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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04091126




Registration number
NCT04091126
Ethics application status
Date submitted
13/09/2019
Date registered
16/09/2019
Date last updated
15/09/2020

Titles & IDs
Public title
Study of Belantamab Mafodotin Plus Standard of Care (SoC) in Newly Diagnosed Multiple Myeloma
Scientific title
A Phase 1, Randomized, Dose and Schedule Evaluation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Belantamab Mafodotin Administered in Combination With Standard of Care in Participants With Newly Diagnosed Multiple Myeloma
Secondary ID [1] 0 0
209664
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Belantamab mafodotin
Treatment: Drugs - Bortezomib
Treatment: Drugs - Lenalidomide
Treatment: Drugs - Dexamethasone

Experimental: Cohort 1: belantamab mafodotin 1.9 mg/kg Q3/4W + VRd/Rd - Participants will receive 1.9 milligram /kilogram (mg/kg) three -weekly (Q3W) dose of belantamab mafodotin intravenously (IV) on Day 1 of every 21-day cycle for the first 8 cycles in combination with VRd. From cycle 9 onwards, participants will receive 1.9 mg/kg four-weekly (Q4W) dose of belantamab mafodotin intravenously on Day 1 of every 28-day cycle in combination with Rd.

Experimental: Cohort 2: belantamab mafodotin 1.4 mg/kg Q6/8W + VRd/Rd - Participants will receive 1.4 mg/kg six-weekly (Q6W) dose of belantamab mafodotin intravenously on Day 1 of every other 21-day cycle for the first 8 cycles in combination with VRd. From cycle 9 onwards, participants will receive 1.4 mg/kg eight-weekly (Q8W) dose of belantamab mafodotin intravenously on Day 1 of every other 28-day cycle in combination with Rd.

Experimental: Cohort 3: belantamab mafodotin 1.9 mg/kg Q6/8W + VRd/Rd - Participants will receive 1.9 mg/kg Q6W dose of belantamab mafodotin intravenously on Day 1 of every other 21-day cycle for the first 8 cycles in combination with VRd. From cycle 9 onwards, participants will receive 1.9 mg/kg Q8W dose of belantamab mafodotin intravenously on Day 1 of every other 28-day cycle in combination with Rd.

Experimental: Cohort 4: belantamab mafodotin 1.0 mg/kg Q3/4W + VRd/Rd - Participants will receive 1.0 mg/kg Q3W dose of belantamab mafodotin intravenously on Day 1 of every 21-day cycle for the first 8 cycles in combination with VRd. From cycle 9 onwards, participants will receive 1.0 mg/kg Q4W dose of belantamab mafodotin intravenously on Day 1 of every 28-day cycle in combination with Rd.

Experimental: Cohort 5: belantamab mafodotin 1.4 mg/kg Q3/4W + VRd/Rd - Participants will receive 1.4 mg/kg Q3W dose of belantamab mafodotin intravenously on Day 1 of every 21-day cycle for the first 8 cycles in combination with VRd. From cycle 9 onwards, participants will receive 1.4 mg/kg Q4W dose of belantamab mafodotin intravenously on Day 1 of every 28-day cycle in combination with Rd.

Experimental: Cohort 6: belantamab mafodotin 1.9 or 2.5 mg/kg Q9/12W+VRd/Rd - Based on emerging data, participants will receive either 1.9 mg/kg or 2.5 mg/kg Q9W dose of belantamab mafodotin intravenously on Day 1 of every third 21-day cycle for the first 8 cycles in combination with VRd. From cycle 9 onwards, participants will receive either 1.9 mg/kg or 2.5 mg/kg Q12W dose of belantamab mafodotin intravenously on Day 1 of every third 28-day cycle in combination with Rd.

Experimental: Cohort7:belantamab mafodotin 1.9/2.5mg/kg Q6/8W (split)+VRd/Rd - Based on emerging data, participants will receive a total dose of either 1.9 mg/kg or 2.5 mg/kg of belantamab mafodotin intravenously (split in to two equal doses of 0.95 mg/kg or 1.25 mg/kg to be given on Day 1 and Day 8) Q6W of every other 21-day cycle for the first 8 cycles in combination with VRd. From cycle 9 onwards, participants will receive a total dose of either 1.9 mg/kg or 2.5 mg/kg of belantamab mafodotin intravenously (split in to two equal doses of 0.95 mg/kg or 1.25 mg/kg to be given on Day 1 and Day 8) Q8W of every other 28-day cycle in combination with Rd.

Experimental: Cohort 8: belantamab mafodotin 2.5 mg/kg Q6/8W + VRd/Rd - Based on emerging data, participants will receive 2.5 mg/kg Q6W dose of belantamab mafodotin intravenously on Day 1 of every other 21-day cycle for the first 8 cycles in combination with VRd. From cycle 9 onwards, participants will receive 2.5 mg/kg Q8W dose of belantamab mafodotin intravenously on Day 1 of every other 28-day cycle in combination with Rd.


Treatment: Drugs: Belantamab mafodotin
Selected doses of belantamab mafodotin will be administered as intravenous infusion.

Treatment: Drugs: Bortezomib
Bortezomib will be administered subcutaneously or intravenously 1 hour after the belantamab mafodotin infusion.

Treatment: Drugs: Lenalidomide
Lenalidomide will be administered as 25 or 10 mg orally, depending upon renal function.

Treatment: Drugs: Dexamethasone
Dexamethasone will be administered orally as 20 mg in cycles 1-8 and 40 mg in Cycle 9 onwards.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with dose-limiting toxicities (DLTs) - The number of participants with DLTs will be reported.
Timepoint [1] 0 0
Treatment cycle 1 to 3 (each cycle of 21 days)
Primary outcome [2] 0 0
Number of participants with adverse events (AEs) and serious adverse events (SAEs) - AEs and SAEs will be collected.
Timepoint [2] 0 0
Up to an average of 54 months
Secondary outcome [1] 0 0
Lenalidomide relative dose intensity (RDI ) of treatment with belantamab mafodotin in combination with VRd - RDI of treatment with belantamab mafodotin in combination with VRd will be analyzed.
Timepoint [1] 0 0
4 treatment cycles (each cycle of 21 days)
Secondary outcome [2] 0 0
Bortezomib RDI of treatment with belantamab mafodotin in combination with VRd - RDI of treatment with belantamab mafodotin in combination with VRd will be analyzed.
Timepoint [2] 0 0
4 treatment cycles (each cycle of 21 days)
Secondary outcome [3] 0 0
Cumulative administered dose of belantamab mafodotin treatment in combination with VRd - Cumulative administered dose of belantamab mafodotin in treatment in combination with VRd will be analyzed.
Timepoint [3] 0 0
4 treatment cycles (each cycle of 21 days)
Secondary outcome [4] 0 0
Maximum plasma concentration (Cmax) of belantamab mafodotin - Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Timepoint [4] 0 0
Up to an average of 52 months
Secondary outcome [5] 0 0
Cmax of total monoclonal antibody (mAb) - Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Timepoint [5] 0 0
Up to an average of 52 months
Secondary outcome [6] 0 0
Cmax of microtubule inhibitor monomethyl auristatin-F with a cysteine linker (cys-mcMMAF) - Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Timepoint [6] 0 0
Up to an average of 52 months
Secondary outcome [7] 0 0
Area under the concentration time curve (AUC) of belantamab mafodotin - Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Timepoint [7] 0 0
Up to an average of 52 months
Secondary outcome [8] 0 0
AUC of monoclonal antibody (mAb) - Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Timepoint [8] 0 0
Up to an average of 52 months
Secondary outcome [9] 0 0
AUC of cys-mcMMAF - Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Timepoint [9] 0 0
Up to an average of 52 months
Secondary outcome [10] 0 0
Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin - Serum samples for the analysis of anti-belantamab mafodotin antibodies will be collected. The samples will be tested for anti-belantamab mafodotin antibodies using a tiered-testing scheme consisting of validated screening, confirmation, and titration assays.
Timepoint [10] 0 0
Up to an average of 52 months
Secondary outcome [11] 0 0
Titers of ADAs against belantamab mafodotin - Serum samples for the analysis of anti-belantamab mafodotin antibodies will be collected. The samples will be tested for anti-belantamab mafodotin antibodies using a tiered-testing scheme consisting of validated screening, confirmation, and titration assays.
Timepoint [11] 0 0
Up to an average of 52 months
Secondary outcome [12] 0 0
Overall Response Rate (ORR) - ORR is defined as the percentage of participants with a confirmed partial response (PR) or better based on the response assessed by the investigator using International Myeloma Working Group (IMWG) criteria.
Timepoint [12] 0 0
Up to 52 months
Secondary outcome [13] 0 0
Complete Response Rate (CRR) - CRR is defined as the percentage of participants with a confirmed complete response (CR) or better based on the response assessed by the investigator using IMWG criteria.
Timepoint [13] 0 0
Up to 52 months
Secondary outcome [14] 0 0
Rate of Very Good Partial Response (VGPR) or better - Rate of VGPR or better is defined as the percentage of participants with a confirmed VGPR or better based on the response assessed by the investigator using IMWG criteria.
Timepoint [14] 0 0
Up to 52 months

Eligibility
Key inclusion criteria
- Participant must be over 18 years of age inclusive, at the time of signing the
informed consent.

- Diagnosis of multiple myeloma with a requirement for treatment as documented per
international myeloma working group (IMWG) criteria.

- Must have at least one aspect of measurable disease, defined as one of the following:

- Urine M-protein excretion >=200 mg/24 hours (>=0.2 gram [g]/24 hours), or

- Serum M-protein concentration >=0.5 grams per deciliter (g/dL) (>=5.0 gram per liter
[g/L]), or

- Serum free light chain (FLC) assay: involved FLC level >=10 milligrams per deciliter
(mg/dL) (>=100 milligram per liter [mg/L]) and an abnormal serum free light chain
ratio (<0.26 or >1.65).

- Not a candidate for high-dose chemotherapy with autologous stem cell transplant (ASCT)
due to presence of significant comorbid condition(s), such as cardiac, pulmonary or
other major organ dysfunction that are likely to have a negative impact on
tolerability of high dose chemotherapy with stem cell transplantation, as judged by
the investigator.

- Eastern cooperative oncology group (ECOG) status of 0-2

- Adequate organ system functions as defined by the laboratory assessments listed as
following: Absolute neutrophil count (ANC) >=1.5 x 10^9/L; Hemoglobin >=8.0 g/dL;
Platelets >=75 x 10^9/L; Total bilirubin <=1.5 x upper limit of normal (ULN);
(Isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct
bilirubin is <35%); Alanine aminotransferase (ALT) <=2.5 x ULN; eGFR >=30
mL/minute/1.73 meter^2; Urine Dipstick for protein OR Albumin/creatinine ratio (from
spot urine)- Negative/trace (if >=1 plus only eligible if confirmed <=500 mg/gram (56
mg/millimoles [mmol]) by albumin/creatinine ratio (spot urine from first void); Left
Ventricular Ejection Fraction (LVEF) by echocardiogram (ECHO) of >=35% participants
with low LVEF (per institutional standards), consider referring to cardiology per
local standards of care.

- Male and/or female

- Contraceptive use by women should be consistent with local regulations regarding the
methods of contraception for those participating in clinical studies. A female
participant is eligible to participate if she is not pregnant or breastfeeding, and at
least 1 of the following conditions applies:

- Is NOT a woman of childbearing potential (WOCBP) or Due to lenalidomide being a
thalidomide analogue with risk for embryofetal toxicity and prescribed under a
pregnancy prevention/controlled distribution program, and bortezomib having the
potential to cause fetal harm, WOCBP participants will be eligible if they commit to
either: abstain continuously from heterosexual sexual intercourse as their preferred
and usual lifestyle (abstinent on a long term and persistent basis) and agree to
remain abstinent OR to use birth control as follows: Two methods of reliable birth
control (one method that is highly effective and one additional effective (barrier)
method), beginning 4 weeks prior to initiating treatment with lenalidomide, during
therapy, during dose interruptions and continuing for 4 weeks following
discontinuation of lenalidomide treatment. Thereafter, WOCBP participants must use one
method of reliable birth control that is highly effective for a further 3 months
following discontinuation of belantamab mafodotin, or a further 6 months following
discontinuation of bortezomib, whichever is longer. WOCBP must also agree not to
donate eggs (ova, oocytes) for the purpose of reproduction during treatment, during
dose interruptions and for 28-days following the last dose of lenalidomide, 4 months
following discontinuation of belantamab mafodotin treatment or 7-months following the
last dose of bortezomib, whichever is longer. Two negative pregnancy tests must be
obtained prior to initiating therapy. The first test should be performed within 10-14
days and the second test within 24 hours prior to prescribing the start of
lenalidomide therapy.

The participant should not receive lenalidomide until the investigator has verified that
the results of these pregnancy tests are negative. The investigator should evaluate the
effectiveness of the contraceptive method in relationship to the first dose of study
intervention. The Investigator is responsible for review of medical history, menstrual
history, and recent sexual activity to decrease the risk for inclusion of a woman with an
early undetected pregnancy.

- Contraceptive use by men should be consistent with local regulations regarding the
methods of contraception for those participating in clinical studies

- Male participants are eligible to participate if they agree to the following from the
time of first dose of study treatment until 28-days after the last dose of
lenalidomide, 4-months after the last dose of bortezomib, or 6 months after the last
dose of belantamab mafodotin, whichever is longer, to allow for clearance of any
altered sperm: Refrain from donating sperm - Plus either: - Be abstinent from
heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long
term and persistent basis) and agree to remain abstinent OR Must agree to use
contraception/barrier as detailed below: Agree to use a male condom, even if they have
undergone a successful vasectomy, and female partner to use an additional highly
effective contraceptive method with a failure rate of <1% per year when having sexual
intercourse with a WOCBP. Male participants should also use a condom when having
sexual intercourse with pregnant females.

- Capable of giving signed informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Smoldering multiple myeloma (SMM).

- Prior systemic therapy for multiple myeloma, or SMM. NOTE: An emergency course of
steroids (defined as no greater than 40 mg of dexamethasone, or equivalent per day for
a maximum of 4 days (that is, a total of 160 mg) is permitted. NOTE: Focal palliative
radiation is permitted prior to enrollment, provided that it occurred at least 2 weeks
prior to the first dose of study drug, that the participant has recovered from
radiation-related toxicities, and that the participant did not require corticosteroids
for radiation-induced adverse events.

- Participant is eligible for high dose chemotherapy with ASCT, as determined by a
frailty score of 0 as assessed by the IMWG frailty index.

- Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the
national cancer institute (NCI)-common terminology criteria for adverse events (CTCAE)
Version 5.

- Major surgery within 4 weeks prior to the first dose of study drug.

- Presence of active renal condition (infection, requirement for dialysis or any other
significant condition that could affect participant's safety). Participants with
isolated proteinuria resulting from multiple myeloma (MM) are eligible, provided they
fulfil criteria.

- Any serious and/or unstable pre-existing medical, psychiatric disorder or other
conditions (including lab abnormalities) that could interfere with participant's
safety, obtaining informed consent or compliance to the study procedures.

- Evidence of active mucosal or internal bleeding uncontrolled by local therapy and not
explained by reversible coagulopathy.

- Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic
gallstones, or otherwise stable chronic liver disease as per the Investigator's
assessment).

- Participants with previous or concurrent malignancies other than multiple myeloma are
excluded. Exceptions are surgically treated cervical carcinoma in situ, or any other
malignancy that has been considered medically stable for at least 2 years. The
participant must not be receiving active therapy, other than hormonal therapy for this
disease. Note: Participants with curatively treated non-melanoma skin cancer are
allowed without a 2-year restriction.

- Evidence of cardiovascular risk including any of following: Evidence of current
clinically significant untreated arrhythmias, including clinically significant
electrocardiogram (ECG) abnormalities including second degree (Mobitz Type II) or
third degree atrioventricular (AV) block; History of myocardial infarction, acute
coronary syndromes (including unstable angina), coronary angioplasty, or stenting or
bypass grafting within 3 months of Screening.; Class III or IV heart failure as
defined by the New York Heart Association (NYHA) functional classification system;
Uncontrolled hypertension.

- Active infection requiring treatment.

- Known human immunodeficiency virus (HIV) infection.

- Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb),
at Screening or within 3 months prior to first dose of study treatment. Note:
Participants with positive hepatitis C antibody due to prior resolved disease can be
enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.

- Positive hepatitis C antibody test result.

- Current corneal epithelial disease except for mild punctate keratopathy. Note:
Participants with mild punctate keratopathy are allowed.

- Intolerance or contraindications to anti-viral prophylaxis.

- Unable to tolerate antithrombotic prophylaxis.

- AL amyloidosis (light chain amyloidosis), active polyneuropathy, organomegaly,
endocrinopathy, monoclonal plasma proliferative disorder, skin changes (POEMS)
syndrome or active plasma cell leukemia at the time of screening.

- Exhibiting clinical signs of or has a known history of meningeal or central nervous
system involvement by multiple myeloma.

- Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to
drugs chemically related to belantamab mafodotin, or any of the components of the
study treatment.

- Use of an investigational drug within 14 days or five half-lives (whichever is longer)
preceding the first dose of study drug.

- Plasmapheresis within 7 days prior to the first dose of study drug.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Waratah
Recruitment hospital [2] 0 0
GSK Investigational Site - Clayton
Recruitment hospital [3] 0 0
GSK Investigational Site - Fitzroy
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Kansas
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Wisconsin
Country [4] 0 0
Canada
State/province [4] 0 0
Alberta
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
France
State/province [6] 0 0
Nantes cedex 1
Country [7] 0 0
France
State/province [7] 0 0
Rennes cedex 9
Country [8] 0 0
Germany
State/province [8] 0 0
Baden-Wuerttemberg
Country [9] 0 0
Germany
State/province [9] 0 0
Mecklenburg-Vorpommern
Country [10] 0 0
Germany
State/province [10] 0 0
Hamburg
Country [11] 0 0
Italy
State/province [11] 0 0
Emilia-Romagna
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Seoul, Korea
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Seoul
Country [14] 0 0
Spain
State/province [14] 0 0
Barcelona
Country [15] 0 0
Spain
State/province [15] 0 0
Madrid
Country [16] 0 0
Spain
State/province [16] 0 0
Pamplona
Country [17] 0 0
Spain
State/province [17] 0 0
Pozuelo De Alarcón/Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity
of belantamab mafodotin in combination with Velcade (bortezomib), Revlimid (lenalidomide),
dexamethasone (VRd) and will determine recommended phase 3 dose (RP3D) in adult participants
with newly diagnosed multiple myeloma (NDMM). Participants will receive the combination of
bortezomib, lenalidomide and dexamethasone (VRd) on a 3-week cycle until cycle 8, followed by
the combination of lenalidomide and dexamethasone (Rd) on a 4-week cycle thereafter as per
dosing schedule. Participants will receive belantamab mafodotin on a schedule that is
dependent on the cohort to which they are assigned. This will be every cycle of VRd, every
other cycle of VRd, or every third cycle of VRd. Belantamab may also be given as a 'split'
dose, which is 50% of the dose on Day 1 and 50% of the dose on Day 8 of a cycle. Participants
will complete an End of Treatment (EOT) visit at the point of study treatment
discontinuation, followed by a Safety Follow-up visit 70 days after EOT.
Trial website
https://clinicaltrials.gov/show/NCT04091126
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04091126