Phase 1
N=6
A Study of Belantamab Mafodotin to Investigate Safety, Tolerability, Pharmacokinetics, Immunogenicity and Clinical Activity in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)
Multiple Myeloma
Bottom Line
View on ClinicalTrials.gov: NCT04177823 ↗Enrolled (actual)
6
Serious AEs
16.7%
Results posted
Apr 2024
Primary outcome: Primary: Number of Participants With Adverse Events (AEs) — 6 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Belantamab mafodotin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Dec 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs) |
6 | — |
| PRIMARY Number of Participants With Serious Adverse Events (SAEs) |
1 | — |
| PRIMARY Number of Participants With Dose Limited Toxicities (DLTs) |
1 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC[0-t]) of Belantamab Mafodotin Antibody-drug Conjugate (ADC) |
2819.39 | — |
| SECONDARY AUC[0-t] of Belantamab Mafodotin Total Antibody |
5407.64 | — |
| SECONDARY AUC[0-t] of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF) |
136.17 | — |
| SECONDARY Area Under the Concentration-time Curve During the Dosing Interval (AUC[0-tau]) of Belantamab Mafodotin Antibody-drug Conjugate (ADC) |
2853.73 | — |
| SECONDARY AUC[0-tau] of Belantamab Mafodotin Total Antibody |
4823.61 | — |
| SECONDARY Area Under the Concentration-time Curve From Time 0 to 168h (AUC[0-168]) of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF) |
133.94 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-infinity]) of Belantamab Mafodotin Antibody-drug Conjugate (ADC) |
3000.34 | — |
| SECONDARY AUC[0-infinity] of Belantamab Mafodotin Total Antibody |
5514.32 | — |
| SECONDARY AUC[0-infinity] of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF) |
172.75 | — |
| SECONDARY Observed Plasma Concentration at the End of Infusion (CEOI) of Belantamab Mafodotin Antibody-drug Conjugate (ADC) |
41.50; 36.99; 41.76; 43.69; 40.10; 33.20 | — |
| SECONDARY CEOI of Belantamab Mafodotin Total Antibody |
33.78; 60.36; 58.75; 67.70; 66.00; 64.70 | — |
| SECONDARY CEOI of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF) |
0.53; 0.74; 0.44; 0.47; 0.37; 0.38 | — |
| SECONDARY Maximum Observed Concentration (Cmax) of Belantamab Mafodotin Antibody-drug Conjugate (ADC) |
45.36 | — |
| SECONDARY Cmax of Belantamab Mafodotin Total Antibody |
42.21 | — |
| SECONDARY Cmax of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF) |
1.41 | — |
| SECONDARY Time to Reach Maximum Observed Concentration (Tmax) of Belantamab Mafodotin Antibody-drug Conjugate (ADC) |
2.03 | — |
| SECONDARY Tmax of Belantamab Mafodotin Total Antibody |
2.03 | — |
| SECONDARY Tmax of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF) |
7.96 | — |
| SECONDARY Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) of Belantamab Mafodotin Antibody-drug Conjugate (ADC) |
504.54 | — |
| SECONDARY Tlast of Belantamab Mafodotin Total Antibody |
507.23 | — |
| SECONDARY Tlast of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF) |
168.15 | — |
| SECONDARY Systemic Clearance (CL) of Belantamab Mafodotin Antibody-drug Conjugate (ADC) |
0.0518 | — |
| SECONDARY CL of Belantamab Mafodotin Total Antibody |
0.0300 | — |
| SECONDARY Systemic Clearance Normalized by Body Weight (CL/Weight) of Belantamab Mafodotin Antibody-drug Conjugate (ADC) |
0.83 | — |
| SECONDARY CL/Weight of Belantamab Mafodotin Total Antibody |
0.46 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of Belantamab Mafodotin Antibody-drug Conjugate (ADC) |
7.57 | — |
| SECONDARY Vss of Belantamab Mafodotin Total Antibody |
6.62 | — |
| SECONDARY Volume of Distribution at Steady State Normalized by Body Weight (Vss/Weight) of Belantamab Mafodotin Antibody-drug Conjugate (ADC) |
122.11 | — |
| SECONDARY Vss/Weight of Belantamab Mafodotin Total Antibody |
101.41 | — |
| SECONDARY Apparent Terminal Half-life (t1/2) of Belantamab Mafodotin Antibody-drug Conjugate (ADC) |
128.25 | — |
| SECONDARY t1/2 of Belantamab Mafodotin Total Antibody |
169.20 | — |
| SECONDARY t1/2 of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF) |
73.61 | — |
| SECONDARY Trough Concentration Prior to the Next Dose for Each Cycle (Ctrough) of Belantamab Mafodotin Antibody-drug Conjugate (ADC) |
1.14; 2.43; 5.70; 4.59; 4.41 | — |
| SECONDARY Ctrough of Belantamab Mafodotin Total Antibody |
3.76; 10.25; 24.50; 23.90; 26.40 | — |
| SECONDARY Number of Participants With Abnormal Vital Signs |
— | — |
| SECONDARY Number of Participants With Worst- Case Grade Changes Post-baseline in Hematology Parameter: Hemoglobin, Lymphocytes, Neutrophils, Platelets, Leukocytes |
2; 0; 0; 0; 1; 0 | — |
| SECONDARY Number of Participants With Worst- Case Grade Changes Post-baseline in Clinical Chemistry Parameters |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Objective Response Rate (ORR) |
16.7 | — |
| SECONDARY Number of Participants With Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin |
1 | — |
| SECONDARY Titers of ADAs Against Belantamab Mafodotin |
100 | — |
| SECONDARY Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score |
12.8 | — |
Summary
Multiple myeloma (MM) is a neoplastic plasma cell disorder that is characterized by osteolytic bone lesions, anemia, hypercalcemia and renal failure. belantamab mafodotin was well tolerated in previous studies with at least one dose of belantamab mafodotin in heavily pre-treated participants with relapsed/refractory multiple myeloma (RRMM). This aim of the study is to explore safety, pharmacokinetics (PK), tolerability, immunogenicity and clinical activity of belantamab mafodotin monotherapy in Chinese participants with RRMM who have received at least 2 prior line of anti-myeloma therapy including an alkylator, a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD). This study will include two dose cohorts 2.5 milligram per kilogram (mg/kg) and 3.4 mg/kg. A maximum of 12 participants will be enrolled, 6 each for 2.5 mg/kg cohort and 3.4 mg/kg cohort based on 3+3 design. Participants will be treated until disease progression, intolerable toxicity, end of study or informed consent withdrawal.
Eligibility Criteria
Inclusion Criteria
- Provide signed written informed consent, which includes compliance with requirements and restrictions listed in the consent form.
- Male or female, 18 years or older (at the time consent is obtained).
- Eastern Cooper Oncology Group (ECOG) performance status of 0-2.
- Histological or cytologically confirmed diagnosis of MM as defined according to IMWG criteria and a) Has undergone stem cell transplant or transplant is considered not feasible by local assessment, b) Has failed at least 2 prior lines of anti-myeloma treatments, containing all of the following classes of drugs: alkylating agent, IMID and PI, c) In addition, eligible participant needs to be refractory to an IMiD (i.e.,lenalidomide or pomalidomide), and to a proteasome inhibitor (i.e., bortezomib, ixazomib or carfizomib) as defined by International Myeloma Working Group (IMWG) criteria, d) Participants who failed with cluster of differentiation38 (CD38) antibody (i.e., daratumumab) in previous clinical trials can also be considered to include if they meet the remainder of inclusion criteria in this protocol.
- Has measurable disease with at least one of the following: a) Serum M-protein greater than or equal to 0.5 grams per deciliter (g/dL) (5 g/L) , b) Urine M-protein greater than or equal to 200 mg/24hour, c) Serum Free light chain (FLC) assay: Involved FLC level greater than or equal to10 mg/dL (greater than or equal to 100 mg/L) and an abnormal serum free light chain ratio (less than 0.26 or greater than 1.65)
- Participants with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: a) Transplant was greater than 100 days prior to study enrolment, b) No active infection(s), c) Participant meets the remainder of the eligibility criteria outlined in this protocol.
- Adequate organ system functions.
- Female Participants: Contraceptive use by men or 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 one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) or is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of less than 1 percent per year), preferably with low user dependency, during the intervention period and for at least 80 days after the last dose of study intervention 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 intervention. 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 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.
- Male Participants: Contraceptive use by men or women 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 during the intervention period and for at least 140 days: 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 and female partner to use an additional highly effective contraceptive method with a failure rate of less than 1 percent per year as when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
- All prior treatment-related tox
Data sourced from ClinicalTrials.gov (NCT04177823). 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.