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Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM 5)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04126200
Recruitment Status : Recruiting
First Posted : October 15, 2019
Last Update Posted : September 28, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE October 11, 2019
First Posted Date  ICMJE October 15, 2019
Last Update Posted Date September 28, 2020
Actual Study Start Date  ICMJE October 7, 2019
Estimated Primary Completion Date February 24, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 6, 2020)
  • DE Phase: Number of participants achieving dose limiting toxicities (DLT) [ Time Frame: Up to 36 months ]
    An event is considered to be a dose DLT if the event occurs within the first 21 days of treatment and meets the dose limiting toxicity criteria.
  • DE Phase: Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 36 months ]
    AEs and SAEs will be collected.
  • DE Phase: Number of participants with abnormality in vital signs [ Time Frame: Up to 36 months ]
    Vital sign measurements will include systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate.
  • DE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters [ Time Frame: Up to 36 months ]
    Blood and urine samples will be collected to evaluate hematology, clinical chemistry and urinalysis lab parameters.
  • CE Phase: Number of participants achieving Overall Response Rate (ORR) [ Time Frame: Up to 36 months ]
    ORR is defined as the percentage of participants with a Partial response (PR) or better, according to the International Myeloma Working Group (IMWG) Response Criteria.
Original Primary Outcome Measures  ICMJE
 (submitted: October 11, 2019)
  • DE Phase: Number of participants achieving dose limiting toxicities (DLT) [ Time Frame: Up to 36 months ]
    An event is considered to be a dose DLT if the event occurs within the first 21 days of treatment and meets the dose limiting toxicity criteria.
  • DE Phase: Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 36 months ]
    An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A serious adverse event is defined as any untoward medical occurrence that, at any dose; results in death or is life-threatening, or requires inpatient hospitalization or prolongation of existing hospitalization, or results in persistent disability/incapacity, or is a congenital anomaly/birth defect, or other situations where medical or scientific judgment should be exercised in deciding whether SAE reporting is appropriate such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.
  • DE Phase: Number of participants with abnormality in vital signs [ Time Frame: Up to 36 months ]
    Vital sign measurements will include systolic and diastolic blood pressure, temperature, and pulse rate.
  • DE Phase: Number of participants with abnormality in hematology parameters [ Time Frame: Up to 36 months ]
    Blood samples will be collected to evaluate platelet count, red blood cell (RBC) count, white blood cell (WBC) count (absolute), reticulocyte count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), neutrophils, lymphocytes, monocytes, eosinophils and basophils.
  • DE Phase: Number of participants with abnormality in clinical chemistry parameters [ Time Frame: Up to 36 months ]
    Blood samples will be collected to evaluate urea nitrogen, creatinine, glucose, sodium, magnesium, potassium, chloride, total carbon dioxide/ bicarbonate, calcium (uncorrected), phosphorous, calcium corrected for albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, creatine kinase (CK), total and direct bilirubin, uric acid, albumin, total Protein and lactate dehydrogenase (LDH).
  • DE Phase: Number of participants with abnormality in routine urinalysis parameters [ Time Frame: Up to 36 months ]
    Urinalysis parameters will be analyzed including specific gravity, pH, glucose, protein, blood, ketones and spot urine (albumin/creatinine ratio). Microscopic examination will be performed if blood or protein is abnormal.
  • CE Phase: Number of participants achieving Overall Response Rate (ORR) [ Time Frame: Up to 36 months ]
    ORR is defined as the percentage of participants with a Partial response (PR) or better, according to the International Myeloma Working Group (IMWG) Response Criteria.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2020)
  • DE Phase: Number of participants achieving ORR [ Time Frame: Up to 36 months ]
    ORR is defined as the percentage of participants with PR or better, according to the IMWG Response Criteria.
  • CE Phase: Number of participants achieving Clinical Benefit Rate (CBR) [ Time Frame: Up to 36 months ]
    CBR is defined as the percentage of participants with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents.
  • DE Phase and CE Phase: Number of participants achieving Partial Response [ Time Frame: Up to 36 months ]
    Number of participants with PR according to IMWG criteria will be analyzed.
  • DE Phase and CE Phase: Number of participants achieving Very Good Partial Response (VGPR) [ Time Frame: Up to 36 months ]
    Number of participants with VGPR according to IMWG criteria will be analyzed.
  • DE Phase and CE Phase: Number of participants achieving Complete Response (CR) [ Time Frame: Up to 36 months ]
    Participants with CR according to IMWG criteria will be analyzed.
  • DE Phase and CE Phase: Number of participants achieving stringent Complete Response (sCR) [ Time Frame: Up to 36 months ]
    Participants with sCR according to IMWG criteria will be analyzed.
  • DE Phase and CE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments [ Time Frame: Up to 36 months ]
    Blood samples will be collected for concentrations of belantamab mafodotin.
  • DE Phase and CE Phase: GSK3174998 concentration when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples will be collected for concentrations of GSK3174998.
  • DE Phase and CE Phase: GSK3359609 concentration when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples will be collected for concentrations of GSK3359609.
  • DE Phase and CE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples will be collected for concentrations of nirogacestat.
  • DE Phase and CE Phase: Dostarlimab concentration when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples will be collected for concentrations of dostarlimab.
  • DE Phase and CE Phase: Concentration of anti-drug antibodies (ADAs) against belantamab mafodotin when administered in combination with anti-cancer treatments [ Time Frame: Up to 36 months ]
    Blood samples for concentrations for ADAs will be collected.
  • DE Phase and CE Phase: Concentration of ADAs against GSK3174998 when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples for concentrations for ADAs will be collected.
  • DE Phase and CE Phase: Concentration of ADAs against GSK3359609 when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples for concentrations for ADAs will be collected.
  • DE Phase and CE Phase: Concentration of ADAs against dostarlimab when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples for concentrations for ADAs will be collected.
  • DE Phase and CE Phase: Number of participants with adverse events of special interest (AESI) [ Time Frame: Up to 36 months ]
    AESIs will be collected.
  • DE Phase and CE Phase: Number of participants with abnormal ocular findings on ophthalmic examination [ Time Frame: Up to 36 months ]
    Ophthalmic examination will assess abnormal findings.
  • CE Phase: Number of participants achieving Progression-free survival (PFS) [ Time Frame: Up to 36 months ]
    PFS is defined as the time from randomization until the earliest date of confirmed progressive disease (PD) per IMWG, or death due to any cause.
  • CE Phase: Duration of response (DoR) [ Time Frame: Up to 36 months ]
    DoR is defined as the time from first documented evidence or PR or better until progressive disease per IMWG or death due to progressive disease among participants who achieve confirmed partial response or better.
  • CE Phase: Time to response (TTR) [ Time Frame: Up to 36 months ]
    TTR is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (confirmed PR or better).
  • CE Phase: Number of participants achieving Overall survival (OS) [ Time Frame: Up to 36 months ]
    OS is defined as the time from randomization until death due to any cause.
  • CE Phase: Number of participants with AEs and SAEs [ Time Frame: Up to 36 months ]
    AEs and SAEs will be collected.
  • CE Phase: Number of participants with AEs leading to discontinuation [ Time Frame: Up to 36 months ]
    Number of participants with AEs leading to discontinuation will be evaluated.
  • CE Phase: Number of participants with dose reduction or delay [ Time Frame: Up to 36 months ]
    Number of participants with dose reduction or delay will be evaluated.
  • CE Phase: Number of participants with abnormality in vital signs [ Time Frame: Up to 36 months ]
    Vital sign measurements will include systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate.
  • CE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters [ Time Frame: Up to 36 months ]
    Blood and urine samples will be collected to evaluate hematology, clinical chemistry and urinalysis lab parameters.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2019)
  • DE Phase: Number of participants achieving ORR [ Time Frame: Up to 36 months ]
    ORR is defined as the percentage of participants with PR or better, according to the IMWG Response Criteria.
  • DE Phase: Concentration observed of GSK'916 (belantamab mafodotin) when administered in combination with GSK3174998 [ Time Frame: Up to 36 months ]
    The exposure of GSK'916 (belantamab mafodotin) when administered in combination with GSK3174998 in participants with RRMM will be evaluated. The concentration of GSK'916 (belantamab mafodotin) will be analyzed using a population pharmacokinetic approach.
  • DE Phase: Concentration observed of GSK'916 (belantamab mafodotin) when administered in combination with GSK3359609 [ Time Frame: Up to 36 months ]
    The exposure of GSK'916 (belantamab mafodotin) when administered in combination GSK3359609 in participants with RRMM will be evaluated. The concentration of GSK'916 (belantamab mafodotin) will be analyzed using a population pharmacokinetic approach.
  • DE Phase: Concentration observed of GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) [ Time Frame: Up to 36 months ]
    The exposure of GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) in participants with RRMM will be evaluated. The concentration of GSK3174998 will be analyzed using a population pharmacokinetic approach.
  • DE Phase: Concentration observed of GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) [ Time Frame: Up to 36 months ]
    The exposure of GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) in participants with RRMM will be evaluated. The concentration of GSK3359609 will be analyzed using a population pharmacokinetic approach.
  • DE Phase: Concentration of anti-drug antibodies (ADAs) against GSK'916 (belantamab mafodotin) when administered in combination with GSK3174998 [ Time Frame: Up to 36 months ]
    Concentration of ADAs against GSK'916 (belantamab mafodotin) after administration of GSK'916 (belantamab mafodotin) in combination with GSK3174998 will be evaluated.
  • DE Phase: Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with GSK3359609 [ Time Frame: Up to 36 months ]
    Concentration of ADAs against GSK'916 (belantamab mafodotin) after administration of GSK'916 (belantamab mafodotin) in combination with GSK3359609 will be evaluated.
  • DE Phase: Concentration of ADAs against GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) [ Time Frame: Up to 36 months ]
    Concentration of ADAs against GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) will be evaluated.
  • DE Phase: Concentration of ADAs against GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) [ Time Frame: Up to 36 months ]
    Concentration of ADAs against GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) will be evaluated.
  • DE Phase: Number of participants with adverse events of special interest (AESI) for GSK'916 (belantamab mafodotin) when given in combination with GSK3174998 [ Time Frame: Up to 36 months ]
    An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AESI for GSK'916 (belantamab mafodotin) are corneal events, thrombocytopenia and infusion related reactions. The AESI will be graded utilizing the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0.
  • DE Phase: Number of participants with AESI for GSK'916 (belantamab mafodotin) when given in combination with GSK3359609 [ Time Frame: Up to 36 months ]
    An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AESI for GSK'916 (belantamab mafodotin) are corneal events, thrombocytopenia and infusion related reactions. The AESI will be graded utilizing the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0.
  • DE Phase: Number of participants with AESI for GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) [ Time Frame: Up to 36 months ]
    An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AESI for partner anti-cancer treatment drug when administered in combination with GSK'916 (belantamab mafodotin) will be evaluated.
  • DE Phase: Number of participants with AESI for GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) [ Time Frame: Up to 36 months ]
    An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AESI for partner anti-cancer treatment drug when administered in combination with GSK'916 (belantamab mafodotin) will be evaluated.
  • DE Phase: Number of participants with abnormal ocular findings on ophthalmic examination [ Time Frame: Up to 36 months ]
    A continuous every 21 days ophthalmic examination up to 36 months for all participants will include best corrected visual acuity (BCVA), documentation of manifest refraction used to obtain BCVA, current glasses prescription (if applicable), pupillary exam, intraocular pressure measurement and time checked, full anterior segment examination including fluorescein staining of the cornea, anterior segment exam (slit lamp) includes: orbit/lids/adnexa, conjunctiva, sclera, cornea, anterior chamber, iris, lens and anterior vitreous, anterior segment photography of a fluorescein stained cornea, and dilated funduscopic exam: fundus photography with interpretation.
  • CE Phase: Number of participants achieving Clinical Benefit Rate (CBR) [ Time Frame: Up to 36 months ]
    CBR is defined as the percentage of participants with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents.
  • CE Phase: Number of participants achieving Progression-free survival (PFS) [ Time Frame: Up to 36 months ]
    PFS is defined as the time from randomization until the earliest date of confirmed progressive disease (PD) per IMWG, or death due to any cause.
  • CE Phase: Duration of response (DoR) after administration of GSK'916 (belantamab mafodotin) in combination with GSK3174998 [ Time Frame: Up to 36 months ]
    DoR is defined as the time from first documented evidence or PR or better until progressive disease per IMWG or death due to progressive disease among participants who achieve confirmed partial response or better.
  • CE Phase: DoR after administration of GSK'916 (belantamab mafodotin) in combination with GSK3359609 [ Time Frame: Up to 36 months ]
    DoR is defined as the time from first documented evidence or PR or better until progressive disease per IMWG or death due to progressive disease among participants who achieve confirmed partial response or better.
  • CE Phase: Time to response (TTR) after administration of GSK'916 (belantamab mafodotin) in combination with GSK3174998 [ Time Frame: Up to 36 months ]
    TTR is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (confirmed PR or better).
  • CE Phase: TTR after administration of GSK'916 (belantamab mafodotin) in combination with GSK3359609 [ Time Frame: Up to 36 months ]
    TTR is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (confirmed PR or better).
  • CE Phase: Number of participants achieving Overall survival (OS) [ Time Frame: Up to 36 months ]
    OS is defined as the time from randomization until death due to any cause.
  • CE Phase: Number of participants with AEs and SAEs [ Time Frame: Up to 36 months ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose; results in death or is life-threatening, or requires inpatient hospitalization or prolongation of existing hospitalization, or results in persistent disability/incapacity, or is a congenital anomaly/birth defect, or other situations where medical or scientific judgment should be exercised in deciding whether SAE reporting is appropriate such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.
  • CE Phase: Number of participants with AEs leading to discontinuation [ Time Frame: Up to 36 months ]
    Number of participants with AEs leading to discontinuation will be evaluated.
  • CE Phase: Number of participants with dose reduction or delay [ Time Frame: Up to 36 months ]
    Number of participants with dose reduction or delay will be evaluated.
  • CE Phase: Number of participants with abnormality in vital signs [ Time Frame: Up to 36 months ]
    Vital sign measurements will include systolic and diastolic blood pressure, temperature, and pulse rate.
  • CE Phase: Number of participants with abnormality in hematology parameters [ Time Frame: Up to 36 months ]
    Blood samples will be collected to evaluate platelet count, RBC count, WBC count (absolute), reticulocyte count, hemoglobin, hematocrit, MCV, MCH, MCHC, neutrophils, lymphocytes, monocytes, eosinophils and basophils.
  • CE Phase: Number of participants with abnormality in clinical chemistry parameters [ Time Frame: Up to 36 months ]
    Blood samples will be collected to evaluate urea nitrogen, creatinine, glucose, sodium, magnesium, potassium, chloride, total carbon dioxide/ bicarbonate, calcium (uncorrected), phosphorous, calcium corrected for albumin, AST, ALT, GGT, alkaline phosphatase, CK, total and direct bilirubin, uric acid, albumin, total Protein and LDH.
  • CE Phase: Number of participants with abnormality in routine urinalysis parameters [ Time Frame: Up to 36 months ]
    Urinalysis parameters will be analyzed including specific gravity, pH, glucose, protein, blood, ketones and spot urine (albumin/creatinine ratio). Microscopic examination will be performed if blood or protein is abnormal.
  • CE Phase: Number of participants with abnormality in electrocardiogram (ECG) parameters [ Time Frame: Up to 36 months ]
    Twelve-lead electrocardiogram will be obtained as outlined using an electrocardiogram machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT intervals (QTc). The QT interval will be corrected for heart rate by Fridericia's formula (QTcF).
  • CE Phase: Number of participants with AESI for GSK'916 (belantamab mafodotin) when given in combination with GSK3174998 [ Time Frame: Up to 36 months ]
    An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AESI for GSK'916 (belantamab mafodotin) are corneal events, thrombocytopenia and infusion related reactions. The AESI will be graded utilizing the NCI-CTCAE version 5.0.
  • CE Phase: Number of participants with AESI for GSK'916 (belantamab mafodotin) when given in combination with GSK3359609 [ Time Frame: Up to 36 months ]
    An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AESI for GSK'916 (belantamab mafodotin) are corneal events, thrombocytopenia and infusion related reactions. The AESI will be graded utilizing the NCI-CTCAE version 5.0.
  • CE Phase: Number of participants with AESI for GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) [ Time Frame: Up to 36 months ]
    An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AESI for partner anti-cancer treatment drug when administered in combination with GSK'916 (belantamab mafodotin) will be evaluated.
  • CE Phase: Number of participants with AESI for GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) [ Time Frame: Up to 36 months ]
    An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AESI for partner anti-cancer treatment drug when administered in combination with GSK'916 (belantamab mafodotin) will be evaluated.
  • CE Phase: Number of participants with abnormal ocular findings on ophthalmic examination [ Time Frame: Up to 36 months ]
    A continuous every 21 days ophthalmic examination up to 36 months for all participants will include BCVA, documentation of manifest refraction used to obtain BCVA, current glasses prescription (if applicable), pupillary exam, intraocular pressure measurement and time checked, full anterior segment examination including fluorescein staining of the cornea, anterior segment exam (slit lamp) includes: orbit/lids/adnexa, conjunctiva, sclera, cornea, anterior chamber, iris, lens and anterior vitreous, anterior segment photography of a fluorescein stained cornea, and dilated funduscopic exam: fundus photography with interpretation.
  • CE Phase: Concentration observed of GSK'916 (belantamab mafodotin) when administered in combination with GSK3174998 [ Time Frame: Up to 36 months ]
    The exposure of GSK'916 (belantamab mafodotin) when administered in combination with GSK3174998 in participants with RRMM will be evaluated. The concentration of GSK'916 (belantamab mafodotin) will be analyzed using a population pharmacokinetic approach.
  • CE Phase: Concentration observed of GSK'916 (belantamab mafodotin) when administered in combination with GSK3359609 [ Time Frame: Up to 36 months ]
    The exposure of GSK'916 (belantamab mafodotin) when administered in combination with GSK3359609 in participants with RRMM will be evaluated. The concentration of GSK'916 (belantamab mafodotin) will be analyzed using a population pharmacokinetic approach.
  • CE Phase: Concentration observed of GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) [ Time Frame: Up to 36 months ]
    The exposure of GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) in participants with RRMM will be evaluated. The concentration of GSK3174998 will be analyzed using a population pharmacokinetic approach.
  • CE Phase: Concentration observed of GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) [ Time Frame: Up to 36 months ]
    The exposure of GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) in participants with RRMM will be evaluated. The concentration of GSK3359609 will be analyzed using a population pharmacokinetic approach.
  • CE Phase: Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with GSK3174998 [ Time Frame: Up to 36 months ]
    Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with GSK3174998 will be evaluated.
  • CE Phase: Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with GSK3359609 [ Time Frame: Up to 36 months ]
    Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with GSK3359609 will be evaluated.
  • CE Phase: Concentration of ADAs against GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) [ Time Frame: Up to 36 months ]
    Concentration of ADAs against GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) will be evaluated.
  • CE Phase: Concentration of ADAs against GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) [ Time Frame: Up to 36 months ]
    Concentration of ADAs against GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) will be evaluated.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM 5)
Official Title  ICMJE A Phase I/II, Randomized, Open-label Platform Study Utilizing a Master Protocol to Study Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Anti-Cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) - DREAMM 5
Brief Summary B-cell maturation antigen (BCMA) is a target present on tumor cells in participants with multiple myeloma. Belantamab mafodotin (GSK2857916); is an antibody-drug conjugate (ADC) containing humanized anti-BCMA monoclonal antibody (mAb). This is a phase I/II, randomized, open-label, platform study designed to evaluate the effects of belantamab mafodotin in combination with other anti-cancer drugs in participants with relapsed/refractory multiple myeloma. The Platform design incorporates a single master protocol, where multiple treatment combinations, as sub-studies, will be evaluated simultaneously.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
There will be a dose exploration (DE) phase which will evaluate the safety and tolerability profile of belantamab mafodotin when administered in combination with other anti-cancer treatments. A recommended Phase 2 dose (RP2D) for each combination treatment will be identified based on the safety and preliminary efficacy in DE. This will be followed by a cohort expansion (CE) phase which will evaluate the clinical activity of the combination treatment in comparison to belantamab mafodotin monotherapy in additional participants.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Belantamab mafodotin
    Belantamab mafodotin is available as powder for solution for infusion in unit dose strength of 100 milligram (mg) per vial. It will be delivered as intravenous solution.
  • Drug: GSK3174998
    GSK3174998 is available as powder for solution for infusion in unit dose strength of 40 mg per vial. It will be delivered as intravenous solution.
  • Drug: GSK3359609
    GSK3359609 is available as aqueous solution in unit dose strength of 10 mg per milliliter (mL). It will be delivered as intravenous solution.
  • Drug: Nirogacestat
    Nirogacestat is available as 50 mg tablet. It will be administered orally twice per day.
  • Drug: Dostarlimab
    Dostarlimab will be administered as a 30 minutes intravenous infusion.
Study Arms  ICMJE
  • Experimental: Belantamab mafodotin+GSK3174998 dose exploration (Sub-study 1)
    Interventions:
    • Drug: Belantamab mafodotin
    • Drug: GSK3174998
  • Experimental: Belantamab mafodotin+GSK3359609 dose exploration (Sub-study 2)
    Interventions:
    • Drug: Belantamab mafodotin
    • Drug: GSK3359609
  • Experimental: Belantamab mafodotin+nirogacestat dose exploration(Sub-study3)
    Interventions:
    • Drug: Belantamab mafodotin
    • Drug: Nirogacestat
  • Experimental: Belantamab mafodotin+dostarlimab dose exploration(Sub-study 4)
    Interventions:
    • Drug: Belantamab mafodotin
    • Drug: Dostarlimab
  • Active Comparator: Belantamab mafodotin monotherapy cohort expansion
    Intervention: Drug: Belantamab mafodotin
  • Experimental: Belantamab mafodotin+GSK3174998 cohort expansion (Sub-study 1)
    Interventions:
    • Drug: Belantamab mafodotin
    • Drug: GSK3174998
  • Experimental: Belantamab mafodotin+GSK3359609 cohort expansion (Sub-study 2)
    Interventions:
    • Drug: Belantamab mafodotin
    • Drug: GSK3359609
  • Experimental: Belantamab mafodotin+nirogacestat cohort expansion(Sub-study3)
    Interventions:
    • Drug: Belantamab mafodotin
    • Drug: Nirogacestat
  • Experimental: Belantamab mafodotin+dostarlimab cohort expansion(Sub-study4)
    Interventions:
    • Drug: Belantamab mafodotin
    • Drug: Dostarlimab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 11, 2019)
464
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 24, 2028
Estimated Primary Completion Date February 24, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participant must be 18 years of age inclusive or older, at the time of signing the informed consent.
  • Participants must have histologically or cytologically confirmed diagnosis of Multiple Myeloma (MM), as defined by the IMWG.
  • Participants having at least 3 prior lines of prior anti-myeloma treatments including an immunomodulator (IMID) a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody.
  • Participants with a history of autologous stem cell transplant are eligible for study participation when, transplant was >100 days prior to study enrolment and with no active infection(s).
  • Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, unless ECOG less than equal to (<=)2 is due solely to skeletal complications and/or skeletal pain due to MM.
  • Participants with measurable disease defined as at least one of the following: Serum M-protein greater than equal to (>=)0.5 gram per deciliter (>=5 gram per liter) or Urine M-protein >=200 mg per 24 hours or Serum free light chain (FLC) assay: Involved FLC level >=10 mg per deciliter (>=100 mg per Liter) and an abnormal serum FLC ratio (<0.26 or >1.65).

Exclusion Criteria:

  • Participants with current corneal epithelial disease except mild punctate keratopathy.
  • Participants with evidence of cardiovascular risk
  • Participants with known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin or any of the components of the study treatment. History of severe hypersensitivity to other mAb.
  • Participants with active infection requiring antibiotic, antiviral, or antifungal treatment.
  • Participants with other monoclonal antibodies within 30 days or systemic anti-myeloma therapy within <14 days.
  • Participants with prior radiotherapy within 2 weeks of start of study therapy.
  • Participants with prior allogeneic transplant are prohibited.
  • Participants who have received prior Chimeric Antigen T cell therapy (CAR-T) therapy with lymphodepletion with chemotherapy within 3 months of screening.
  • Participants with any major surgery (other than bone-stabilizing surgery) within the last 30 days.
  • Participants with prior treatment with an investigational agent within 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is shorter.
  • Participants with >=grade 3 toxicity considered related to prior check-point inhibitors and that led to treatment discontinuation.
  • Participants who have received transfusion of blood products within 2 weeks before the first dose of study drug.
  • Participants must not receive live attenuated vaccines within 30 days prior to first dose of study treatment or whilst receiving belantamab mafodotin +- partner agent in any sub-study arm of the platform trial and for at least 70 days following last study treatment.

Additional Exclusion Criteria for Sub-study 1 and Sub-study 2:

  • Participants with autoimmune disease (current or history) or syndrome that required systemic treatment within the past 2 years.
  • Exclusion for a recent (within the past 6 months) history of symptomatic pericarditis.

Additional Exclusion Criteria for Sub-study 3:

  • Participants with uncontrolled small and/or large intestinal disease.
  • Participants with uncontrolled skin disease.
  • Participants with any condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement.
  • Participants with previous administration of a gamma secretase inhibitor.
  • Participants with concomitant administration of a strong or moderate CYP3A4 inhibitor or inducer.

Additional Exclusion Criteria for Sub-study 4:

  • Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
  • Participants who have received prior therapy with an anti-programmed death-1 (anti-PD-1), anti-PD-1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent.
  • Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. Use of inhaled steroids, local injection of steroids, and steroid eye drops are allowed.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com
Listed Location Countries  ICMJE Australia,   Canada,   Netherlands,   Spain,   Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04126200
Other Study ID Numbers  ICMJE 208887
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (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.
URL: http://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP