MC# 19-40 - A Phase III, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Single Agent Belantamab Mafodotin Compared to Pomalidomide plus Low-dose Dexamethasone (pom/dex) in Participants with Relapsed/Refractory Multiple Myeloma (RRMM)

  • Agent(s): Belantamab Mafodotin
  • Disease Type(s): Myeloma
  • Phase(s): III
  • Drug Classification(s): Antibody Drug Conjugate
  • Molecular Target(s): BCMA

Mechanism of Action

GSK2857916 is a humanized anti-BCMA monoclonal antibody conjugated to the cytotoxic agent monomethyl auristatin-F, via non-cleavable linker.

Purpose

In this study, the sponsor and investigators want to learn:

  • About the safety and tolerability of Belantamab Mafodotin compared to pomalidomide/dexamethasone
  • How proteins that indicate the status of your disease are affected with use of Belantamab Mafodotin
  • If Belantamab Mafodotin prevents or delays disease growth compared to pomalidomide/dexamethasone
  • How fast Belantamab Mafodotin is removed from the bloodstream
  • If research tests can be used in the future to predict who will benefit from Belantamab Mafodotin
Inclusion Criteria
  • Participants must be 18 or older, at the time of signing the informed consent
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Histologically or cytologically confirmed diagnosis of MM as defined according to International Myeloma Working Group (IMWG), and:
    • Has undergone autologous stem cell transplant (SCT), or is considered transplant ineligible, and
    • Has received at least 2 prior lines of anti-myeloma treatments, including at least 2 consecutive cycles of both lenalidomide and a proteasome inhibitor (given separately or in combination), and must have documented disease progression on, or within 60 days of, completion of the last treatment as defined by IMWG
  • Has measurable disease with at least one of the following:
    • Serum M-protein ≥0.5 g/dL (≥5 g/L)
    • Urine M-protein ≥200 mg/24 hours
    • Serum free light chain (FLC) assay: Involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)
  • Participants with a history of autologous SCT are eligible for study participation provided the following eligibility criteria are met:
    • Transplant was >100 days prior to initiating study treatment
    • No active infection(s)
    • Participant meets the remainder of the eligibility criteria outlined in this protocol
  • Adequate organ system functions as defined:
    • Absolute neutrophil count (ANC) ≥1.0x109/L
    • Hemoglobin ≥8.0 g/dL
    • Platelets ≥50x109/L
    • Total bilirubin ≤1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
    • ALT ≤2.5xULN
    • Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2
    • Spot urine (albumin/creatinine ratios) ≤500 mg/g (56 mg/mmol)
    • Left ventricular ejection fraction (LVEF) (echocardiogram) Clinically asymptomatic participants with ECHO confirmed LVEF ≥25%
  • Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
    • Male Participants:
      • Male participants are eligible to participate if they agree to the following during the intervention period and until 5 months after the last dose of study intervention to allow for clearance of any altered sperm:
        • Refrain from donating sperm
        • PLUS, either:
          • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
          • Must agree to use contraception/barrier as detailed below depending on whether they are randomised to Arm 1 (belantamab mafodotin) or Arm 2 (pomalidomide/dexamethasone), even if they have undergone a successful vasectomy
        • Agree to use a male condom throughout study treatment including the 5 month follow-up period even if they have undergone a successful vasectomy and a female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year when having sexual intercourse with a pregnant woman or a woman of childbearing potential who is not currently pregnant
    • Female Participants:
      • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
        • Is not a woman of childbearing potential (WOCBP) OR
        • Is a WOCBP and agrees to abide by the following:
          • Arm 1 (belantamab mafodotin): Use a contraceptive method that is highly effective (with a failure rate of <1% per year) which includes abstinence, preferably with low user dependency during the intervention period and for 8 months after the last dose of study treatment
          • Arm 2 (pomalidomide/dexamethasone): Due to pomalidomide being a thalidomide analogue with risk for embryofetal toxicity and prescribed under a pregnancy prevention/controlled distribution program, WOCBP participants will be eligible if they commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control (one method that is highly effective), beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy, during dose interruptions and continuing for at least 4 weeks following discontinuation of pomalidomide treatment
        • Two negative pregnancy tests must be obtained prior to initiating therapy.  The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing pomalidomide therapy.
        • And agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period
        • The investigator should confirm the effectiveness of the contraceptive method(s) ahead of the first dose of study intervention
  • All prior treatment-related toxicities must be ≤Grade 1 at the time of enrollment, except for alopecia and Grade 2 peripheral neuropathy
Exclusion Criteria
  • Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes); active plasma cell leukemia at the time of screening
  • Systemic anti-myeloma therapy or use of an investigational drug within <14 days or 5 half-lives, whichever is shorter, before the first dose of study intervention
  • Prior treatment with an anti-MM monoclonal antibody within 30 days prior to receiving the first dose of study intervention
  • Prior BCMA-targeted therapy or prior pomalidomide treatment
  • Plasmapheresis within 7 days prior to the first dose of study intervention
  • Prior allogeneic stem cell transplant
    • NOTE – Participants who have undergone syngeneic transplant will be allowed only if no history of, or currently active, GvHD
  • Any major surgery within the last 4 weeks
  • Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant’s safety).  Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil criteria.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with participant’s safety, obtaining informed consent, or compliance with study procedures
  • History of (non-infectious) pneumonitis that required steroids, or current pneumonitis
  • Evidence of active mucosal or internal bleeding
  • Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis
    • NOTE: Stable chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria
  • Participants with previous or concurrent malignancies other than multiple myeloma are excluded, unless the second malignancy has been considered medically stable for at least 2 years.  The participant must not be receiving active therapy, other than hormonal therapy for this disease.
    • NOTE – Participants with curatively treated non- melanoma skin cancer are allowed without a 2-year restriction
  • Evidence of cardiovascular risk including any of the following:
    • QT interval corrected for heart rate by Fridericia’s formula (QTcF) ≥480 msec
    • Evidence of current clinically significant uncontrolled arrhythmias including clinically significant electrocardiogram (ECG) abnormalities including 2nd degree (Mobitz Type II) or 3rd degree atrioventricular block
    • History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening
    • Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
    • Uncontrolled hypertension
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin, pomalidomide, dexamethasone or any of the components of the study intervention
  • Pregnant or lactating female
  • Active infection requiring treatment
  • Known human immunodeficiency virus (HIV)
  • Presence of hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) at screening or within 3 months prior to first dose of study intervention
  • Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention
    • NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained
  • Hepatitis RNA is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing
  • Participants unable to tolerate thromboembolic prophylaxis

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/show/NCT04162210

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Re: MC# 19-40