB-11417
Active Substance
N-[4-({[(1R,4R)-4-HYDROXY-4-METHYLCYCLOHEXYL]METHYL}AMINO)-3-NITROBENZENE-1-SULFONYL]-4-(2-{(2S)-2-[2-(PROPAN-2-YL)PHENYL]PYRROLIDIN1-YL}-7-AZASPIRO[3.5]NONAN-7-YL)-2-[(1H-PYRROLO[2,3-B]PYRIDIN-5-YL)OXY]BENZAMIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
prodAuthStatus: 1
Investigational Product Name
DARZALEX 1800 mg solution for injection
Active Substance
Daratumumab
Modality
Monoclonal antibody
Routes Of Administration
SUBCUTANEOUS USE
Route
SUBCUTANEOUS
Authorisation Status
prodAuthStatus: 2
Orphan Designation
Yes
Maximum Dose
1800 mg (product name)
Investigational Product Name
BGB-11417 (sponsor product code entry)
Active Substance
BGB-11417 (as above)
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
prodAuthStatus: 1
Investigational Product Name
DEXAMETHASONE
Active Substance
Dexamethasone acetate
Modality
Small molecule
Routes Of Administration
ORAL AND IV
Route
ORAL and IV
Authorisation Status
prodAuthStatus: 2 (scientific product entry)
Investigational Product Name
Kyprolis 60 mg powder for solution for infusion
Active Substance
Carfilzomib
Modality
Small molecule
Routes Of Administration
INTRAVENIOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
prodAuthStatus: 2
Orphan Designation
Yes
Maximum Dose
60 mg (product name)
Combination Treatment
Yes

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