Open-label, randomized study of two doses of GSK2857916 in participants with relapsed / refractory multiple myeloma who have failed prior treatment of an anti-CD38 antibody and are refractory to an immunomodulatory agent and a proteasome inhibitor

Overview

This research study is being done to learn more about multiple myeloma and if the study drug, GSK2857916, can improve multiple myeloma in patients who have already failed other treatments. We also would like to answer the following questions:

  • Is GSK2857916 safe?
  • How well does GSK2857916 work to treat people with relapsed/refractory multiple myeloma?

Some parts of this study are research which means they have not been tested yet.

  • The research parts of the study are: 
    • Which dose of GSK2857916 has fewer side effects and if the disease is controlled.
    • Optional tumor biopsy if you reach disease progression. This can be from a bone marrow sample or from a tumor that is outside of your bone.
    • Optional genetic research from a blood sample

Please note that GSK2857916 is not yet approved for use in people with multiple myeloma.

How does the study work? (Patient Friendly Expectations / Informed Consent Overview)

  • You are being asked to take part in this study because you have been diagnosed with multiple myeloma. This study will include about 155 patients receiving 2 different doses of GSK2857916 at approximately 68 sites globally and will last for about 2 years.
  • This study will compare two different doses of GSK2857916 and how safe they are and how they control the disease. The effects of the drug, both good and bad, will be studied.
  • All patients in this study will receive GSK2857916 at one of the 2 different doses. You will have an equal chance of being assigned to either dosing group. A computer program will put you into a dosing group by chance.

What do I need to do and know about being in the study?

  • After your screening period, you will need to visit the clinic every 3 weeks to receive study drug as long as you are not having harmful side effects and are getting benefit from treatment with GSK2857916.
  • For the first 4 cycles of study drug you will also need to visit an eye doctor every 3 weeks for eye examinations. These may need to continue at the same frequency after the first 4 cycles if you have certain visual side effects in your eyes; but if you don’t have these side effects, the exams can be reduced to every 3 months.
  • Most clinic visits will require about 4-8 hours of your time. The eye doctor visits will last about 30 minutes to an hour (not including waiting time).

How will the study treatment be administered? Am I guaranteed to receive study drug?

Yes. You will receive GSK2857916 in a vein over 30 minutes once every 3 weeks on Day 1 of each 21-day cycle.

SparkCures ID 953
Trial Phase Phase 2
Enrollment 155 Patients
Treatments
Trial Sponsors
  • GlaxoSmithKline
NCT Identifier

NCT03525678

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

Inclusion Criteria:

  • Subjects provide signed written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Male or female, 18 years or older.
  • Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Histologically or cytologically confirmed diagnosis of MM as defined according to International Myeloma Working Group (IMWG). The subject has undergone stem cell transplant or is considered transplant ineligible and has failed at least 3 prior lines of anti-myeloma treatments, including an anti-CD38 antibody (example [e.g.], daratumumab) alone or in combination, and is refractory to an Immunomodulatory drugs (IMiD) (that is [i.e.], lenalidomide or pomalidomide), and to a proteasome inhibitor (i.e., bortezomib, ixazomib or carfilzomib).
  • The subject has measurable disease with at least one of the following: Serum M-protein >=0.5 gram per deciliter (g/dL) (>=5 gram per Liter [g/L]); Urine M-protein >=200 milligram per 24 hours (mg/24h); Serum Free light chain (FLC) assay: Involved FLC level >=10 mg/dL (>=100 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65).
  • Subjects with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: transplant was >100 days prior to study enrolment; no active infection(s); subjects meets the remainder of the eligibility criteria outlined in this protocol.
  • Subjects with adequate organ system functions as defined follows: Absolute neutrophil count (ANC) >=1.0 X 10^9/L; Hemoglobin >=8.0 g/dL; Platelets>= 50 X 10^9/L; Total bilirubin <=1.5X Upper limit of normal (ULN). Isolated bilirubin >=1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent); Alanine aminotransferase (ALT) <=2.5X ULN; Estimated glomerular filtration rate (eGFR) >=30 milliliter per minute per 1.73 meter square (mL/min/m^2); Spot urine (albumin/creatinine ratios [spot urine]) < 500 milligram per gram (mg/g) (56 mg per millimoles [mg/mmol]); Left ventricular ejection fraction (LVEF) >= 45 percent.
  • Female subjects: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female subject is eligible to participate if she is not pregnant or breastfeeding, and not a woman of childbearing potential (WOCBP) or is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, during the intervention period and for at least 80 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention.
  • Male subjects are eligible to participate if they agree to the following during the intervention period and for at least 140 days: Refrain from donating sperm; Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; Agree to use a male condom and female partner to use an additional highly effective contraceptive method with a failure rate of <1 percent per year as when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
  • All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03, must be <=Grade 1 at the time of enrolment except for alopecia and Grade 2 peripheral neuropathy.
  • For France only: A subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

  • Systemic anti-myeloma therapy within <14 days, or plasmapheresis within 7 days prior to the first dose of study drug.
  • Symptomatic amyloidosis, active 'polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes' (POEMS) syndrome, active plasma cell leukemia at the time of screening.
  • Prior allogeneic stem cell transplant.
  • Current corneal epithelial disease except mild punctate keratopathy.
  • Use of an investigational drug within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs. Prior BCMA targeted therapy.
  • Evidence of active mucosal or internal bleeding.
  • Any major surgery within the last four weeks.
  • Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect subject's safety). Subjects with isolated proteinuria resulting from MM are eligible.
  • 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 to the study procedures.
  • Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if subject otherwise meets entry criteria.
  • Malignancies other than disease under study are excluded, except for any other malignancy from which the subject has been disease-free for more than 2 years and, in the opinion of the principal investigators and GSK Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy (MM).
  • Evidence of cardiovascular risk including any of the following: Corrected QT interval Fridericia (QTcF) interval >=470 milliseconds (msecs); Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block; History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening; Class III or IV heart failure as defined by the New York Heart Association functional classification system (NYHA); Uncontrolled hypertension.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2857916, or any of the components of the study treatment.
  • Pregnant or lactating female.
  • Active infection requiring antibiotic, antiviral, or antifungal treatment.
  • Known Human Immunodeficiency Virus (HIV) infection.
  • 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 treatment.
  • Positive hepatitis C antibody test result or positive hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.

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