Clinical trial NCT04484623: Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma
Official title: A Phase III, Multicenter, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Pomalidomide and Dexamethasone (B-Pd) Versus Pomalidomide Plus Bortezomib and Dexamethasone (PVd) in Participants With Relapsed/Refractory Multiple Myeloma (DREAMM 8)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Global Cohort
Belantamab Mafodotin
Relapsed/Refractory Multiple Myeloma
Pomalidomide
Dexamethasone
Bortezomib
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2020-07-23
Enrollment: 302
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone (Arm A) compared with that of combination of pomalidomide, bortezomib and dexamethasone (Arm B) in participants with relapsed/refractory multiple myeloma (RRMM).


Eligibility criteria: Inclusion Criteria:

* Capable of giving signed informed consent.
* Male or female, 18 years or older.
* Have a confirmed diagnosis of multiple myeloma (MM) as defined by the International Myeloma Working Group (IMWG) criteria.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Have been previously treated with at least 1 prior line of MM therapy including a lenalidomide-containing regimen and must have documented disease progression during or after their most recent therapy. (Participants treated with lenalidomide ≥10 mg daily for at least 2 consecutive cycles are eligible).
* Must have at least 1 aspect of measurable disease defined as one of the following;

  1. Urine M-protein excretion greater than or equal to (≥)200 milligrams (mg) per 24-hour, or
  2. Serum M-protein concentration ≥0.5 grams/deciliters (g/dL) (≥5.0 g/liter \[L\]), or
  3. Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (less than \[\<\]0.26 or greater than \[\>\]1.65) only if participant has no measurable urine or serum M spike.
* Have undergone autologous stem cell transplant (ASCT) or are considered transplant ineligible. Participants with a history of ASCT are eligible for study participation provided the following eligibility criteria are met: a. ASCT was \>100 days prior to the first dose of study medication. b. No active bacterial, viral, or fungal infection(s) present
* All prior treatment-related toxicities (defined by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] version 5.0) must be less than or equal to (≤)Grade 1 at the time of enrolment, except for alopecia.
* Adequate organ system functions as mentioned in the protocol.
* Male and female participants agree to abide by protocol-defined contraceptive requirements.

Exclusion Criteria:

* Active plasma cell leukemia, symptomatic amyloidosis or active polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, and skin changes (POEMS) syndrome at the time of screening.
* Prior allogeneic SCT.
* Systemic anti-myeloma therapy (including chemotherapy and systemic steroids) within 14 days or five half-lives (whichever is shorter) preceding the first dose of study drug; prior treatment with a monoclonal antibody drug within 30 days of receiving the first dose of study drugs.
* Plasmapheresis within 7 days prior to the first dose of study drug.
* Received prior treatment with or intolerant to pomalidomide.
* Received prior Beta cell maturation antigen (BCMA) targeted therapy.
* Intolerant to bortezomib or refractory to bortezomib (for example; participant experienced progressive disease during treatment, or within 60 days of completing treatment, with a bortezomib-containing regimen of 1.3 mg/meter square \[m\^2\] twice weekly).
* Evidence of cardiovascular risk including any of the following;

  1. Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram abnormalities including second degree (Mobitz type II) or third degree atrioventricular (AV) block.
  2. Recent history within (3 months of screening) of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting .
  3. Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
  4. Uncontrolled hypertension.
* Any major surgery within the last 4 weeks.
* Previous or concurrent invasive malignancy other than multiple myeloma, except:

  1. The disease must be considered medically stable for at least 2 years; or
  2. The participant must not be receiving active therapy, other than hormonal therapy for this disease.
* Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
* Evidence of active mucosal or internal bleeding.
* Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice.
* Active infection requiring treatment.
* Known or active human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C will be excluded unless the protocol-defined criteria are met.
* Presence of active renal conditions (such as infection, severe renal impairment requiring dialysis or any other condition that could affect participant's safety).
* Ongoing Grade 2 peripheral neuropathy with pain within 14 days prior to randomization or ≥Grade 3 peripheral neuropathy.
* Active or history of venous and arterial thromboembolism within the past 3 months.
* Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis.
* Current corneal disease except for mild punctate keratopathy.
* Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
* Pregnant or lactating female.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 174 weeks
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 473 weeks
measure: Duration of Response (DoR)
timeFrame: Up to approximately 473 weeks
measure: Minimal Residual Disease (MRD) Negativity Rate
timeFrame: Up to approximately 473 weeks
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 473 weeks
measure: Complete Response Rate (CRR)
timeFrame: Up to approximately 473 weeks
measure: Percentage of Participants With a Confirmed Very Good Partial Response (VGPR) or Better
timeFrame: Up to approximately 473 weeks
measure: Time to Best Response (TTBR)
timeFrame: Up to approximately 473 weeks
measure: Time to Response (TTR)
timeFrame: Up to approximately 473 weeks
measure: Time to Progression (TTP)
timeFrame: Up to approximately 473 weeks
measure: Progression-Free Survival 2 (PFS2)
timeFrame: Up to approximately 473 weeks
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 473 weeks
measure: Number of Participants With Clinically Significant Changes in Hematology Parameters
timeFrame: Up to approximately 473 weeks
measure: Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters
timeFrame: Up to approximately 473 weeks
measure: Number of Participants With Abnormal Ocular Findings on Ophthalmic Examination
timeFrame: Up to approximately 473 weeks
measure: Plasma Concentrations of Belantamab Mafodotin (ADC) at Indicated Time Points
timeFrame: Up to approximately 473 weeks
measure: Plasma Concentrations of Monomethyl Auristatin-F With a Cysteine Linker (Cys-mcMMAF) at Indicated Time Points
timeFrame: Up to approximately 473 weeks
measure: Area Under Plasma Concentration-time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (C(Tlast)) [AUC (0-last)] for Pomalidomide
timeFrame: Up to approximately 473 weeks
measure: Area Under Plasma Concentration-time Curve (AUC) From Time 0 to End of the Dosing Interval [AUC (0-tau)] for Pomalidomide
timeFrame: Up to approximately 473 weeks
measure: Maximum Concentration (Cmax) for Pomalidomide
timeFrame: Up to approximately 473 weeks
measure: Time of Cmax (Tmax) for Pomalidomide
timeFrame: Up to approximately 473 weeks
measure: Trough Concentration Prior to the Next Dose for Each Cycle (Ctrough) for Pomalidomide
timeFrame: Up to approximately 473 weeks
measure: Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) for Pomalidomide
timeFrame: Up to approximately 473 weeks
measure: Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin
timeFrame: Up to approximately 473 weeks
measure: Titers of ADAs Against Belantamab Mafodotin
timeFrame: Up to approximately 473 weeks
measure: Number of Participants With Maximum Post-baseline Change From Baseline in Individual Items of Patient-Reported Outcome Version of the Common Term Criteria for Adverse Events (PRO-CTCAE)
timeFrame: Up to approximately 473 weeks
measure: Change From Baseline in Health Related Quality of Life (HRQoL) as Measured by EuropeanOrganization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30)
timeFrame: Up to approximately 473 weeks
measure: Change From Baseline in Quality of Life Questionnaire 20-item Multiple Myeloma Module (QLQMY20)
timeFrame: Up to approximately 473 weeks
measure: Change From Baseline in HRQoL as Measured by EORTC IL52
timeFrame: Up to approximately 473 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Fort Myers
country: United States
facility: GSK Investigational Site
state: Florida
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Kansas City
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state: Missouri
city: Nashville
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state: Tennessee
city: Garran
country: Australia
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state: Australian Capital Territory
city: Darlinghurst
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facility: GSK Investigational Site
state: New South Wales
city: Gosford NSW
country: Australia
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state: New South Wales
city: Port Macquarie
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city: South Brisbane
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city: Adelaide
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city: Nedlands
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country: Greece
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country: Korea, Republic of
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country: Korea, Republic of
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city: Seoul
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Auckland
country: New Zealand
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city: Dunedin
country: New Zealand
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city: Grafton
country: New Zealand
facility: GSK Investigational Site
city: Hamilton
country: New Zealand
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city: Takapuna Auckland
country: New Zealand
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city: Tauranga
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city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Gdansk
country: Poland
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country: Poland
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country: Poland
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country: Poland
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Novosibirsk
country: Russian Federation
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city: Saint Petersburg
country: Russian Federation
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city: Samara
country: Russian Federation
facility: GSK Investigational Site
city: Sochi
country: Russian Federation
facility: GSK Investigational Site
city: St Petersburg
country: Russian Federation
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city: St-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Barcelona
country: Spain
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city: Barcelona
country: Spain
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city: Gijon
country: Spain
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city: L'Hospitalet De Llobrega
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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city: MOstoles Madrid
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city: Murcia
country: Spain
facility: GSK Investigational Site
city: Palma de Mallorca
country: Spain
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city: PamplonaNavarra
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country: Spain
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country: Turkey
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city: Ankara
country: Turkey
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city: Ankara
country: Turkey
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city: Izmir
country: Turkey
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city: Izmir
country: Turkey
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city: Kocaeli
country: Turkey
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city: Mersin
country: Turkey
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city: Samsun
country: Turkey
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city: London
country: United Kingdom
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city: Plymouth
country: United Kingdom
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city: Southampton
country: United Kingdom
facility: GSK Investigational Site
city: Stoke on Trent
country: United Kingdom
facility: GSK Investigational Site
city: Sutton
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: