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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)

NCT04126200

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief 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)
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 208887
  • NCT ID: NCT04126200

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
Belantamab mafodotinBelantamab mafodotin monotherapy cohort expansion
GSK3174998Belantamab mafodotin+GSK3174998 cohort expansion (Sub-study 1)
GSK3359609Belantamab mafodotin+GSK3359609 cohort expansion (Sub-study 2)
NirogacestatBelantamab mafodotin+nirogacestat cohort expansion(Sub-study3)
DostarlimabBelantamab mafodotin+dostarlimab cohort expansion(Sub-study4)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Belantamab mafodotin+GSK3174998 dose exploration (Sub-study 1)Experimental
  • Belantamab mafodotin
  • GSK3174998
Belantamab mafodotin+GSK3359609 dose exploration (Sub-study 2)Experimental
  • Belantamab mafodotin
  • GSK3359609
Belantamab mafodotin+nirogacestat dose exploration(Sub-study3)Experimental
  • Belantamab mafodotin
  • Nirogacestat
Belantamab mafodotin+dostarlimab dose exploration(Sub-study 4)Experimental
  • Belantamab mafodotin
  • Dostarlimab
Belantamab mafodotin monotherapy cohort expansionActive Comparator
  • Belantamab mafodotin
Belantamab mafodotin+GSK3174998 cohort expansion (Sub-study 1)Experimental
  • Belantamab mafodotin
  • GSK3174998
Belantamab mafodotin+GSK3359609 cohort expansion (Sub-study 2)Experimental
  • Belantamab mafodotin
  • GSK3359609
Belantamab mafodotin+nirogacestat cohort expansion(Sub-study3)Experimental
  • Belantamab mafodotin
  • Nirogacestat
Belantamab mafodotin+dostarlimab cohort expansion(Sub-study4)Experimental
  • Belantamab mafodotin
  • Dostarlimab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:DE Phase: Number of participants achieving dose limiting toxicities (DLT)
Time Frame:Up to 36 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:DE Phase: Number of participants achieving ORR
Time Frame:Up to 36 months
Safety Issue:
Description:ORR is defined as the percentage of participants with PR or better, according to the IMWG Response Criteria.
Measure:CE Phase: Number of participants achieving Clinical Benefit Rate (CBR)
Time Frame:Up to 36 months
Safety Issue:
Description: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.
Measure:DE Phase and CE Phase: Number of participants achieving Partial Response
Time Frame:Up to 36 months
Safety Issue:
Description:Number of participants with PR according to IMWG criteria will be analyzed.
Measure:DE Phase and CE Phase: Number of participants achieving Very Good Partial Response (VGPR)
Time Frame:Up to 36 months
Safety Issue:
Description:Number of participants with VGPR according to IMWG criteria will be analyzed.
Measure:DE Phase and CE Phase: Number of participants achieving Complete Response (CR)
Time Frame:Up to 36 months
Safety Issue:
Description:Participants with CR according to IMWG criteria will be analyzed.
Measure:DE Phase and CE Phase: Number of participants achieving stringent Complete Response (sCR)
Time Frame:Up to 36 months
Safety Issue:
Description:Participants with sCR according to IMWG criteria will be analyzed.
Measure:DE Phase and CE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments
Time Frame:Up to 36 months
Safety Issue:
Description:Blood samples will be collected for concentrations of belantamab mafodotin.
Measure:DE Phase and CE Phase: GSK3174998 concentration when administered in combination with belantamab mafodotin
Time Frame:Up to 36 months
Safety Issue:
Description:Blood samples will be collected for concentrations of GSK3174998.
Measure:DE Phase and CE Phase: GSK3359609 concentration when administered in combination with belantamab mafodotin
Time Frame:Up to 36 months
Safety Issue:
Description:Blood samples will be collected for concentrations of GSK3359609.
Measure:DE Phase and CE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin
Time Frame:Up to 36 months
Safety Issue:
Description:Blood samples will be collected for concentrations of nirogacestat.
Measure:DE Phase and CE Phase: Dostarlimab concentration when administered in combination with belantamab mafodotin
Time Frame:Up to 36 months
Safety Issue:
Description:Blood samples will be collected for concentrations of dostarlimab.
Measure: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
Safety Issue:
Description:Blood samples for concentrations for ADAs will be collected.
Measure:DE Phase and CE Phase: Concentration of ADAs against GSK3174998 when administered in combination with belantamab mafodotin
Time Frame:Up to 36 months
Safety Issue:
Description:Blood samples for concentrations for ADAs will be collected.
Measure:DE Phase and CE Phase: Concentration of ADAs against GSK3359609 when administered in combination with belantamab mafodotin
Time Frame:Up to 36 months
Safety Issue:
Description:Blood samples for concentrations for ADAs will be collected.
Measure:DE Phase and CE Phase: Concentration of ADAs against dostarlimab when administered in combination with belantamab mafodotin
Time Frame:Up to 36 months
Safety Issue:
Description:Blood samples for concentrations for ADAs will be collected.
Measure:DE Phase and CE Phase: Number of participants with adverse events of special interest (AESI)
Time Frame:Up to 36 months
Safety Issue:
Description:AESIs will be collected.
Measure:DE Phase and CE Phase: Number of participants with abnormal ocular findings on ophthalmic examination
Time Frame:Up to 36 months
Safety Issue:
Description:Ophthalmic examination will assess abnormal findings.
Measure:CE Phase: Number of participants achieving Progression-free survival (PFS)
Time Frame:Up to 36 months
Safety Issue:
Description: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.
Measure:CE Phase: Duration of response (DoR)
Time Frame:Up to 36 months
Safety Issue:
Description: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.
Measure:CE Phase: Time to response (TTR)
Time Frame:Up to 36 months
Safety Issue:
Description: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).
Measure:CE Phase: Number of participants achieving Overall survival (OS)
Time Frame:Up to 36 months
Safety Issue:
Description:OS is defined as the time from randomization until death due to any cause.
Measure:CE Phase: Number of participants with AEs and SAEs
Time Frame:Up to 36 months
Safety Issue:
Description:AEs and SAEs will be collected.
Measure:CE Phase: Number of participants with AEs leading to discontinuation
Time Frame:Up to 36 months
Safety Issue:
Description:Number of participants with AEs leading to discontinuation will be evaluated.
Measure:CE Phase: Number of participants with dose reduction or delay
Time Frame:Up to 36 months
Safety Issue:
Description:Number of participants with dose reduction or delay will be evaluated.
Measure:CE Phase: Number of participants with abnormality in vital signs
Time Frame:Up to 36 months
Safety Issue:
Description:Vital sign measurements will include systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate.
Measure:CE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters
Time Frame:Up to 36 months
Safety Issue:
Description:Blood and urine samples will be collected to evaluate hematology, clinical chemistry and urinalysis lab parameters.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • Belantamab mafodotin
  • GSK2857916
  • GSK3174998
  • GSK3359609
  • Nirogacestat
  • Dostarlimab
  • Platform study
  • Relapsed/Refractory Multiple Myeloma

Last Updated

August 6, 2020