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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04126200




Registration number
NCT04126200
Ethics application status
Date submitted
11/10/2019
Date registered
15/10/2019
Date last updated
9/04/2020

Titles & IDs
Public title
Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM 5)
Scientific title
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
Secondary ID [1] 0 0
208887
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - GSK'916 (belantamab mafodotin)
Treatment: Drugs - GSK3174998
Treatment: Drugs - GSK3359609
Treatment: Drugs - Nirogacestat

Experimental: Belantamab mafodotin+GSK3174998 dose exploration (Sub-study 1) - This arm will involve the administration of the starting dose (SD) to 3 participants. If the safety profile in the first 3 participants is estimated to be favorable then up to an additional 7 participants will be recruited into the SD group. Both GSK'916 (belantamab mafodotin) and GSK3174998 will be administered to participants via intravenous (IV) infusion on Day 1 of every 21 day cycle. GSK'916 (belantamab mafodotin) (calculated dose as milligram [mg] per kilogram [kg]) will be administered 1 hour before administration of GSK3174998 (fixed dose) at the study site.

Experimental: Belantamab mafodotin+GSK3174998 dose escalation (Sub-study 1) - This arm will involve the administration of 1 or more escalating dose levels. Each dose escalation (DESC) cohort will consist of at least 3 participants, and up to 10 participants. If the safety profile in these first 3 participants in the dose escalation cohort is deemed to be favorable, then up to an additional 7 participants may be recruited. Both belantamab mafodotin and GSK3174998 will be administered to participants via IV infusion on Day 1 of every 21 day cycle. Belantamab mafodotin (calculated dose as mg per kg) will be administered 1 hour before administration of GSK3174998 (fixed dose) at the study site. If the combination is not considered safe, then the dose of either belantamab mafodotin or GSK3174998 can be de-escalated.

Experimental: Belantamab mafodotin+GSK3359609 dose exploration (Sub-study 2) - This arm will involve the administration of the SD to 3 participants. If the safety profile in the first 3 participants is estimated to be favorable, then up to an additional 7 participants will be recruited into the SD group. Both GSK'916 (belantamab mafodotin) and GSK3359609 will be administered to participants via IV infusion on Day 1 of every 21 day cycle. GSK'916 (belantamab mafodotin) (calculated dose as mg per kg) will be administered 1 hour before administration of GSK3359609 (fixed dose) at the study site.

Experimental: Belantamab mafodotin+GSK3359609 dose escalation (Sub-study 2) - This arm will involve the administration of 1 or more escalating dose levels. Each DESC cohort will consist of at least 3 participants, and up to 10 participants. If the safety profile in these first 3 participants in the DESC cohort is deemed to be favorable, then up to an additional 7 participants may be recruited. Both GSK'916 (belantamab mafodotin) and GSK3359609 will be administered to participants via IV infusion on Day 1 of every 21 day cycle. GSK'916 (belantamab mafodotin) (calculated dose as mg per kg) will be administered 1 hour before administration of GSK3359609 (fixed dose) at the study site. If the combination is not considered safe, then the dose of either GSK'916 (belantamab mafodotin) or GSK3359609 can be de-escalated.

Experimental: Belantamab mafodotin+nirogacestat dose exploration(Sub-study3) - This arm will involve the administration of the starting dose (SD) to 3 participants. If the safety profile in the first 3 participants is estimated to be favorable then up to an additional 7 participants will be recruited into the SD group. GSK'916 (belantamab mafodotin) will be administered to participants via IV infusion and nirogacestat will be administered orally twice a day for 21 days and the first dose is administered at the study site one hour before GSK'916 (belantamab mafodotin) (calculated dose as milligram [mg] per kilogram [kg]).

Active Comparator: Belantamab mafodotin+nirogacestat dose escalation(Sub-study3) - In the CE phase, there is a 2 part randomization. Participants will be randomized into a sub-study and then within a sub-study to receive either the contemporaneous GSK'916 (belantamab mafodotin) monotherapy control or the RP2D of the combination treatment. Within a sub-study, participants will be randomized to receive GSK'916 (belantamab mafodotin) monotherapy IV on day 1 of each 21-day cycle. GSK'916 (belantamab mafodotin) will be administered to participants intravenously (calculated dose as mg per kg) at the study site. The intended cycle time of GSK'916 (belantamab mafodotin) as a monotherapy is 21 days (-3 day window) and cannot occur more frequently than this.

Active Comparator: Belantamab mafodotin monotherapy cohort expansion (Sub-study1) - In the CE phase, there is a 2 part randomization. Participants will be randomized into a sub-study and then within a sub-study to receive either the contemporaneous GSK'916 (belantamab mafodotin) monotherapy control or the RP2D of the combination treatment. Within a sub-study, participants will be randomized to receive GSK'916 (belantamab mafodotin) monotherapy IV on day 1 of each 21-day cycle. GSK'916 (belantamab mafodotin) will be administered to participants intravenously (calculated dose as mg per kg) at the study site. The intended cycle time of GSK'916 (belantamab mafodotin) as a monotherapy is 21 days (-3 day window) and cannot occur more frequently than this.

Experimental: Belantamab mafodotin+GSK3174998 cohort expansion (Sub-study 1) - Within a sub-study, participants will be randomized to receive the RP2D of the combination of GSK'916 (belantamab mafodotin) plus GSK3174998 to further assess the additional clinical benefit and safety. Both GSK'916 (belantamab mafodotin) and GSK3174998 will be administered to participants via IV infusion on Day 1 of every 21 day cycle. GSK'916 (belantamab mafodotin) (calculated dose as mg per kg) will be administered 1 hour before administration of GSK3174998 (fixed dose) at the study site.

Active Comparator: Belantamab mafodotin monotherapy cohort expansion (Sub-study2) - Within a sub-study, participants will be randomized to receive GSK'916 (belantamab mafodotin) monotherapy IV on day 1 of each 21-day cycle. GSK'916 (belantamab mafodotin) will be administered to participants intravenously (calculated dose as mg per kg) at the study site. The intended cycle time of GSK'916 (belantamab mafodotin) as a monotherapy is 21 days (-3 day window) and cannot occur more frequently than this.

Experimental: Belantamab mafodotin+GSK3359609 cohort expansion (Sub-study 2) - Within a sub-study, participants will be randomized to receive the RP2D of the combination of GSK'916 (belantamab mafodotin) plus GSK3359609 to further assess the additional clinical benefit and safety. Both GSK'916 (belantamab mafodotin) and GSK3359609 will be administered to participants via IV infusion on Day 1 of every 21 day cycle. GSK'916 (belantamab mafodotin) (calculated dose as mg per kg) will be administered 1 hour before administration of GSK3359609 (fixed dose) at the study site.

Active Comparator: Belantamab mafodotin monotherapy cohort expansion(Sub-study3) - In the CE phase, there is a 2 part randomization. Participants will be randomized into a sub-study and then within a sub-study to receive either the contemporaneous GSK'916 (belantamab mafodotin) monotherapy control or the RP2D of the combination treatment. Within a sub-study, participants will be randomized to receive GSK'916 (belantamab mafodotin) monotherapy IV on day 1 of each 21-day cycle. GSK'916 (belantamab mafodotin) will be administered to participants intravenously (calculated dose as mg per kg) at the study site. The intended cycle time of GSK'916 (belantamab mafodotin) as a monotherapy is 21 days (-3 day window) and cannot occur more frequently than this.

Experimental: Belantamab mafodotin+nirogacestat cohort exploration Substudy3 - Within a sub-study, participants will be randomized to receive the RP2D of the combination of GSK'916 (belantamab mafodotin) plus nirogacestat to further assess the additional clinical benefit and safety. GSK'916 (belantamab mafodotin) will be administered to participants via IV infusion and nirogacestat will be administered orally twice a day for 21 days and the first dose is administered at the study site one hour before GSK'916 (belantamab mafodotin) (calculated dose as milligram [mg] per kilogram [kg]).


Treatment: Drugs: GSK'916 (belantamab mafodotin)
GSK'916 (belantamab mafodotin) is available as powder for solution for infusion in unit dose strength of 100 mg per vial. It will be delivered as intravenous solution.

Treatment: Drugs: 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.

Treatment: Drugs: GSK3359609
GSK3359609 is available as aqueous solution in unit dose strength of 10 mg per milliliter (mL). It will be delivered as intravenous solution.

Treatment: Drugs: Nirogacestat
Nirogacestat is available as 50 mg tablet. It will be administered orally twice per day.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DE Phase: Number of participants achieving dose limiting toxicities (DLT) - 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.
Timepoint [1] 0 0
Up to 36 months
Primary outcome [2] 0 0
DE Phase: Number of participants with adverse events (AEs) and serious adverse events (SAEs) - 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.
Timepoint [2] 0 0
Up to 36 months
Primary outcome [3] 0 0
DE Phase: Number of participants with abnormality in vital signs - Vital sign measurements will include systolic and diastolic blood pressure, temperature, and pulse rate.
Timepoint [3] 0 0
Up to 36 months
Primary outcome [4] 0 0
DE Phase: Number of participants with abnormality in hematology parameters - 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.
Timepoint [4] 0 0
Up to 36 months
Primary outcome [5] 0 0
DE Phase: Number of participants with abnormality in clinical chemistry parameters - 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).
Timepoint [5] 0 0
Up to 36 months
Primary outcome [6] 0 0
DE Phase: Number of participants with abnormality in routine urinalysis parameters - 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.
Timepoint [6] 0 0
Up to 36 months
Primary outcome [7] 0 0
CE Phase: Number of participants achieving Overall Response Rate (ORR) - 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.
Timepoint [7] 0 0
Up to 36 months
Secondary outcome [1] 0 0
DE Phase: Number of participants achieving ORR - ORR is defined as the percentage of participants with PR or better, according to the IMWG Response Criteria.
Timepoint [1] 0 0
Up to 36 months
Secondary outcome [2] 0 0
CE Phase: Number of participants achieving Clinical Benefit Rate (CBR) - 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.
Timepoint [2] 0 0
Up to 36 months
Secondary outcome [3] 0 0
DE Phase: Number of participants achieving Partial Response (PR) - Number of participants with PR according to IMWG criteria will be analyzed.
Timepoint [3] 0 0
Up to 36 months
Secondary outcome [4] 0 0
DE Phase: Number of participants achieving Very Good Partial Response (VGPR) - Number of participants with VGPR according to IMWG criteria will be analyzed.
Timepoint [4] 0 0
Up to 36 months
Secondary outcome [5] 0 0
DE Phase: Number of participants achieving Complete Response (CR) - Participants with CR according to IMWG criteria will be analyzed.
Timepoint [5] 0 0
Up to 36 months
Secondary outcome [6] 0 0
DE Phase: Number of participants achieving stringent Complete Response (sCR) - Participants with sCR according to IMWG criteria will be analyzed.
Timepoint [6] 0 0
Up to 36 months
Secondary outcome [7] 0 0
DE Phase: GSK'916 (belantamab mafodotin) concentration when administered in combination with GSK3174998 - 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.
Timepoint [7] 0 0
Up to 36 months
Secondary outcome [8] 0 0
DE Phase: GSK'916 (belantamab mafodotin) concentration when administered in combination with GSK3359609 - 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.
Timepoint [8] 0 0
Up to 36 months
Secondary outcome [9] 0 0
DE Phase: GSK'916 (belantamab mafodotin) concentration when administered in combination with nirogacestat - The exposure of GSK'916 (belantamab mafodotin) when administered in combination nirogacestat in participants with RRMM will be evaluated. The concentration of GSK'916 (belantamab mafodotin) will be analyzed using a population pharmacokinetic approach.
Timepoint [9] 0 0
Up to 36 months
Secondary outcome [10] 0 0
DE Phase: GSK3174998 concentration when administered in combination with GSK'916 (belantamab mafodotin) - 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.
Timepoint [10] 0 0
Up to 36 months
Secondary outcome [11] 0 0
DE Phase: GSK3359609 concentration when administered in combination with GSK'916 (belantamab mafodotin) - 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.
Timepoint [11] 0 0
Up to 36 months
Secondary outcome [12] 0 0
DE Phase: Nirogacestat concentration when administered in combination with GSK'916 (belantamab mafodotin) - The exposure of nirogacestat when administered in combination with GSK'916 (belantamab mafodotin) in participants with RRMM will be evaluated. The concentration of nirogacestat will be analyzed using a population pharmacokinetic approach.
Timepoint [12] 0 0
Up to 36 months
Secondary outcome [13] 0 0
DE Phase: Concentration of anti-drug antibodies (ADAs) against GSK'916 (belantamab mafodotin) when administered in combination with GSK3174998 - Concentration of ADAs against GSK'916 (belantamab mafodotin) after administration of GSK'916 (belantamab mafodotin) in combination with GSK3174998 will be evaluated.
Timepoint [13] 0 0
Up to 36 months
Secondary outcome [14] 0 0
DE Phase: Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with GSK3359609 - Concentration of ADAs against GSK'916 (belantamab mafodotin) after administration of GSK'916 (belantamab mafodotin) in combination with GSK3359609 will be evaluated.
Timepoint [14] 0 0
Up to 36 months
Secondary outcome [15] 0 0
DE Phase: Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with nirogacestat - Concentration of ADAs against GSK'916 (belantamab mafodotin) after administration of GSK'916 (belantamab mafodotin) in combination with nirogacestat will be evaluated.
Timepoint [15] 0 0
Up to 36 months
Secondary outcome [16] 0 0
DE Phase: Concentration of ADAs against GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) - Concentration of ADAs against GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) will be evaluated.
Timepoint [16] 0 0
Up to 36 months
Secondary outcome [17] 0 0
DE Phase: Concentration of ADAs against GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) - Concentration of ADAs against GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) will be evaluated.
Timepoint [17] 0 0
Up to 36 months
Secondary outcome [18] 0 0
DE Phase: Number of participants with adverse events of special interest (AESI) for GSK'916 (belantamab mafodotin) when given in combination with GSK3174998 - 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.
Timepoint [18] 0 0
Up to 36 months
Secondary outcome [19] 0 0
DE Phase: Number of participants with AESI for GSK'916 (belantamab mafodotin) when given in combination with GSK3359609 - 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.
Timepoint [19] 0 0
Up to 36 months
Secondary outcome [20] 0 0
DE Phase: Number of participants with AESI for GSK'916 (belantamab mafodotin) when given in combination with nirogacestat - 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.
Timepoint [20] 0 0
Up to 36 months
Secondary outcome [21] 0 0
DE Phase: Number of participants with AESI for GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) - 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.
Timepoint [21] 0 0
Up to 36 months
Secondary outcome [22] 0 0
DE Phase: Number of participants with AESI for GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) - 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.
Timepoint [22] 0 0
Up to 36 months
Secondary outcome [23] 0 0
DE Phase: Number of participants with AESI for nirogacestat when administered in combination with GSK'916 (belantamab mafodotin) - 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.
Timepoint [23] 0 0
Up to 36 months
Secondary outcome [24] 0 0
DE Phase: Number of participants with abnormal ocular findings on ophthalmic examination - 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.
Timepoint [24] 0 0
Up to 36 months
Secondary outcome [25] 0 0
CE Phase: Number of participants achieving Progression-free survival (PFS) - 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.
Timepoint [25] 0 0
Up to 36 months
Secondary outcome [26] 0 0
CE Phase: Duration of response (DoR) after administration of GSK'916 (belantamab mafodotin) in combination with GSK3174998 - 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.
Timepoint [26] 0 0
Up to 36 months
Secondary outcome [27] 0 0
CE Phase: DoR after administration of GSK'916 (belantamab mafodotin) in combination with GSK3359609 - 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.
Timepoint [27] 0 0
Up to 36 months
Secondary outcome [28] 0 0
CE Phase: DoR after administration of GSK'916 (belantamab mafodotin) in combination with nirogacestat - 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.
Timepoint [28] 0 0
Up to 36 months
Secondary outcome [29] 0 0
CE Phase: Time to response (TTR) after administration of GSK'916 (belantamab mafodotin) in combination with GSK3174998 - 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).
Timepoint [29] 0 0
Up to 36 months
Secondary outcome [30] 0 0
CE Phase: TTR after administration of GSK'916 (belantamab mafodotin) in combination with GSK3359609 - 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).
Timepoint [30] 0 0
Up to 36 months
Secondary outcome [31] 0 0
CE Phase: TTR after administration of GSK'916 (belantamab mafodotin) in combination with nirogacestat - 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).
Timepoint [31] 0 0
Up to 36 months
Secondary outcome [32] 0 0
CE Phase: Number of participants achieving PR - Number of participants with PR according to IMWG criteria will be analyzed.
Timepoint [32] 0 0
Up to 36 months
Secondary outcome [33] 0 0
CE Phase: Number of participants achieving VGPR - Number of participants with VGPR according to IMWG criteria will be analyzed.
Timepoint [33] 0 0
Up to 36 months
Secondary outcome [34] 0 0
CE Phase: Number of participants achieving CR - Number of participants with CR according to IMWG criteria will be analyzed.
Timepoint [34] 0 0
Up to 36 months
Secondary outcome [35] 0 0
CE Phase: Number of participants achieving sCR - Number of participants with sCR according to IMWG criteria will be analyzed.
Timepoint [35] 0 0
Up to 36 months
Secondary outcome [36] 0 0
CE Phase: Number of participants achieving Overall survival (OS) - OS is defined as the time from randomization until death due to any cause.
Timepoint [36] 0 0
Up to 36 months
Secondary outcome [37] 0 0
CE Phase: Number of participants with AEs and SAEs - 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.
Timepoint [37] 0 0
Up to 36 months
Secondary outcome [38] 0 0
CE Phase: Number of participants with AEs leading to discontinuation - Number of participants with AEs leading to discontinuation will be evaluated.
Timepoint [38] 0 0
Up to 36 months
Secondary outcome [39] 0 0
CE Phase: Number of participants with dose reduction or delay - Number of participants with dose reduction or delay will be evaluated.
Timepoint [39] 0 0
Up to 36 months
Secondary outcome [40] 0 0
CE Phase: Number of participants with abnormality in vital signs - Vital sign measurements will include systolic and diastolic blood pressure, temperature, and pulse rate.
Timepoint [40] 0 0
Up to 36 months
Secondary outcome [41] 0 0
CE Phase: Number of participants with abnormality in hematology parameters - 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.
Timepoint [41] 0 0
Up to 36 months
Secondary outcome [42] 0 0
CE Phase: Number of participants with abnormality in clinical chemistry parameters - 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.
Timepoint [42] 0 0
Up to 36 months
Secondary outcome [43] 0 0
CE Phase: Number of participants with abnormality in routine urinalysis parameters - 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.
Timepoint [43] 0 0
Up to 36 months
Secondary outcome [44] 0 0
CE Phase: Number of participants with abnormality in electrocardiogram (ECG) parameters - 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).
Timepoint [44] 0 0
Up to 36 months
Secondary outcome [45] 0 0
CE Phase: Number of participants with AESI for GSK'916 (belantamab mafodotin) when given in combination with GSK3174998 - 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.
Timepoint [45] 0 0
Up to 36 months
Secondary outcome [46] 0 0
CE Phase: Number of participants with AESI for GSK'916 (belantamab mafodotin) when given in combination with GSK3359609 - 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.
Timepoint [46] 0 0
Up to 36 months
Secondary outcome [47] 0 0
CE Phase: Number of participants with AESI for GSK'916 (belantamab mafodotin) when given in combination with nirogacestat - 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.
Timepoint [47] 0 0
Up to 36 months
Secondary outcome [48] 0 0
CE Phase: Number of participants with AESI for GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) - 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.
Timepoint [48] 0 0
Up to 36 months
Secondary outcome [49] 0 0
CE Phase: Number of participants with AESI for GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) - 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.
Timepoint [49] 0 0
Up to 36 months
Secondary outcome [50] 0 0
CE Phase: Number of participants with AESI for nirogacestat when administered in combination with GSK'916 (belantamab mafodotin) - 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.
Timepoint [50] 0 0
Up to 36 months
Secondary outcome [51] 0 0
CE Phase: Number of participants with abnormal ocular findings on ophthalmic examination - 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.
Timepoint [51] 0 0
Up to 36 months
Secondary outcome [52] 0 0
CE Phase: Concentration observed of GSK'916 (belantamab mafodotin) when administered in combination with GSK3174998 - 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.
Timepoint [52] 0 0
Up to 36 months
Secondary outcome [53] 0 0
CE Phase: Concentration observed of GSK'916 (belantamab mafodotin) when administered in combination with GSK3359609 - 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.
Timepoint [53] 0 0
Up to 36 months
Secondary outcome [54] 0 0
CE Phase: Concentration observed of GSK'916 (belantamab mafodotin) when administered in combination with nirogacestat - The exposure of GSK'916 (belantamab mafodotin) when administered in combination with nirogacestat in participants with RRMM will be evaluated. The concentration of GSK'916 (belantamab mafodotin) will be analyzed using a population pharmacokinetic approach.
Timepoint [54] 0 0
Up to 36 months
Secondary outcome [55] 0 0
CE Phase: Concentration observed of GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) - 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.
Timepoint [55] 0 0
Up to 36 months
Secondary outcome [56] 0 0
CE Phase: Concentration observed of GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) - 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.
Timepoint [56] 0 0
Up to 36 months
Secondary outcome [57] 0 0
CE Phase: Concentration observed of nirogacestat when administered in combination with GSK'916 (belantamab mafodotin) - The exposure of GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) in participants with RRMM will be evaluated. The concentration of nirogacestat will be analyzed using a population pharmacokinetic approach.
Timepoint [57] 0 0
Up to 36 months
Secondary outcome [58] 0 0
CE Phase: Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with GSK3174998 - Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with GSK3174998 will be evaluated.
Timepoint [58] 0 0
Up to 36 months
Secondary outcome [59] 0 0
CE Phase: Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with GSK3359609 - Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with GSK3359609 will be evaluated.
Timepoint [59] 0 0
Up to 36 months
Secondary outcome [60] 0 0
CE Phase: Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with nirogacestat - Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with nirogacestat will be evaluated.
Timepoint [60] 0 0
Up to 36 months
Secondary outcome [61] 0 0
CE Phase: Concentration of ADAs against GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) - Concentration of ADAs against GSK3174998 when administered in combination with GSK'916 (belantamab mafodotin) will be evaluated.
Timepoint [61] 0 0
Up to 36 months
Secondary outcome [62] 0 0
CE Phase: Concentration of ADAs against GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) - Concentration of ADAs against GSK3359609 when administered in combination with GSK'916 (belantamab mafodotin) will be evaluated.
Timepoint [62] 0 0
Up to 36 months

Eligibility
Key inclusion criteria
- 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 0-2.

- Participants with measurable disease defined as at least one of the following: Serum
M-protein >=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).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 GSK'916 (belantamab mafodotin) or any of the components
of the study treatment. History of severe hypersensitivity to other monoclonal
antibody (mAbs).

- 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.

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.

- Key lifestyle consideration.

- Contact lenses are prohibited while the participant is on study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Fitzroy
Recruitment hospital [2] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
3065 - Fitzroy
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
Wisconsin
Country [3] 0 0
Canada
State/province [3] 0 0
British Columbia
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Netherlands
State/province [5] 0 0
Utrecht
Country [6] 0 0
Spain
State/province [6] 0 0
Madrid
Country [7] 0 0
Spain
State/province [7] 0 0
Pamplona
Country [8] 0 0
Sweden
State/province [8] 0 0
Stockholm

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
B-cell maturation antigen (BCMA) is a target present on tumor cells in participants with
multiple myeloma. Belantamab mafodotin (GSK2857916); also referred to as GSK'916; 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
GSK'916 (belantamab mafodotin) in combination with other anti-cancer drugs in participants
with relapsed/refractory multiple myeloma (RRMM). The Platform design incorporates a single
master protocol, where multiple treatment combinations, as sub-studies, will be evaluated
simultaneously. This study will include two parts; dose exploration (DE) and cohort expansion
(CE). In the DE phase, the safety and tolerability profile of GSK'916 (belantamab mafodotin)
will be evaluated when administered in combination with other anti-cancer agents. This may
identify a recommended phase 2 dose (RP2D) for each partner, as well as efficacy of each
combination. The CE phase of the study will evaluate the clinical activity of the
combinations in comparison to monotherapy in additional participants with RRMM.
Trial website
https://clinicaltrials.gov/show/NCT04126200
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04126200