Phase 1
N=8
An Open-label, Dose Escalation Study in Japanese Participants With Relapsed/Refractory Multiple Myeloma Who Have Failed Prior Anti Myeloma Treatments
Multiple Myeloma
Bottom Line
View on ClinicalTrials.gov: NCT03828292 ↗Enrolled (actual)
8
Serious AEs
21.1%
Results posted
Apr 2025
Primary outcome: Primary: Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) — 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Belantamab mafodotin (Drug); Bortezomib (Drug); Dexamethasone (Drug); Pomalidomide (Drug)
- Age
- Adult, Older Adult · 20+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Apr 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) |
0; 0 | — |
| PRIMARY Part 2: Arm A: Number of Participants With DLTs |
— | — |
| PRIMARY Part 2: Arm B: Number of Participants With DLTs |
1 | — |
| PRIMARY Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
4; 4; 2; 0 | — |
| PRIMARY Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
3; 4; 0; 1 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Grade Change From Baseline in Clinical Chemistry Parameters |
4; 4; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters |
0; 0; 2; 1; 2; 2 | — |
| PRIMARY Part 2: Number of Participants With Worst-case Grade Change From Baseline in Clinical Chemistry Parameters |
1; 4; 0; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters |
0; 0; 3; 2; 0; 2 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters |
1; 2; 0; 1; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters |
0; 0; 4; 4; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters |
3; 3; 1; 1; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters |
0; 0; 3; 1; 0; 3 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Change in Post Baseline Values Relative to Baseline Urinalysis Results: Occult Blood and Protein |
4; 2; 0; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Worst-case Change in Post Baseline Values Relative to Baseline Urinalysis Results: Occult Blood and Protein |
3; 4; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Change From Baseline (CFB) in Urine Potential of Hydrogen (pH) |
7.13; 5.38; -0.75; 0.67 | — |
| PRIMARY Part 2: Change From Baseline in Urine Potential of Hydrogen (pH) |
6.33; 5.25; 0.00; 1.50 | — |
| PRIMARY Part 1: Change From Baseline in Urine Specific Gravity by Dipstick |
1.0128; 1.0190; -0.0010; -0.0037 | — |
| PRIMARY Part 2: Change From Baseline in Urine Specific Gravity by Dipstick |
1.0167; 1.0218; -0.0070; -0.0055 | — |
| PRIMARY 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) |
3; 2; 2; 1; 1; 0 | — |
| PRIMARY 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) |
2; 2; 2; 1; 0; 1 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Temperature |
0; 0; 4; 4; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Temperature |
0; 0; 3; 4; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Heart Rate |
1; 0; 3; 3; 0; 1 | — |
| PRIMARY Part 2: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Heart Rate |
1; 1; 0; 3; 2; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst-Case Amount of Increase From Baseline Value in Corrected QT Interval Using Fredericia's Formula (QTcF) |
1; 0; 1; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Worst-Case Amount of Increase From Baseline Value in QTcF |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Change Post-baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status |
0; 1; 3; 2; 1; 0 | — |
| PRIMARY Part 2: Number of Participants With Clinically Significant Abnormalities in ECOG Performance Status |
0; 0 | — |
| SECONDARY 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)) |
3694.5965; 3807.9179 | — |
| SECONDARY Part 1: AUC Extrapolated to Infinity (AUC (0-inf)) Following Single Dose Administration of Belantamab Mafodotin (ADC) |
4177.9497; 4243.1678 | — |
| SECONDARY 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) |
3606.0173; 2392.2534 | — |
| SECONDARY Part 1: Systemic Clearance (CL) Following Single Dose Administration of Belantamab Mafodotin (ADC) |
35.026301; 45.340473 | — |
| SECONDARY Part 1: Apparent Terminal Half-life (t1/2) Following Single Dose Administration of Belantamab Mafodotin (ADC) |
7.373; 7.779 | — |
| SECONDARY Part 1: Terminal Phase Rate Constant (Lambda_z) Following Single Dose Administration of Belantamab Mafodotin (ADC) |
0.00385688; 0.00394671 | — |
| SECONDARY Part 1: Volume of Distribution at Steady State (Vss) Following Single Dose Administration of Belantamab Mafodotin (ADC) |
7.475899; 8.216505 | — |
| SECONDARY Part 1: Time of Last Observed Quantifiable Concentration (Tlast) Following Single Dose Administration of Belantamab Mafodotin (ADC) |
21.578; 21.079 | — |
| SECONDARY Part 1: Time to Maximum Plasma Concentration (Tmax) Following Single Dose Administration of Belantamab Mafodotin (ADC) |
2.600; 1.635 | — |
| SECONDARY Part 1: Concentration at the End of Infusion (C-EOI) Following Repeat Dose Administration of Belantamab Mafodotin (ADC) |
30.28; 39.42; 32.52; 31.44; 23.25; 32.20 | — |
| SECONDARY Part 1: Maximum Observed Concentration (Cmax) Following Repeat Dose Administration of Belantamab Mafodotin (ADC) |
36.35; 41.25; 32.52; 31.44; 23.25; 32.20 | — |
| SECONDARY Part 1: Trough Plasma Concentration (Ctrough) Following Repeat Dose Administration of Belantamab Mafodotin (ADC) |
1.45; 1.39; 2.41; 1.76; 3.17; 2.20 | — |
| SECONDARY Part 1: AUC (0-tau) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
6358.4427; 7143.7202 | — |
| SECONDARY Part 1: AUC (0-inf) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
6939.1227; 6789.2291 | — |
| SECONDARY Part 1: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
5839.2501; 4046.1161 | — |
| SECONDARY Part 1: Systemic Clearance (CL) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
22.017014; 25.916718 | — |
| SECONDARY Part 1: t1/2 Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
10.046; 9.512 | — |
| SECONDARY Part 1: Lambda_z Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
0.00319945; 0.00310928 | — |
| SECONDARY Part 1: Vss Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
6.390107; 6.718238 | — |
| SECONDARY Part 1: Tlast Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
18.627; 21.079 | — |
| SECONDARY Part 1: Tmax Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
2.695; 1.675 | — |
| SECONDARY Part 1: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody) |
32.68; 45.65; 38.17; 40.97; 35.56; 46.10 | — |
| SECONDARY Part 1: Cmax Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody) |
39.51; 48.89; 38.17; 40.97; 35.56; 46.10 | — |
| SECONDARY Part 1: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody) |
4.47; 5.19; 6.34; 6.07; 11.40; 4.04 | — |
| SECONDARY Part 1: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin Cysteine Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF) |
73.3412; 141.9031 | — |
| SECONDARY Part 1: Cmax Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
748.94; 2797.27 | — |
| SECONDARY Part 1: Tlast Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
6.940; 6.930 | — |
| SECONDARY Part 1: Tmax Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
16.380; 16.240 | — |
| SECONDARY Part 1: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
304.99; 330.71; 195.09; 221.76; 270.80; 222.00 | — |
| SECONDARY Part 1: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
NA; NA | — |
| SECONDARY Part 1: Observed Accumulation Ratio of C-EOI (R(C-EOI)) Following Repeat Dose Administration of Belantamab Mafodotin (ADC) |
0.783; 0.925 | — |
| SECONDARY Part 1: Observed Accumulation Ratio of Ctrough (R(Ctrough)) Following Repeat Dose Administration of Belantamab Mafodotin (ADC) |
1.561; 1.909 | — |
| SECONDARY Part 1: Observed Accumulation Ratio of C-EOI (R(C-EOI)) Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody) |
1.139; 1.075 | — |
| SECONDARY Part 1: Observed Accumulation Ratio of Ctrough (R(Ctrough)) Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody) |
2.069; 1.775 | — |
| SECONDARY Part 1: Observed Accumulation Ratio of C-EOI (R(C-EOI)) Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
0.603; 0.869 | — |
| SECONDARY Part 2: AUC (0-tau) Following Single Dose Administration of Belantamab Mafodotin (ADC) |
5077.3323; 5489.6508 | — |
| SECONDARY Part 2: AUC (0-inf) Following Single Dose Administration of Belantamab Mafodotin (ADC) |
6201.7657; 6178.4350 | — |
| SECONDARY Part 2: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin (ADC) |
5160.2733; 5166.5353 | — |
| SECONDARY Part 2: CL Following Single Dose Administration of Belantamab Mafodotin (ADC) |
24.684617; 20.900323 | — |
| SECONDARY Part 2: Cmax Following Repeat Dose Administration of Belantamab Mafodotin (ADC) |
47.62; 61.70 | — |
| SECONDARY Part 2: Lambda_z Following Single Dose Administration of Belantamab Mafodotin (ADC) |
0.00302685; 0.00470710 | — |
| SECONDARY Part 2: Vss Following Single Dose Administration of Belantamab Mafodotin (ADC) |
6.801065; 4.537404 | — |
| SECONDARY Part 2: t1/2 Following Single Dose Administration of Belantamab Mafodotin (ADC) |
8.825; 6.195 | — |
| SECONDARY Part 2: Tlast Following Single Dose Administration of Belantamab Mafodotin (ADC) |
21.080; 27.958 | — |
| SECONDARY Part 2: Tmax Following Single Dose Administration of Belantamab Mafodotin (ADC) |
0.780; 1.865 | — |
| SECONDARY Part 2 Arm A: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (ADC) |
46.34; 34.80; 47.20; 35.90; 48.20; 25.60 | — |
| SECONDARY Part 2 Arm A: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (ADC) |
0.56 | — |
| SECONDARY Part 2 Arm B: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (ADC) |
52.96; 34.30; 53.90; 52.10; 45.70; 32.00 | — |
| SECONDARY Part 2 Arm B: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (ADC) |
1.05 | — |
| SECONDARY Part 2: AUC (0-tau) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
9213.7145; 9590.8606 | — |
| SECONDARY Part 2: AUC (0-inf) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
9921.8634 | — |
| SECONDARY Part 2: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
9471.9799; 8495.7663 | — |
| SECONDARY Part 2: Cmax Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody) |
43.51; 52.33 | — |
| SECONDARY Part 2: Lambda_z Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
0.00159877; 0.00305831 | — |
| SECONDARY Part 2: Vss Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
4.367635 | — |
| SECONDARY Part 2: t1/2 Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
16.172; 10.392 | — |
| SECONDARY Part 2: Tlast Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
21.080; 27.958 | — |
| SECONDARY Part 2: Tmax Following Single Dose Administration of Belantamab Mafodotin (Total Antibody) |
1.850; 1.900 | — |
| SECONDARY Part 2: Arm A: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody) |
40.80; 40.80; 38.20; 43.60; 55.70; 30.40 | — |
| SECONDARY Part 2: Arm A: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody) |
2.11; 0.84; 1.77; 1.41; 0.74 | — |
| SECONDARY Part 2: Arm B: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody) |
55.85; 42.40; 46.30; 54.00; 71.40; 34.30 | — |
| SECONDARY Part 2: Arm B: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody) |
4.14; 3.09; 0.82 | — |
| SECONDARY Part 2: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
80.0859; 82.6253 | — |
| SECONDARY Part 2: Cmax Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
857.63; 905.42 | — |
| SECONDARY Part 2: Tlast Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
6.942; 6.865 | — |
| SECONDARY Part 2: Tmax Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
22.370; 22.950 | — |
| SECONDARY Part 2 Arm A: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
319.85; 399.10; 207.50; 88.60; 179.00; 232.00 | — |
| SECONDARY Part 2: Arm A: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
— | — |
| SECONDARY Part 2: Arm B: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
390.28; 428.60; 499.80; 198.00; 269.00; 346.00 | — |
| SECONDARY Part 2: Arm B: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF) |
NA | — |
| SECONDARY Part 1: Number of Participants With Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin |
0; 0 | — |
| SECONDARY Part 2: Number of Participants With Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin |
0; 0 | — |
| SECONDARY Part 1: Titers of ADAs Against Belantamab Mafodotin |
— | — |
| SECONDARY Part 2: Titers of ADAs Against Belantamab Mafodotin |
— | — |
| SECONDARY Part 1 - Percentage of Participants With Overall Response Rate (ORR) |
50; 25 | — |
| SECONDARY Part 2 - Percentage of Participants With ORR |
100; 50 | — |
| SECONDARY Part 1: Clinical Benefit Rate (CBR) |
50; 75 | — |
| SECONDARY Part 2: Clinical Benefit Rate (CBR) |
100; 50 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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 ( 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.
- Female participants: 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 breast feeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) or For Part 1 and Part 2 Arm A: Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of =470 milliseconds (msecs) (the QT interval values must be corrected for heart rate by Fridericia's formula [QTcF])
- Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
- History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 6 months of Screening.
- Class III or IV heart failure as defined by the New York Heart Association functional classification system
- Uncontrolled hypertension
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2857916 or any of the components of the study treatment.
- Pregnant or lactating female or female who are interrupting lactation.
- Known human Immunodeficiency virus (HIV) infection.
- Presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb at Screening or within 3 months prior to first dose of study treatment).
- Positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment. Participants with positive hepatitis C antibody due to prior resolved disease can only be enrolled, if a confirmatory negative hepatitis C RNA test is obtained. Hepatitis RNA testing is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing.
- Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria.
- Previously diagnosed with interstitial lung disease or current complication of interstitial lung disease.
Additional Exclusion Criteria for Part 2 Arm A
- Intolerant to
Data sourced from ClinicalTrials.gov (NCT03828292). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.