Last updated: 08/18/2025 13:30:26
A study to Investigate the efficacy and safety of two doses of GSK2857916 in participants with multiple myeloma who have failed prior treatment with an anti-CD38 antibody
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Phase II, Open Label, Randomized, Two-Arm Study to Investigate the Efficacy and Safety of Two Doses of the Antibody Drug Conjugate GSK2857916 in Participants with Multiple Myeloma Who Had 3 or More Prior Lines of Treatment, Are Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed an Anti-CD38 Antibody (DREAMM 2)
Trial description: Multiple myeloma (MM) is an incurable malignancy and accounts for 1 percentage (%) of all cancers and for 10% of all hematologic malignancies. Participants with relapsed/refractory multiple myeloma (RRMM) will be included in this study, to evaluate the efficacy and safety of belantamab mafodotin (GSK2857916) monotherapy. Participants will be treated with belantamab mafodotin monotherapy until disease progression (PD) or unacceptable toxicity and will be followed for Progression Free Survival and Overall survival. The participants will be randomized to receive either frozen belantamab mafodotin at the dose of 2.5 milligram per kilogram (mg/kg) or 3.4 mg/kg administered Intravenously (IV). There will be an independent cohort of participants who will receive a lyophilized configuration of belantamab mafodotin. For participants who discontinued from the study other than Progressive disease (PD), disease evaluation will continue to be performed at 3-week intervals until confirmed PD, death, start of a new anticancer treatment, withdrawal of consent, or end of the study whichever occurs first.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Overall response rate - Independent Review Committee (IRC)
Timeframe: Every 3 weeks up to 2 years
Secondary outcomes:
Overall response rate - Investigator assessment
Timeframe: Every 3 weeks up to 2 years
Clinical benefit rate (CBR)
Timeframe: Every 3 weeks up to 2 years
Duration of response (DoR)
Timeframe: Every 3 weeks up to 2 years
Time to response
Timeframe: Every 3 weeks up to 2 years
Progression free survival
Timeframe: Every 3 weeks up to 2 years
Time to progression
Timeframe: Every 3 weeks up to 2 years
Overall survival
Timeframe: Every 3 weeks up to 2 years
Number of participants with abnormal hematology parameters
Timeframe: Every 3 weeks up to 2 years
Number of participants with abnormal clinical chemistry parameters
Timeframe: Every 3 weeks up to 2 years
Number of participants with abnormal physical examination parameters
Timeframe: Every 3 weeks up to 2 years
Number of participants with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP) assessment
Timeframe: Every 3 weeks up to 2 years
Number of participants with abnormal pulse rate
Timeframe: Every 3 weeks up to 2 years
Number of participants with abnormal body temperature
Timeframe: Every 3 weeks up to 2 years
Number of participants with adverse events (AEs), serious AEs (SAEs) and AEs of special interest (AESI)
Timeframe: Up to 2 years
Number of participants with abnormal ocular findings
Timeframe: Up to 2 years
Area under the curve (AUC) of belantamab mafodotin
Timeframe: Cycle(C)1 and Cycle3:Day1-Pre-dose, at end of infusion, at 2 and 24 hours after start of infusion; Cycles 1 and 3: Day 4; Day 8 to Day15; Cycles 2,4,6,9 and 12: Pre-dose and at end of infusion; every 6 subsequent cycles at pre-dose (Each cycle of 21days)
Maximum plasma concentration (Cmax) of belantamab mafodotin
Timeframe: Cycle1 and Cycle3:Day1-Pre-dose, at end of infusion, at 2 and 24 hours after start of infusion; Cycles 1 and 3: Day 4; Day 8 to Day15; Cycles 2,4,6,9 and 12: Pre-dose and at end of infusion; every 6 subsequent cycles at pre-dose (Each cycle of 21days)
Time of occurrence of Cmax (Tmax) of belantamab mafodotin
Timeframe: Cycle1 and Cycle3:Day1-Pre-dose, at end of infusion, at 2 and 24 hours after start of infusion; Cycles 1 and 3: Day 4; Day 8 to Day15; Cycles 2,4,6,9 and 12: Pre-dose and at end of infusion; every 6 subsequent cycles at pre-dose (Each cycle of 21days)
Terminal phase half-life (T1/2) of belantamab mafodotin
Timeframe: Cycle1 and Cycle3:Day1-Pre-dose, at end of infusion, at 2 and 24 hours after start of infusion; Cycles 1 and 3: Day 4; Day 8 to Day15; Cycles 2,4,6,9 and 12: Pre-dose and at end of infusion; every 6 subsequent cycles at pre-dose (Each cycle of 21days)
Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin
Timeframe: Cycle 2, Cycle 6, Cycle 9, and Cycle 12: Pre-dose; every 6 subsequent cycles at pre-dose and at EOT (Each cycle of 21 days)
Titers of ADAs against belantamab mafodotin
Timeframe: Cycle 2, Cycle 6, Cycle 9, and Cycle 12: Pre-dose; every 6 subsequent cycles at pre-dose and at EOT (Each cycle of 21 days)
Number of participants with symptomatic AEs measured by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Timeframe: Every 3 weeks up to 2 years
Number of participants with symptomatic AEs measured by National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25)
Timeframe: Every 3 weeks up to 2 years
Number of participants with symptomatic AEs measured by Ocular Surface Disease Index (OSDI)
Timeframe: Every 3 weeks up to 2 years
Change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core module (EORTC QLQ-C30) score
Timeframe: Every 6 weeks up to 2 years
Change in EORTC QLQ- 20-item Multiple Myeloma module (MY-20) score
Timeframe: Every 6 weeks up to 2 years
Interventions:
Drug: Belantamab mafodotin frozen liquid
Drug: Belantamab mafodotin lyophilized powder
Enrollment:
221
Observational study model:
Not applicable
Primary completion date:
2019-21-06
Time perspective:
Not applicable
Clinical publications:
S Lonial, HC Lee, A Badros, S Trudel, AK Nooka, A Chari, A-O Abdallah, N Callander, N Lendvai, D Sborov, A Suvannasankha, K Weisel, L Karlin, E Libby, B Arnulf, T Facon, C Hulin, KM Kortüm, P Rodríguez-Otero, SZ Usmani, P Hari, R Baz, H Quach, P Moreau, PM Voorhees, I Gupta, A Hoos, E Zhi, J Baron, T Piontek, E Lewis, RC Jewell, EJ Dettman, R Popat, S Degli Esposti, J Opalinska, P Richardson, AD Cohen. Single-agent Belantamab Mafodotin for Relapsed or Refractory Multiple Myeloma: Results of the Pivotal Phase II Randomised DREAMM-2 Study. Lancet Oncol. 2020;21(7):207-221 DOI: https://doi.org/10.1016/S1470-2045(19)30788-0 PMID: 31859245
Prawitz T, Popat R, Suvannasankha A, Sarri G, Hughes R, Wang F, Hogea C, Ferrante S, Gorsh B, Willson J, Kapetanakis V.DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs Selinexor + Dexamethasone and Standard of Care in Relapsed/Refractory Multiple Myeloma.Adv Ther.2021; DOI: https://doi.org/10.1007/s12325-021-01884-7 PMID: 34561812
Nooka A, Cohen A, Lee H, Badros A, Suvannasankha A, Callander N, et al. . Single-Agent Belantamab Mafodotin in Patients with Relapsed or Refractory Multiple Myeloma (RRMM): Final Analysis of the DREAMM-2 Trial. Cancer. DOI: 10.1002/cncr.34987 PMID: 37622738
Medical condition
Multiple Myeloma
Product
Not applicable
Collaborators
Not applicable
Study date(s)
June 2018 to September 2024
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Participants who provided signed written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Male or female, 18 years or older.
- Systemic anti-myeloma therapy within <=14 days, or 5 half-lives, whichever is shorter, or plasmapheresis within 7 days prior to the first dose of study drug.
- Systemic treatment with high dose steroids (equivalent to >=60 mg prednisone daily for >=4 days) within the past 14 days if administered to treat MM or non-MM disease.
Inclusion and exclusion criteria
Inclusion criteria:
- Participants who provided signed written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Male or female, 18 years or older.
- Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Participants with histologically or cytologically confirmed diagnosis of MM as defined in IMWG, 2014 criteria, and participant has undergone stem cell transplant or is considered transplant ineligible and has failed at least 3 prior lines of anti-myeloma treatments, including an anti-CD38 antibody (example [e.g.], daratumumab) alone or in combination, and is refractory to an Immunomodulatory drug (IMiD) (that is [i.e.], lenalidomide or pomalidomide), and to a proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib).
- The participant 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 milligram per 24 hours (mg/24h); Serum Free light chain (FLC) assay: Involved FLC level >=10 mg/dL (>=100 mg/Liter) 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 enrollment; no active infection(s); participants meet the remainder of the eligibility criteria outlined in the protocol.
- Participants with adequate organ system functions as defined follows: Absolute neutrophil count (ANC) >=1.0 X 10^9/L; Hemoglobin >=8.0 g/dL; Platelets>= 50 X 10^9/L; Total bilirubin <=1.5X Upper limit of normal (ULN). Isolated bilirubin >=1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent); Alanine aminotransferase (ALT) <=2.5X ULN; Estimated glomerular filtration rate (eGFR) >=30 milliliter per minute per 1.73 meter square (mL/min/m^2); Spot urine (albumin/creatinine ratios [spot urine]) <500 milligram per gram (mg/g) (56 mg per millimoles [mg/mmol]); Left ventricular ejection fraction (LVEF) (Echocardiogram)>=45 percent.
- 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 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 <1% 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; 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 Agree to use a male condom and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as when having sexual intercourse with a WOCBP who is not currently pregnant.
- 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 enrollment except for alopecia and Grade 2 peripheral neuropathy.
- For France only: A participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Exclusion criteria:
- Systemic anti-myeloma therapy within <=14 days, or 5 half-lives, whichever is shorter, or plasmapheresis within 7 days prior to the first dose of study drug.
- Systemic treatment with high dose steroids (equivalent to >=60 mg prednisone daily for >=4 days) within the past 14 days if administered to treat MM or non-MM disease.
- Symptomatic amyloidosis, active ‘polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes’ (POEMS) syndrome, active plasma cell leukemia at the time of screening.
- Prior allogeneic stem cell transplant.
- Current corneal epithelial disease except mild punctate keratopathy.
- Use of an investigational drug within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs. Prior B-cell maturation antigen (BCMA) targeted therapy.
- Evidence of active mucosal or internal bleeding.
- Any major surgery within the last four weeks.
- 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 MM are eligible.
- Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant’s safety, obtaining informed consent or compliance to the study procedures.
- 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.
- 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 principal investigators and GlaxoSmithKline Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy (MM). Participants with curatively treated non-melanoma skin cancer may be enrolled.
- Evidence of cardiovascular risk including any of the following: Corrected QT interval Fridericia (QTcF) interval >480 milliseconds (msec); Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant electrocardiogram 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 six months of Screening; Class III or IV heart failure as defined by the New York Heart Association functional classification system (NYHA); Uncontrolled hypertension.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
- Pregnant or lactating female.
- Active infection requiring antibiotic, antiviral, or antifungal treatment.
- Known Human Immunodeficiency Virus (HIV) infection.
- Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb at screening or within 3 months prior to first dose of study treatment.
- 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.
Trial location(s)
Location
GSK Investigational Site
Indianapolis, IN, United States, 46202
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, PA, United States, 19104
Status
Study Complete
Location
GSK Investigational Site
Salt Lake City, UT, United States, 84112
Status
Study Complete
Location
GSK Investigational Site
Stoke on Trent, United Kingdom, ST4 6QG
Status
Study Complete
Study documents
Study report synopsis
Available language(s): English
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2019-21-06
Actual study completion date
2024-12-09
Plain language summaries
Summary of results in plain language
Available language(s): English, French, German, Italian, Russian, Spanish, Spanish (United States)
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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