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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 : April 9, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: GSK'916 (belantamab mafodotin) Drug: GSK3174998 Drug: GSK3359609 Drug: Nirogacestat Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 464 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: There will be a DE phase which will evaluate the safety and tolerability profile of GSK'916 (belantamab mafodotin) when administered in combination with other anti-cancer treatments. A RP2D for each combination treatment will be identified based on the safety and preliminary efficacy in DE. This will be followed by a CE phase which will evaluate the clinical activity of the combination treatment in comparison to GSK'916 (belantamab mafodotin) monotherapy in additional participants.
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : October 7, 2019
Estimated Primary Completion Date : February 21, 2025
Estimated Study Completion Date : February 23, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
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.
Drug: 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.

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.

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.
Drug: 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.

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.

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.
Drug: 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.

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.

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.
Drug: 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.

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.

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]).
Drug: 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.

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

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.
Drug: 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.

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

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.
Drug: 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.

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.
Drug: 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.

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.
Drug: 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.

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.
Drug: 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.

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.
Drug: 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.

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

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]).
Drug: 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.

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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. 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.

  7. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. DE Phase: Number of participants achieving Partial Response (PR) [ Time Frame: Up to 36 months ]
    Number of participants with PR according to IMWG criteria will be analyzed.

  4. DE 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.

  5. DE Phase: Number of participants achieving Complete Response (CR) [ Time Frame: Up to 36 months ]
    Participants with CR according to IMWG criteria will be analyzed.

  6. DE 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.

  7. DE Phase: GSK'916 (belantamab mafodotin) concentration 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.

  8. DE Phase: GSK'916 (belantamab mafodotin) concentration 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.

  9. DE Phase: GSK'916 (belantamab mafodotin) concentration when administered in combination with nirogacestat [ Time Frame: Up to 36 months ]
    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.

  10. DE Phase: GSK3174998 concentration 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.

  11. DE Phase: GSK3359609 concentration 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.

  12. DE Phase: Nirogacestat concentration when administered in combination with GSK'916 (belantamab mafodotin) [ Time Frame: Up to 36 months ]
    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.

  13. 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.

  14. 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.

  15. DE Phase: Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with nirogacestat [ Time Frame: Up to 36 months ]
    Concentration of ADAs against GSK'916 (belantamab mafodotin) after administration of GSK'916 (belantamab mafodotin) in combination with nirogacestat will be evaluated.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. DE Phase: Number of participants with AESI for GSK'916 (belantamab mafodotin) when given in combination with nirogacestat [ 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.

  21. 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.

  22. 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.

  23. DE Phase: Number of participants with AESI for nirogacestat 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.

  24. 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.

  25. 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.

  26. 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.

  27. 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.

  28. CE Phase: DoR after administration of GSK'916 (belantamab mafodotin) in combination with nirogacestat [ 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.

  29. 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).

  30. 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).

  31. CE Phase: TTR after administration of GSK'916 (belantamab mafodotin) in combination with nirogacestat [ 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).

  32. CE Phase: Number of participants achieving PR [ Time Frame: Up to 36 months ]
    Number of participants with PR according to IMWG criteria will be analyzed.

  33. CE Phase: Number of participants achieving VGPR [ Time Frame: Up to 36 months ]
    Number of participants with VGPR according to IMWG criteria will be analyzed.

  34. CE Phase: Number of participants achieving CR [ Time Frame: Up to 36 months ]
    Number of participants with CR according to IMWG criteria will be analyzed.

  35. CE Phase: Number of participants achieving sCR [ Time Frame: Up to 36 months ]
    Number of participants with sCR according to IMWG criteria will be analyzed.

  36. 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.

  37. 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.

  38. 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.

  39. 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.

  40. 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.

  41. 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.

  42. 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.

  43. 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.

  44. 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).

  45. 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.

  46. 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.

  47. CE Phase: Number of participants with AESI for GSK'916 (belantamab mafodotin) when given in combination with nirogacestat [ 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.

  48. 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.

  49. 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.

  50. CE Phase: Number of participants with AESI for nirogacestat 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.

  51. 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.

  52. 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.

  53. 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.

  54. CE Phase: Concentration observed of GSK'916 (belantamab mafodotin) when administered in combination with nirogacestat [ Time Frame: Up to 36 months ]
    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.

  55. 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.

  56. 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.

  57. CE Phase: Concentration observed of nirogacestat 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 nirogacestat will be analyzed using a population pharmacokinetic approach.

  58. 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.

  59. 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.

  60. CE Phase: Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with nirogacestat [ Time Frame: Up to 36 months ]
    Concentration of ADAs against GSK'916 (belantamab mafodotin) when administered in combination with nirogacestat will be evaluated.

  61. 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.

  62. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04126200


Contacts
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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

Locations
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United States, Georgia
GSK Investigational Site Recruiting
Atlanta, Georgia, United States, 30322
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Ajay Nooka         
United States, Wisconsin
GSK Investigational Site Recruiting
Madison, Wisconsin, United States, 53792
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Natalie Callander         
Australia, Victoria
GSK Investigational Site Recruiting
Fitzroy, Victoria, Australia, 3065
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Hang Quach         
GSK Investigational Site Recruiting
Melbourne, Victoria, Australia, 3000
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: David Routledge         
Canada, British Columbia
GSK Investigational Site Recruiting
Vancouver, British Columbia, Canada, V5Z1M9
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Kevin Song         
Canada, Ontario
GSK Investigational Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Suzanne Trudel         
Netherlands
GSK Investigational Site Recruiting
Utrecht, Netherlands, 3584 CX
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Monique C. Minnema         
Spain
GSK Investigational Site Recruiting
Madrid, Spain, 28027
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Paula Rodriguez Otero         
GSK Investigational Site Recruiting
Pamplona, Spain, 31008
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Paula Rodriguez Otero         
Sweden
GSK Investigational Site Recruiting
Stockholm, Sweden, SE-171 64
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Hareth Nahi         
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04126200    
Other Study ID Numbers: 208887
First Posted: October 15, 2019    Key Record Dates
Last Update Posted: April 9, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints 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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
a(OX40)
a(ICOS)
Belantamab mafodotin
gamma-secretase inhibitor
GSK2857916
GSK3174998
GSK3359609
nirogacestat
Platform study
Relapsed/Refractory Multiple Myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases