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

NCT03525678 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2056782017-004810-25
• Study Type: interventional
• Target: 221
• Locations: 8 countries
• Sites: 59

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

Relapsed Refractory multiple myeloma; Antibody-drug conjugate; Patient-Reported Outcome Version of the Common Term Criteria for Adverse Events; Quality of Life Questionnaire 20-item Multiple Myeloma module; Multiple Myeloma; Quality of Life Questionnaire 30-item Core module

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR) by Independent Review Committee (IRC) (Full Analysis Population)

  ORR was determined according to the 2016 international myeloma working group (IMWG) response criteria by IRC. ORR was calculated as the percentage of participants with a confirmed partial response (PR) or better (that is \[i.e.\], PR, very good partial response \[VGPR\], complete response \[CR\] and stringent complete response \[sCR\]). Confidence intervals were based on the exact method.

  Up to 48 weeks

• Overall Response Rate by Independent Review Committee (Efficacy Population)

  ORR was determined according to the 2016 IMWG response criteria by IRC. ORR was calculated as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR and sCR). Confidence intervals were based on the exact method. Efficacy Population comprised of first 130 intent-to-treat participants whether or not randomized treatment (frozen solution) was administered. Intent-to-treat Population comprised of all randomized participants whether or not randomized treatment was administered.

  Up to 48 weeks

Secondary Outcomes (60)

• Overall Response Rate by Investigator Assessment (IA) (Full Analysis Population)

  Up to 186 weeks

• Overall Response Rate by Investigator Assessment (Efficacy Population)

  Up to 186 weeks

• Clinical Benefit Rate (CBR) by Investigator Assessment (Full Analysis Population)

  Up to 186 weeks

• Clinical Benefit Rate by Investigator Assessment (Efficacy Population)

  Up to 186 weeks

• Clinical Benefit Rate by Independent Review Committee (Full Analysis Population)

  Up to 186 weeks

Study Arms (3)

Participants receiving frozen 2.5 mg/kg belantamab mafodotin

EXPERIMENTAL

Participants will receive 2.5 mg/kg frozen liquid belantamab mafodotin. Participants will be administered with frozen liquid belantamab mafodotin via infusion pump every 3 weeks.

Drug: Belantamab mafodotin frozen liquid

Participants receiving frozen 3.4 mg/kg belantamab mafodotin

EXPERIMENTAL

Participants will receive 3.4 mg/kg frozen liquid belantamab mafodotin. Participants will be administered with frozen liquid belantamab mafodotin via infusion pump every 3 weeks.

Drug: Belantamab mafodotin frozen liquid

Participants receiving lyophilized belantamab mafodotin

EXPERIMENTAL

Participants in lyophilized arm will receive lyophilized belantamab mafodotin once lyophilized configuration becomes available and enrollment has been completed for frozen liquid arms.

Drug: Belantamab mafodotin lyophilized powder

Interventions

Belantamab mafodotin frozen liquid DRUG

Belantamab mafodotin will be available as frozen liquid. Frozen liquid will be available as 30 milligram (mg)/vial solution in a single use vial with unit dose strength of 2.5 or 3.4 mg/kg. Belantamab mafodotin will be administered as IV solution over at least 30 minutes. Frozen belantamab mafodotin will be diluted in 0.9 percent saline and administered via infusion pump.

Participants receiving frozen 2.5 mg/kg belantamab mafodotin; Participants receiving frozen 3.4 mg/kg belantamab mafodotin

Belantamab mafodotin lyophilized powder DRUG

Belantamab mafodotin will be available as lyophilized powder. Lyophilized powder will be available as 100 mg/vial in single-use vial for reconstitution with unit dose strength of 3.4 mg/kg. Lyophilized belantamab mafodotin will be reconstituted using water for injection and diluted with saline before use.

Participants receiving lyophilized belantamab mafodotin

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (59)

GSK Investigational Site

New Haven, Connecticut, 06510, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30322, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30342, United States

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GSK Investigational Site

Chicago, Illinois, 60612, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

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GSK Investigational Site

Indianapolis, Indiana, 46202, United States

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GSK Investigational Site

Fairway, Kansas, 66205, United States

Location

GSK Investigational Site

Baton Rouge, Louisiana, 70121, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21201, United States

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GSK Investigational Site

Boston, Massachusetts, 02215, United States

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GSK Investigational Site

Rochester, Minnesota, 55905, United States

Location

GSK Investigational Site

New York, New York, 10029, United States

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GSK Investigational Site

New York, New York, 10065, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28204, United States

Location

GSK Investigational Site

Columbus, Ohio, 43210, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37232, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Salt Lake City, Utah, 84112, United States

Location

GSK Investigational Site

Seattle, Washington, 98109, United States

Location

GSK Investigational Site

Madison, Wisconsin, 53792, United States

Location

GSK Investigational Site

Woodville, South Australia, 5011, Australia

Location

GSK Investigational Site

Fitzroy, Victoria, 3065, Australia

Location

GSK Investigational Site

Melbourne, Victoria, 3004, Australia

Location

GSK Investigational Site

Calgary, Alberta, T2N 4N2, Canada

Location

GSK Investigational Site

Winnipeg, Manitoba, R3E 0V9, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

GSK Investigational Site

Lille, 59037, France

Location

GSK Investigational Site

Nantes, 44093, France

Location

GSK Investigational Site

Paris, 75010, France

Location

GSK Investigational Site

Pessac, 33600, France

Location

GSK Investigational Site

Pierre-Bénite, 69495, France

Location

GSK Investigational Site

Toulouse, 31059, France

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GSK Investigational Site

Dresden, 01307, Germany

Location

GSK Investigational Site

Hanover, 30625, Germany

Location

GSK Investigational Site

Koblenz, 56068, Germany

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GSK Investigational Site

Schwerin, 19049, Germany

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GSK Investigational Site

Tübingen, 72076, Germany

Location

GSK Investigational Site

Würzburg, 97080, Germany

Location

GSK Investigational Site

Aviano PN, 33081, Italy

Location

GSK Investigational Site

Parma, 43126, Italy

Location

GSK Investigational Site

Rionero in Vulture PZ, 85028, Italy

Location

GSK Investigational Site

Torino, 10126, Italy

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Granada, 18014, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28223, Spain

Location

GSK Investigational Site

Murcia, 30008, Spain

Location

GSK Investigational Site

PamplonaNavarra, 31008, Spain

Location

GSK Investigational Site

Salamanca, 37007, Spain

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GSK Investigational Site

Valencia, 46017, Spain

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GSK Investigational Site

Birmingham, B9 5SS, United Kingdom

Location

GSK Investigational Site

Bournemouth, BH7 7DW, United Kingdom

Location

GSK Investigational Site

London, NW1 2BU, United Kingdom

Location

GSK Investigational Site

Nottingham, NG5 1PB, United Kingdom

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GSK Investigational Site

Oxford, OX3 7LE, United Kingdom

Location

GSK Investigational Site

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

GSK Investigational Site

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (8)

• Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, Abdallah AO, Callander N, Lendvai N, Sborov D, Suvannasankha A, Weisel K, Karlin L, Libby E, Arnulf B, Facon T, Hulin C, Kortum KM, Rodriguez-Otero P, Usmani SZ, Hari P, Baz R, Quach H, Moreau P, Voorhees PM, Gupta I, Hoos A, Zhi E, Baron J, Piontek T, Lewis E, Jewell RC, Dettman EJ, Popat R, Esposti SD, Opalinska J, Richardson P, Cohen AD. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020 Feb;21(2):207-221. doi: 10.1016/S1470-2045(19)30788-0. Epub 2019 Dec 16.

  PMID: 31859245 BACKGROUND

• Prawitz T, Popat R, Suvannasankha A, Sarri G, Hughes R, Wang F, Hogea C, Ferrante SA, Gorsh B, Willson J, Kapetanakis V. DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma. Adv Ther. 2021 Nov;38(11):5501-5518. doi: 10.1007/s12325-021-01884-7. Epub 2021 Sep 24.

  PMID: 34561812 BACKGROUND

• Nooka AK, Cohen AD, Lee HC, Badros A, Suvannasankha A, Callander N, Abdallah AO, Trudel S, Chari A, Libby EN, Chaudhry M, Hultcrantz M, Kortum KM, Popat R, Sborov D, Hakim S, Lewis E, Gorsh B, Bhushan B, McKeown A, Gupta I, Opalinska J, Richardson PG, Lonial S. Single-agent belantamab mafodotin in patients with relapsed/refractory multiple myeloma: Final analysis of the DREAMM-2 trial. Cancer. 2023 Dec 1;129(23):3746-3760. doi: 10.1002/cncr.34987. Epub 2023 Aug 25.

  PMID: 37622738 BACKGROUND

• Collins J, van Noort M, Rathi C, Post TM, Struemper H, Jewell RC, Ferron-Brady G. Longitudinal efficacy and safety modeling and simulation framework to aid dose selection of belantamab mafodotin for patients with multiple myeloma. CPT Pharmacometrics Syst Pharmacol. 2023 Oct;12(10):1411-1424. doi: 10.1002/psp4.13016. Epub 2023 Aug 2.

  PMID: 37465991 DERIVED

• Nikolaou A, Ambavane A, Shah A, Ma W, Tosh J, Kapetanakis V, Willson J, Wang F, Hogea C, Gorsh B, Gutierrez B, Sapra S, Suvannasankha A, Samyshkin Y. Belantamab mafodotin for the treatment of relapsed/refractory multiple myeloma in heavily pretreated patients: a US cost-effectiveness analysis. Expert Rev Hematol. 2021 Dec;14(12):1137-1145. doi: 10.1080/17474086.2021.1970522. Epub 2021 Sep 20.

  PMID: 34465265 DERIVED

• Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, Abdallah AO, Callander N, Sborov D, Suvannasankha A, Weisel K, Voorhees PM, Womersley L, Baron J, Piontek T, Lewis E, Opalinska J, Gupta I, Cohen AD. Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. Cancer. 2021 Nov 15;127(22):4198-4212. doi: 10.1002/cncr.33809. Epub 2021 Jul 27.

  PMID: 34314018 DERIVED

• Lonial S, Nooka AK, Thulasi P, Badros AZ, Jeng BH, Callander NS, Potter HA, Sborov D, Zaugg BE, Popat R, Degli Esposti S, Byrne J, Opalinska J, Baron J, Piontek T, Gupta I, Dana R, Farooq AV, Colby K, Jakubowiak A. Management of belantamab mafodotin-associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM). Blood Cancer J. 2021 May 26;11(5):103. doi: 10.1038/s41408-021-00494-4.

  PMID: 34039952 DERIVED

• Farooq AV, Degli Esposti S, Popat R, Thulasi P, Lonial S, Nooka AK, Jakubowiak A, Sborov D, Zaugg BE, Badros AZ, Jeng BH, Callander NS, Opalinska J, Baron J, Piontek T, Byrne J, Gupta I, Colby K. Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. Ophthalmol Ther. 2020 Dec;9(4):889-911. doi: 10.1007/s40123-020-00280-8. Epub 2020 Jul 25.

  PMID: 32712806 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

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

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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2018
• First Posted: May 16, 2018
• Study Start: June 18, 2018
• Primary Completion: June 21, 2019
• Study Completion: September 12, 2024
• Last Updated: September 3, 2025
• Results First Posted: April 28, 2020

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (21); IT (4); ES (9); CA (3); FR (6); GB (7); DE (6); AU (3)