An Open-label, Dose Escalation Study in Japanese Participants With Relapsed/Refractory Multiple Myeloma Who Have Failed Prior Anti Myeloma Treatments

NCT03828292 | Completed Phase 1 Results

• 1 other identifier: 207504
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

Brief Summary

Belantamab mafodotin (GSK2857916) is a first in class, antibody dependent cellular cytotoxicity (ADCC) enhanced, humanized immunoglobulin G1 (IgG1) antibody-drug conjugate (ADC) which binds specifically to B cell maturation antigen (BCMA) expressed on tumor cells of all participants with multiple myeloma. This is a Phase 1, open label, dose escalation study to investigate safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and clinical activity of GSK2857916 when given as monotherapy (Part 1) or given as combination therapy (Part 2). Dose escalation will follow a 3+3 design.

Conditions

Multiple Myeloma

Keywords

Antibody drug conjugate; Dose-escalation; GSK2857916; Japanese; Relapsed/Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (29)

• Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT is an Adverse Event (AE) that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21-day DLT period and meets at least one of the DLT criteria: Grade 3 or greater febrile neutropenia lasting \>48 hours (h) despite adequate treatment, Grade 4 thrombocytopenia \<25,000/mm\^3accompanied by clinically significant bleeding, any Grade 3 or greater non-hematologic toxicity, any Grade 3 or greater non-hematologic laboratory value if: laboratory abnormality persists for \>48 h despite supportive treatment for abnormality leads to hospitalization, Grade 4 Corneal toxicity, and liver toxicity meeting pre-specified GlaxoSmithKline liver stopping criteria. DLTs were assessed by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03.

  Up to Day 21

• Part 2: Arm A: Number of Participants With DLTs

  DLT is an AE that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21-day DLT period and meets at least one of the DLT criteria: Grade 3 or greater febrile neutropenia lasting \>48 hours (h) despite adequate treatment, Grade 4 thrombocytopenia \<25,000/mm\^3 accompanied by clinically significant bleeding, any Grade 3 or greater non-hematologic toxicity, any Grade 3 or greater non-hematologic laboratory value if: laboratory abnormality persists for \>48 h despite supportive treatment or abnormality leads to hospitalization, Grade 4 Corneal toxicity, and liver toxicity meeting pre-specified GlaxoSmithKline liver stopping criteria. DLTs were assessed by NCI-CTCAE, version 4.03.

  Up to Day 21

• Part 2: Arm B: Number of Participants With DLTs

  DLT is an AE that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21-day DLT period and meets at least one of the DLT criteria: Grade 3 or greater febrile neutropenia lasting \>48 hours (h) despite adequate treatment, Grade 4 thrombocytopenia \<25,000/mm\^3 accompanied by clinically significant bleeding, any Grade 3 or greater non-hematologic toxicity, any Grade 3 or greater non-hematologic laboratory value if: laboratory abnormality persists for \>48 h despite supportive treatment or abnormality leads to hospitalization, Grade 4 Corneal toxicity, and liver toxicity meeting pre-specified GlaxoSmithKline liver stopping criteria. DLTs were assessed by NCI-CTCAE, version 4.03.

  Up to Day 28

• Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect. SAEs are subset of AEs.

  Up to approximately 141 weeks

• Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent disability/incapacity or Is a congenital anomaly/birth defect other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs.

  Up to approximately 212 weeks

• Part 1: Number of Participants With Worst-case Grade Change From Baseline in Clinical Chemistry Parameters

  Blood samples were collected for clinical chemistry parameters analysis: Creatine Kinase (CK), Creatinine, Gamma Glutamyl Transferase (GGT), Magnesium, Phosphate, Potassium, Sodium, Calcium, Glucose, Urate, Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Bilirubin were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v) 4.03. Grade (G)1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 141 weeks

• Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters

  Blood samples were collected for analysis of clinical chemistry parameters: C Reactive Protein, Chloride, Direct Bilirubin (DB), Lactate Dehydrogenase, Protein and Urea. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE v4.03. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 141 weeks

• Part 2: Number of Participants With Worst-case Grade Change From Baseline in Clinical Chemistry Parameters

  Blood samples were collected for clinical chemistry parameters analysis: Creatine Kinase (CK), Creatinine, Gamma Glutamyl Transferase (GGT), Magnesium, Phosphate, Potassium, Sodium, Calcium, Glucose, Urate, Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Bilirubin were graded according to NCI-CTCAE v 4.03. G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 212 weeks

• Part 2: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters

  Blood samples were collected for analysis of clinical chemistry parameters: C Reactive Protein, Chloride, Direct Bilirubin (DB), Lactate Dehydrogenase, Protein and Urea. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE v4.03. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 212 weeks

• Part 1: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters

  Blood samples were collected for analysis of hematology parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils and Platelets were graded according to CTCAE v4.03. G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 141 weeks

• Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters

  Blood samples were collected for the analysis of following hematology parameters: Basophils, Eosinophils, Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Volume (MCV), erythrocytes, Hematocrit, monocytes and reticulocytes. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 141 weeks

• Part 2: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters

  Blood samples were collected for analysis of hematology parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils and Platelets were graded according to CTCAE v4.03. G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 212 weeks

• Part 2: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters

  Blood samples were collected for the analysis of following hematology parameters: Basophils, Eosinophils, MCHC, MCH, MCV, erythrocytes, Hematocrit, monocytes and reticulocytes. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. The number of participants with decreases to low, changes to normal or no changes, and increases to high from baseline values have been presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 212 weeks

• Part 1: Number of Participants With Worst-case Change in Post Baseline Values Relative to Baseline Urinalysis Results: Occult Blood and Protein

  Urine samples were collected to analyze presence of occult blood and protein in urine by dipstick method. Data for worst-case post baseline urinalysis results is presented. Result for urinalysis parameters were recorded as no change/decreased, Increase to SMALL, Increase to MODERATE, Increase to LARGE, and any increase including increase to +-, 1+, 2+, 3+, unknown indicating proportional concentrations in the urine sample.

  Baseline (Day 1) and up to approximately 141 weeks

• Part 2: Number of Participants With Worst-case Change in Post Baseline Values Relative to Baseline Urinalysis Results: Occult Blood and Protein

  Urine samples were collected to analyze presence of occult blood and protein in urine by dipstick method. Data for worst-case post baseline urinalysis results is presented. Result for urinalysis parameters were recorded as no change/decreased, Increase to SMALL, Increase to MODERATE, Increase to LARGE, and any increase including increase to +-, 1+, 2+, 3+, unknown indicating proportional concentrations in the urine sample.

  Baseline (Day 1) and up to approximately 212 weeks

• Part 1: Change From Baseline (CFB) in Urine Potential of Hydrogen (pH)

  Urine samples were collected to analyze urine pH levels. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 141 weeks

• Part 2: Change From Baseline in Urine Potential of Hydrogen (pH)

  Urine samples were collected to analyze urine pH levels. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 212 weeks

• Part 1: Change From Baseline in Urine Specific Gravity by Dipstick

  Urine samples were collected to analyze urine specific gravity. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 141 weeks

• Part 2: Change From Baseline in Urine Specific Gravity by Dipstick

  Urine samples were collected to analyze urine specific gravity. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 212 weeks

• Part 1: Number of Participants With Worst-case Grade Change Post-baseline in Vital Sign Parameters: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

  DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.03. For SBP: Grade (G) 0 (\<120 millimeter of mercury \[mmHg\]), G1 (120-139 mmHg), G2 (140-159 mmHg), G3 (\>=160 mmHg). For DBP: G0 (\<80 mmHg), G1 (80-89 mmHg), G2 (90-99 mmHg), G3 (\>=100 mmHg). Higher grade indicates greater severity. Data for participants with worst-case post baseline with any grade increase and a maximum post-baseline grade increase to G2 and G3 from their baseline grade are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 141 weeks

• Part 2: Number of Participants With Worst-case Grade Change Post-baseline in Vital Sign Parameters: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

  DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.03. For SBP: Grade (G) 0 (\<120 millimeter of mercury \[mmHg\]), G1 (120-139 mmHg), G2 (140-159 mmHg), G3 (\>=160 mmHg). For DBP: G0 (\<80 mmHg), G1 (80-89 mmHg), G2 (90-99 mmHg), G3 (\>=100 mmHg). Higher grade indicates greater severity. Data for participants with worst-case post baseline with any grade increase and a maximum post-baseline grade increase to G2 and G3 from their baseline grade are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 212 weeks

• Part 1: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Temperature

  Temperature was measured after resting for at least 5 minutes. The abnormal ranges for body temperature were (\<=35 degrees Celsius or \>=38 degrees Celsius). Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 141 weeks

• Part 2: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Temperature

  Temperature was measured after resting for at least 5 minutes. The abnormal ranges for body temperature were (\<=35 degrees Celsius or \>=38 degrees Celsius). Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 212 weeks

• Part 1: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Heart Rate

  Heart rate was measured after resting for at least 5 minutes. The abnormal ranges for heart rate were (low \<60 beats per minute \[bpm\] and high \>100 bpm). Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits. Data for participants with worst case change from baseline was presented as Baseline to low, Baseline to Normal or No change and Baseline to High.

  Baseline (Day 1) and up to approximately 141 weeks

• Part 2: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Heart Rate

  Heart rate was measured after resting for at least 5 minutes. The abnormal ranges for heart rate were (low \<60 beats per minute \[bpm\] and high \>100 bpm). Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits. Data for participants with worst case change from baseline was presented as Baseline to low, Baseline to Normal or No change and Baseline to High.

  Baseline (Day 1) and up to approximately 212 weeks

• Part 1: Number of Participants With Worst-Case Amount of Increase From Baseline Value in Corrected QT Interval Using Fredericia's Formula (QTcF)

  12-lead electrocardiogram (ECG) was obtained using an automated ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using Fridericia's formula (QTcF) intervals. Grade 0 (\<450 millisecond (msec)), Grade 1 (450-480 msec), Grade 2 (481-500 msec), and Grade 3 (≥501 msec). Higher grade indicates greater severity. Data for participants with worst-case post baseline with any grade increase and a post-baseline grade increase to G2 and G3 from their baseline grade are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 141 weeks

• Part 2: Number of Participants With Worst-Case Amount of Increase From Baseline Value in QTcF

  12-lead electrocardiogram (ECG) was obtained using an automated ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using Fridericia's formula (QTcF) intervals. Grade 0 (\<450 millisecond (msec)), Grade 1 (450-480 msec), Grade 2 (481-500 msec), and Grade 3 (≥501 msec). Higher grade indicates greater severity. Data for participants with worst-case post baseline with any grade increase and a post-baseline grade increase to G2 and G3 from their baseline grade are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 212 weeks

• Part 1: Number of Participants With Worst-case Change Post-baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status

  The number of participants with worst-case post baseline performance status have been presented as 0-5. Where, 0- Fully active; 1- Restricted in strenuous activity but able to carry out light work activities; 2- Capable of self-care but unable to carry out any work activities; 3- Capable of limited self care, confined to bed/chair more than 50% of waking hours; 4- Completely disabled; can't carry on any self care; totally confined to bed/chair and 5- Dead.Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.

  Baseline (Day 1) and up to approximately 141 weeks

• Part 2: Number of Participants With Clinically Significant Abnormalities in ECOG Performance Status

  Any change in ECOG Performance status that was clinically significant in the medical and scientific judgment of the investigator and not related to an underlying disease was reported.

  Baseline (Day 1) and up to approximately 212 weeks

Secondary Outcomes (78)

• Part 1: Area Under the Concentration-time Curve During the Dosing Interval (AUC (0-tau)) Following Single Dose Administration of Belantamab Mafodotin (Antibody-drug Conjugate (ADC))

  Pre-Dose; End of Infusion (EOI); 1 hour (h), 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1

• Part 1: AUC Extrapolated to Infinity (AUC (0-inf)) Following Single Dose Administration of Belantamab Mafodotin (ADC)

  Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1

• Part 1: AUC From Time Zero to the Time of the Last Quantifiable Concentration (AUC (0 - Tlast)) Following Single Dose Administration of Belantamab Mafodotin (ADC)

  Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1

• Part 1: Systemic Clearance (CL) Following Single Dose Administration of Belantamab Mafodotin (ADC)

  Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1

• Part 1: Apparent Terminal Half-life (t1/2) Following Single Dose Administration of Belantamab Mafodotin (ADC)

  Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1

Study Arms (3)

Part 1: Belantamab mafodotin Monotherapy

EXPERIMENTAL

Drug: Belantamab mafodotin

Part 2: Arm A: Belantamab mafodotin+Bortezomib/Dexamethasone

EXPERIMENTAL

Drug: Belantamab mafodotin; Drug: Bortezomib; Drug: Dexamethasone

Part 2: Arm B: Belantamab mafodotin+Pomalidomide/Dexamethasone

EXPERIMENTAL

Drug: Belantamab mafodotin; Drug: Dexamethasone; Drug: Pomalidomide

Interventions

Belantamab mafodotin DRUG

Belantamab mafodotin will be administered as an intravenous infusion.

Part 1: Belantamab mafodotin Monotherapy; Part 2: Arm A: Belantamab mafodotin+Bortezomib/Dexamethasone; Part 2: Arm B: Belantamab mafodotin+Pomalidomide/Dexamethasone

Bortezomib DRUG

Bortezomib solution for injection will be administered subcutaneously.

Part 2: Arm A: Belantamab mafodotin+Bortezomib/Dexamethasone

Dexamethasone DRUG

Dexamethasone tablets will be administered orally.

Part 2: Arm A: Belantamab mafodotin+Bortezomib/Dexamethasone; Part 2: Arm B: Belantamab mafodotin+Pomalidomide/Dexamethasone

Pomalidomide DRUG

Pomalidomide capsules will be administered orally.

Part 2: Arm B: Belantamab mafodotin+Pomalidomide/Dexamethasone

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide signed written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Male or female, 20 years or older (at the time consent is obtained).
• ECOG performance status of 0 to 2.
• Histologically or cytologically confirmed diagnosis of multiple myeloma as defined according to IMWG 2014, criteria in a participant who fulfills all of the following: has undergone stem cell transplant, or is considered transplant ineligible, Part 1: has received at least 2 prior lines of anti-myeloma drugs containing at least 1 proteasome inhibitor and at least 1 immunomodulator, Part 2: has received at least 1 prior line of anti-myeloma drugs; has demonstrated progression on, or within 60 days of completion of the last therapy.
• Has measurable disease with at least one of the following: serum M-protein \>=0.5 grams per deciliter (g/dL) (\>=5 grams per liter \[g/L\]); Urine M-protein \>=200 mg/24 hours; Serum free light chain (FLC) assay: Involved FLC level \>=10 mg/dL (\>=100 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65).
• Participants with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: Transplant was \>100 days prior to study enrolment; No active infection.
• Male participants: 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 6 months after the last dose of GSK2857916, 4 months after the last dose of bortezomib (only Part 2 Arm A), and 4 weeks after the last dose of pomalidomide (only Part 2 Arm B) 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: 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 percent per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females).
• All prior treatment-related toxicities (defined by National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03, must be \<=Grade 1 at the time of enrolment except for alopecia. Participants with Grade 2 peripheral neuropathy can be enrolled into Part 1 and Part 2 Arm B but not into Part 2 Arm A.

You may not qualify if:

• Systemic anti-tumor-therapy within 14 days, or plasmapheresis within 7 days prior to the first dose of study treatment.
• Symptomatic amyloidosis, active 'polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes' (POEMS) syndrome, active plasma cell leukemia at the time of screening.
• Use of an investigational drug within 14 days or 5 half-lives, whichever is shorter, preceding the first dose of study treatment. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study treatment. Prior BCMA targeted therapy.
• History of an allogeneic stem cell transplant.
• Current use of prohibited medications/device or planned use of any of these during the study period.
• Current corneal epithelial disease except mild punctate keratopathy
• Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety). Participants with isolated proteinuria resulting from multiple myeloma are eligible, provided they fulfil the required criteria.
• Evidence of active mucosal or internal bleeding.
• Any major surgery within the last 4 weeks.
• 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.
• Active infection requiring treatment (antibiotic, antiviral, or antifungal treatment).
• Evidence of severe or uncontrolled systemic diseases.
• Malignancies other than disease under study are excluded, except for any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the investigators and Medical Monitor, will not affect the evaluation of the effects of this clinical study treatment on the currently targeted malignancy (multiple myeloma).
• Evidence of cardiovascular risk including any of the following:
• Corrected QT interval Fridericia (QTcF) interval \>=470 milliseconds (msecs) (the QT interval values must be corrected for heart rate by Fridericia's formula \[QTcF\])

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

Shibuya-Ku, Tokyo, 150-8935, Japan

Location

GSK Investigational Site

Aichi, 467-8602, Japan

Location

GSK Investigational Site

Okayama, 701-1192, Japan

Location

GSK Investigational Site

Tokyo, 135-8550, Japan

Location

Related Publications (1)

• Sunami K, Iida S, Tsukada N, Fujii T, Kato H, Fukushima R, Wakabayashi S, Nakano H, Roy-Ghanta S, Kremer BE. DREAMM-11, Part 2: Japanese phase I trial of belantamab mafodotin combination therapies in relapsed/refractory multiple myeloma. Int J Hematol. 2025 Feb;121(2):174-186. doi: 10.1007/s12185-024-03889-8. Epub 2024 Dec 24.

  PMID: 39718747 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

belantamab mafodotin; Bortezomib; Dexamethasone; pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This will be an open-label study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will receive GSK2857916 monotherapy during Part 1 (Dose escalation) of the study on a once every 21 days schedule. During Part 2, participants will receive GSK2857916 given in combination with Bortezomib/Dexamethasone on a once every 21 days schedule (Arm A) or with Pomalidomide/Dexamethasone on a once every 28 days schedule (Arm B).

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: February 4, 2019
• Study Start: March 14, 2019
• Primary Completion: April 6, 2023
• Study Completion: September 5, 2024
• Last Updated: August 19, 2025
• Results First Posted: April 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

JP (4)