Clinical trial NCT03828292: An Open-label, Dose Escalation Study in Japanese Participants With Relapsed/Refractory Multiple Myeloma Who Have Failed Prior Anti Myeloma Treatments
Official title: A Phase I Open-Label, Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of the Antibody Drug Conjugate GSK2857916 in Japanese Participants With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Antibody drug conjugate
Dose-escalation
GSK2857916
Japanese
Relapsed/Refractory Multiple Myeloma
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2019-02-04
Enrollment: 15
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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).
Primary purpose: TREATMENT

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.


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 (\<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.
* 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 \<1 percent per year), preferably with low user dependency, during the treatment period and for 4 months after the last dose of GSK2857916, and 7 months from the last dose of bortezomib (only Part 2 Arm A), and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment. A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study treatment and agree to use effective contraception during the study and for 4 months after the last dose of GSK2857916, and 7 months from the last dose of bortezomib (only Part 2 Arm A); For Part 2 Arm B: Due to pomalidomide being a thalidomide analogue with risk for embryo-fetal toxicity and prescribed under a restricted distribution program, WOCBP participants will be eligible if they commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of pomalidomide treatment. Thereafter, WOCBP participants must use a contraceptive method that is highly effective (with a failure rate of \<1 percent per year) for a further 3 months, and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. Two negative pregnancy tests must be obtained prior to initiating pomalidomide therapy. The first test should be performed within 10 to 14 days and the second test within 24 hours prior to prescribing pomalidomide therapy. 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.
* 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.
* Adequate Organ System Function. Exclusion Criteria
* 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:

  1. Corrected QT interval Fridericia (QTcF) interval \>=470 milliseconds (msecs) (the QT interval values must be corrected for heart rate by Fridericia's formula \[QTcF\])
  2. Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
  3. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 6 months of Screening.
  4. Class III or IV heart failure as defined by the New York Heart Association functional classification system
  5. 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 bortezomib or refractory to bortezomib.
* Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain.
* Intolerance or contraindications to herpes zoster prophylaxis Additional Exclusion Criteria for Part 2 Arm B
* Prior pomalidomide use.
* Intolerance or contraindications to antithrombotic prophylaxis.
* Active or history of venous thromboembolism within 3 months prior to first dose of study treatment.

Primary outcomes:
measure: Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Up to Day 21
measure: Part 2: Arm A: Number of Participants With DLTs
timeFrame: Up to Day 21
measure: Part 2: Arm B: Number of Participants With DLTs
timeFrame: Up to Day 28
measure: Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 141 weeks
measure: Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 212 weeks
measure: Part 1: Number of Participants With Worst-case Grade Change From Baseline in Clinical Chemistry Parameters
timeFrame: Baseline (Day 1) and up to approximately 141 weeks
measure: Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters
timeFrame: Baseline (Day 1) and up to approximately 141 weeks
measure: Part 2: Number of Participants With Worst-case Grade Change From Baseline in Clinical Chemistry Parameters
timeFrame: Baseline (Day 1) and up to approximately 212 weeks
measure: Part 2: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters
timeFrame: Baseline (Day 1) and up to approximately 212 weeks
measure: Part 1: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters
timeFrame: Baseline (Day 1) and up to approximately 141 weeks
measure: Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters
timeFrame: Baseline (Day 1) and up to approximately 141 weeks
measure: Part 2: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters
timeFrame: Baseline (Day 1) and up to approximately 212 weeks
measure: Part 2: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters
timeFrame: Baseline (Day 1) and up to approximately 212 weeks
measure: Part 1: Number of Participants With Worst-case Change in Post Baseline Values Relative to Baseline Urinalysis Results: Occult Blood and Protein
timeFrame: Baseline (Day 1) and up to approximately 141 weeks
measure: Part 2: Number of Participants With Worst-case Change in Post Baseline Values Relative to Baseline Urinalysis Results: Occult Blood and Protein
timeFrame: Baseline (Day 1) and up to approximately 212 weeks
measure: Part 1: Change From Baseline (CFB) in Urine Potential of Hydrogen (pH)
timeFrame: Baseline (Day 1) and up to approximately 141 weeks
measure: Part 2: Change From Baseline in Urine Potential of Hydrogen (pH)
timeFrame: Baseline (Day 1) and up to approximately 212 weeks
measure: Part 1: Change From Baseline in Urine Specific Gravity by Dipstick
timeFrame: Baseline (Day 1) and up to approximately 141 weeks
measure: Part 2: Change From Baseline in Urine Specific Gravity by Dipstick
timeFrame: Baseline (Day 1) and up to approximately 212 weeks
measure: 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)
timeFrame: Baseline (Day 1) and up to approximately 141 weeks
measure: 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)
timeFrame: Baseline (Day 1) and up to approximately 212 weeks
measure: Part 1: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Temperature
timeFrame: Baseline (Day 1) and up to approximately 141 weeks
measure: Part 2: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Temperature
timeFrame: Baseline (Day 1) and up to approximately 212 weeks
measure: Part 1: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Heart Rate
timeFrame: Baseline (Day 1) and up to approximately 141 weeks
measure: Part 2: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Heart Rate
timeFrame: Baseline (Day 1) and up to approximately 212 weeks
measure: Part 1: Number of Participants With Worst-Case Amount of Increase From Baseline Value in Corrected QT Interval Using Fredericia's Formula (QTcF)
timeFrame: Baseline (Day 1) and up to approximately 141 weeks
measure: Part 2: Number of Participants With Worst-Case Amount of Increase From Baseline Value in QTcF
timeFrame: Baseline (Day 1) and up to approximately 212 weeks
measure: Part 1: Number of Participants With Worst-case Change Post-baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: Baseline (Day 1) and up to approximately 141 weeks
measure: Part 2: Number of Participants With Clinically Significant Abnormalities in ECOG Performance Status
timeFrame: Baseline (Day 1) and up to approximately 212 weeks
Secondary outcomes:
measure: 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))
timeFrame: 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
measure: Part 1: AUC Extrapolated to Infinity (AUC (0-inf)) Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: Part 1: Systemic Clearance (CL) Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: 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
measure: Part 1: Apparent Terminal Half-life (t1/2) Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: 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
measure: Part 1: Terminal Phase Rate Constant (Lambda_z) Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: 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
measure: Part 1: Volume of Distribution at Steady State (Vss) Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: 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
measure: Part 1: Time of Last Observed Quantifiable Concentration (Tlast) Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: 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
measure: Part 1: Time to Maximum Plasma Concentration (Tmax) Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: 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
measure: Part 1: Concentration at the End of Infusion (C-EOI) Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
measure: Part 1: Maximum Observed Concentration (Cmax) Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
measure: Part 1: Trough Plasma Concentration (Ctrough) Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Cycle 1, Cycle 2, Cycle 5, Cycle 8 and Cycle 11
measure: Part 1: AUC (0-tau) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: 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
measure: Part 1: AUC (0-inf) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: 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
measure: Part 1: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: 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
measure: Part 1: Systemic Clearance (CL) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: 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
measure: Part 1: t1/2 Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: 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
measure: Part 1: Lambda_z Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: 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
measure: Part 1: Vss Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: 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
measure: Part 1: Tlast Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: 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
measure: Part 1: Tmax Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: 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
measure: Part 1: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
measure: Part 1: Cmax Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
measure: Part 1: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Cycle 1, Cycle 2, Cycle 5, Cycle 8 and Cycle 11
measure: Part 1: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin Cysteine Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF)
timeFrame: 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
measure: Part 1: Cmax Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: 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
measure: Part 1: Tlast Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: 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
measure: Part 1: Tmax Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: 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
measure: Part 1: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
measure: Part 1: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: Cycle 1, Cycle 2, Cycle 5, Cycle 8 and Cycle 11
measure: Part 1: Observed Accumulation Ratio of C-EOI (R(C-EOI)) Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
measure: Part 1: Observed Accumulation Ratio of Ctrough (R(Ctrough)) Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Cycle 1, Cycle 2, Cycle 5, Cycle 8 and Cycle 11
measure: Part 1: Observed Accumulation Ratio of C-EOI (R(C-EOI)) Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
measure: Part 1: Observed Accumulation Ratio of Ctrough (R(Ctrough)) Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Cycle 1, Cycle 2, Cycle 5, Cycle 8 and Cycle 11
measure: Part 1: Observed Accumulation Ratio of C-EOI (R(C-EOI)) Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
measure: Part 2: AUC (0-tau) Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: AUC (0-inf) Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: CL Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Cmax Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Lambda_z Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Vss Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: t1/2 Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Tlast Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Tmax Following Single Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2 Arm A: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Cycle 1, Cycle 4, Cycle 6, Cycle 9, Cycle 10, Cycle 11 and Cycle 12
measure: Part 2 Arm A: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Cycle 3, Cycle 5, Cycle 8, Cycle 9, Cycle 10 and Cycle 11
measure: Part 2 Arm B: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Cycle 1, Cycle 2, Cycle 4, Cycle 10, Cycle 11 and Cycle 24
measure: Part 2 Arm B: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
timeFrame: Cycle 1, Cycle 3, Cycle 9, Cycle 10 and Cycle 23
measure: Part 2: AUC (0-tau) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: AUC (0-inf) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Cmax Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Lambda_z Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Vss Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: t1/2 Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Tlast Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Tmax Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Arm A: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Cycle 1, Cycle 4, Cycle 6, Cycle 9, Cycle 10, Cycle 11 and Cycle 12
measure: Part 2: Arm A: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Cycle 3, Cycle 5, Cycle 8, Cycle 9, Cycle 10 and Cycle 11
measure: Part 2: Arm B: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Cycle 1, Cycle 2, Cycle 4, Cycle 10, Cycle 11 and Cycle 24
measure: Part 2: Arm B: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
timeFrame: Cycle 1, Cycle 3, Cycle 9, Cycle 10 and Cycle 23
measure: Part 2: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Cmax Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Tlast Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2: Tmax Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
measure: Part 2 Arm A: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: Cycle 1, Cycle 4, Cycle 6, Cycle 9, Cycle 10, Cycle 11 and Cycle 12
measure: Part 2: Arm A: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: Cycle 3, Cycle 5, Cycle 8, Cycle 9, Cycle 10 and Cycle 11
measure: Part 2: Arm B: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: Cycle 1, Cycle 2, Cycle 4, Cycle 10, Cycle 11 and Cycle 24
measure: Part 2: Arm B: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
timeFrame: Cycle 1, Cycle 3, Cycle 9, Cycle 10 and Cycle 23
measure: Part 1: Number of Participants With Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin
timeFrame: Up to approximately 141 weeks
measure: Part 2: Number of Participants With Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin
timeFrame: Up to approximately 212 weeks
measure: Part 1: Titers of ADAs Against Belantamab Mafodotin
timeFrame: Up to approximately 141 weeks
measure: Part 2: Titers of ADAs Against Belantamab Mafodotin
timeFrame: Up to approximately 212 weeks
measure: Part 1 - Percentage of Participants With Overall Response Rate (ORR)
timeFrame: Up to approximately 141 weeks
measure: Part 2 - Percentage of Participants With ORR
timeFrame: Up to approximately 212 weeks
measure: Part 1: Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 141 weeks
measure: Part 2: Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 212 weeks
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.