A Study to Investigate the Efficacy and Safety of Two Doses of GSK2857916 in Subjects With Multiple Myeloma Who Have Failed Prior Treatment With an Anti-CD38 Antibody

  • Interventional
  • Recruiting
  • NCT03525678
Eligibility Details Visit Clinicaltrials.gov

A Phase II, Open Label, Randomized, Two-Arm Study to Investigate the Efficacy and Safety of Two Doses of the Antibody Drug Conjugate GSK2857916 in Participants With Multiple Myeloma Who Had 3 or More Prior Lines of Treatment, Are Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed an Anti-CD38 Antibody (DREAMM 2)

Multiple myeloma (MM) is an incurable malignancy and accounts for 1 percentage of all cancers and for 10% of all hematologic malignancies. Subjects with relapsed/refractory multiple myeloma (RRMM) will be included in this study, to evaluate the efficacy and safety of GSK2857916 monotherapy. Subjects will be treated with GSK2857916 monotherapy until disease progression or unacceptable toxicity and will be followed for Progression Free Survival (PFS) and Overall survival (OS). The subjects will be randomized to receive either frozen GSK2857916 at the dose of 2.5 milligram per kilogram (mg/kg) or 3.4 mg/kg Intravenous (IV). There will be an independent cohort of subjects who will receive a lyophilized configuration of GSK2857916. Approximately 155 subjects will be enrolled in the study of which 130 subjects will be enrolled to receive frozen GSK2857916 and 25 subjects will be enrolled in the independent lyophilized drug product cohort. The subjects who discontinued from the study other than Progressive disease (PD), disease evaluation will continue to be performed at 3-week intervals until confirmed PD, death, start of a new anticancer treatment, withdrawal of consent, or end of the study whichever occurs first.

Gender
All

Age Group
18 Years and up

Accepting Healthy Volunteers?
No

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.

At a Glance

National Government IDNCT03525678

IRB#IRB18-0545

Lead SponsorGlaxoSmithKline

Lead PhysicianAndrzej Jakubowiak

Collaborator(s)N/A

EligibilityAll
18 Years and up
Recruiting