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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 : August 10, 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); is an antibody-drug conjugate (ADC) containing humanized anti-BCMA monoclonal antibody (mAb). This is a phase I/II, randomized, open-label, platform study designed to evaluate the effects of belantamab mafodotin in combination with other anti-cancer drugs in participants with relapsed/refractory multiple myeloma. The Platform design incorporates a single master protocol, where multiple treatment combinations, as sub-studies, will be evaluated simultaneously.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Belantamab mafodotin Drug: GSK3174998 Drug: GSK3359609 Drug: Nirogacestat Drug: Dostarlimab Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 464 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: There will be a dose exploration (DE) phase which will evaluate the safety and tolerability profile of belantamab mafodotin when administered in combination with other anti-cancer treatments. A recommended Phase 2 dose (RP2D) for each combination treatment will be identified based on the safety and preliminary efficacy in DE. This will be followed by a cohort expansion (CE) phase which will evaluate the clinical activity of the combination treatment in comparison to belantamab mafodotin monotherapy in additional participants.
Masking: None (Open Label)
Primary Purpose: Treatment
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) Drug: Belantamab mafodotin
Belantamab mafodotin is available as powder for solution for infusion in unit dose strength of 100 milligram (mg) per vial. It will be delivered as intravenous solution.

Drug: GSK3174998
GSK3174998 is available as powder for solution for infusion in unit dose strength of 40 mg per vial. It will be delivered as intravenous solution.

Experimental: Belantamab mafodotin+GSK3359609 dose exploration (Sub-study 2) Drug: Belantamab mafodotin
Belantamab mafodotin is available as powder for solution for infusion in unit dose strength of 100 milligram (mg) per vial. It will be delivered as intravenous solution.

Drug: 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) Drug: Belantamab mafodotin
Belantamab mafodotin is available as powder for solution for infusion in unit dose strength of 100 milligram (mg) per vial. It will be delivered as intravenous solution.

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

Experimental: Belantamab mafodotin+dostarlimab dose exploration(Sub-study 4) Drug: Belantamab mafodotin
Belantamab mafodotin is available as powder for solution for infusion in unit dose strength of 100 milligram (mg) per vial. It will be delivered as intravenous solution.

Drug: Dostarlimab
Dostarlimab will be administered as a 30 minutes intravenous infusion.

Active Comparator: Belantamab mafodotin monotherapy cohort expansion Drug: Belantamab mafodotin
Belantamab mafodotin is available as powder for solution for infusion in unit dose strength of 100 milligram (mg) per vial. It will be delivered as intravenous solution.

Experimental: Belantamab mafodotin+GSK3174998 cohort expansion (Sub-study 1) Drug: Belantamab mafodotin
Belantamab mafodotin is available as powder for solution for infusion in unit dose strength of 100 milligram (mg) per vial. It will be delivered as intravenous solution.

Drug: GSK3174998
GSK3174998 is available as powder for solution for infusion in unit dose strength of 40 mg per vial. It will be delivered as intravenous solution.

Experimental: Belantamab mafodotin+GSK3359609 cohort expansion (Sub-study 2) Drug: Belantamab mafodotin
Belantamab mafodotin is available as powder for solution for infusion in unit dose strength of 100 milligram (mg) per vial. It will be delivered as intravenous solution.

Drug: 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 cohort expansion(Sub-study3) Drug: Belantamab mafodotin
Belantamab mafodotin is available as powder for solution for infusion in unit dose strength of 100 milligram (mg) per vial. It will be delivered as intravenous solution.

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

Experimental: Belantamab mafodotin+dostarlimab cohort expansion(Sub-study4) Drug: Belantamab mafodotin
Belantamab mafodotin is available as powder for solution for infusion in unit dose strength of 100 milligram (mg) per vial. It will be delivered as intravenous solution.

Drug: Dostarlimab
Dostarlimab will be administered as a 30 minutes intravenous infusion.




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 ]
    AEs and SAEs will be collected.

  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, respiratory rate and pulse rate.

  4. DE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters [ Time Frame: Up to 36 months ]
    Blood and urine samples will be collected to evaluate hematology, clinical chemistry and urinalysis lab parameters.

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

  4. DE Phase and CE Phase: Number of participants achieving Very Good Partial Response (VGPR) [ Time Frame: Up to 36 months ]
    Number of participants with VGPR according to IMWG criteria will be analyzed.

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

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

  7. DE Phase and CE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments [ Time Frame: Up to 36 months ]
    Blood samples will be collected for concentrations of belantamab mafodotin.

  8. DE Phase and CE Phase: GSK3174998 concentration when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples will be collected for concentrations of GSK3174998.

  9. DE Phase and CE Phase: GSK3359609 concentration when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples will be collected for concentrations of GSK3359609.

  10. DE Phase and CE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples will be collected for concentrations of nirogacestat.

  11. DE Phase and CE Phase: Dostarlimab concentration when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples will be collected for concentrations of dostarlimab.

  12. DE Phase and CE Phase: Concentration of anti-drug antibodies (ADAs) against belantamab mafodotin when administered in combination with anti-cancer treatments [ Time Frame: Up to 36 months ]
    Blood samples for concentrations for ADAs will be collected.

  13. DE Phase and CE Phase: Concentration of ADAs against GSK3174998 when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples for concentrations for ADAs will be collected.

  14. DE Phase and CE Phase: Concentration of ADAs against GSK3359609 when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples for concentrations for ADAs will be collected.

  15. DE Phase and CE Phase: Concentration of ADAs against dostarlimab when administered in combination with belantamab mafodotin [ Time Frame: Up to 36 months ]
    Blood samples for concentrations for ADAs will be collected.

  16. DE Phase and CE Phase: Number of participants with adverse events of special interest (AESI) [ Time Frame: Up to 36 months ]
    AESIs will be collected.

  17. DE Phase and CE Phase: Number of participants with abnormal ocular findings on ophthalmic examination [ Time Frame: Up to 36 months ]
    Ophthalmic examination will assess abnormal findings.

  18. 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.

  19. CE Phase: Duration of response (DoR) [ Time Frame: Up to 36 months ]
    DoR is defined as the time from first documented evidence or PR or better until progressive disease per IMWG or death due to progressive disease among participants who achieve confirmed partial response or better.

  20. CE Phase: Time to response (TTR) [ Time Frame: Up to 36 months ]
    TTR is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (confirmed PR or better).

  21. 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.

  22. CE Phase: Number of participants with AEs and SAEs [ Time Frame: Up to 36 months ]
    AEs and SAEs will be collected.

  23. 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.

  24. 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.

  25. CE Phase: Number of participants with abnormality in vital signs [ Time Frame: Up to 36 months ]
    Vital sign measurements will include systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate.

  26. CE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters [ Time Frame: Up to 36 months ]
    Blood and urine samples will be collected to evaluate hematology, clinical chemistry and urinalysis lab parameters.



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:

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

Exclusion Criteria:

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

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

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

Additional Exclusion Criteria for Sub-study 3:

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

Additional Exclusion Criteria for Sub-study 4:

  • Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
  • Participants who have received prior therapy with an anti-programmed death-1 (anti-PD-1), anti-PD-1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent.
  • Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. Use of inhaled steroids, local injection of steroids, and steroid eye drops are allowed.

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
Amsterdam, Netherlands, 1081 HV
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: Niels W.C.J. van de Donk         
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: August 10, 2020
Last Verified: August 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, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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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:
Belantamab mafodotin
GSK2857916
GSK3174998
GSK3359609
Nirogacestat
Dostarlimab
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