A study to explore the safety and clinical activity of GSK2857916 when given with pembrolizumab in study participants with relapsed/refractory multiple myeloma (DREAMM 4)

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Overview

This research study is being done to learn more about relapsed/refractory multiple myeloma, and if the study drug GSK2857916 given in combination with pembrolizumab can improve your relapsed/refractory multiple myeloma or make you feel better. 

We also would like to answer the following questions:

  • Is GSK2857916 given with pembrolizumab safe?
  • What dose of GSK2857916 given with pembrolizumab works best?
  • How well does GSK2857916 given with pembrolizumab work to treat people with relapsed/refractory multiple myeloma

Pembrolizumab, to be given with GSK2857916 in this study, is approved to treat patients with various types of cancer.  It is not approved for the treatment of the type of cancer like the kind you have, but it is being studied to see how well it works in many types of cancer.

Two studies, KEYNOTE-183 and KEYNOTE-185, looked at study participants with the same type of cancer you have, but with other study drugs combined with pembrolizumab. The other study drugs were types of drugs called immunomodulatory agents (pomalidomide [KEYNOTE-183] or lenalidomide [KEYNOTE-185]) plus dexamethasone (a type of steroid).  These drugs work by adjusting the immune response in your body.

In both studies, control groups were used to compare against the pembrolizumab combination. The control group was made up of study participants who received lenalidomide or pomalidomide plus dexamethasone, without pembrolizumab. The Food and Drug Administration (FDA) was allowed to see results obtained during those studies, and before the study officially ended. The results showed an increased risk of death for study participants in the group receiving pembrolizumab with these other study drugs. For KEYNOTE-183, the estimated risk of death was 1.6 times more than the control arm (without pembrolizumab). For KEYNOTE-185, the estimated risk of death was doubled (2 times more than the control arm).

More information is at this website:

https://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm574347.htm

If you have any questions about these studies, you can discuss them with your study doctor.

This current study will combine pembrolizumab with GSK2857916, which is not similar to the drugs combined with pembrolizumab in the studies that were stopped by the FDA.  There is a chance that by adding pembrolizumab to GSK2857916, there may be an increase in toxicity (bad effects) by combining these drugs.

The study will be conducted in two parts.

Part 1:

In Part 1, about 12 people in approximately 4 countries may be in the study. Part 1 of the study will look at how people react to and how the body uses GSK2857916 at different doses when taken with pembrolizumab.

We also want to know how the combination of the 2 study drugs affects your cancer and how the body handles the drugs when GSK2857916 and pembrolizumab are given together, and whether these two study drugs affect each other in the body. We will give study participants different doses of GSK2857916. The effects of the study drugs, both good and bad, will be studied.

Approximately 2 dose levels of GSK2857916 will be tested.  At least 3 study participants will receive GSK2857916 at each dose level before a decision is made to give the next dose level. Side effects and lab results will be reviewed to be sure that the dose is safe before making the decision about the next dose to be given.  Neither you nor the study doctor can choose which dose you will be assigned to. 

Part 2:

After the best dose of GSK2857916 is determined in Part 1, about 28 people in approximately 4 countries may enroll in Part 2 of the study. Part 2 of the study will start in different study participants than in Part 1 to test the effects of the best dose of GSK2857916 (identified in Part 1) plus pembrolizumab in a larger group of study participants with relapsed/refractory multiple myeloma. The study doctor will explain to you in which Part, Part 1 or Part 2, you will be participating.

The study drugs are planned to be given once every 3 weeks on Day 1 of each 21 day cycle.  GSK2857916 will be given at different dose levels (2.5 mg/kg or 3.4 mg/kg) as an IV infusion into a vein, followed by a 1-hour rest.  Then pembrolizumab will be given as an IV infusion of 200mg.  If you have an infusion-related reaction to GSK2857916, your dose of pembrolizumab may be delayed or skipped. If there is any need to delay or skip your dose of GSK2857916, your dose of pembrolizumab will not be administered until your next dose of GSK2857916. Your study doctor will tell you how long these infusions will last. 

You may be in the study as long as you are receiving benefit without side effects that you can’t tolerate from taking GSK2857916 plus pembrolizumab, for a maximum of 35 cycles (about 2 years).  Your participation in the study will end if you have reached the maximum 35 cycles, have disease progression (your multiple myeloma gets worse) or decide to stop participating in the study.

SparkCures ID 987
Trial Phase Phase 2
Enrollment 40 Patients
Treatments
Trial Sponsors
  • GlaxoSmithKline
NCT Identifier

NCT03848845

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.

You may be eligible to participate in this study if you:

  • Are at least 18 years old.
  • Have Relapsed or refractory multiple myeloma
  • Has undergone stem cell transplant or is considered transplant ineligible
  • Have been treated with at least three prior lines of multiple myeloma therapy including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody alone or in combination.
  • Have not received systemic anti-myeloma therapy or an investigational drug ≤ 14 days or five half-lives, whichever is shorter, preceding the first dose of study drugs
  • Have not received prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs
  • Have NOT received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another T-cell receptor and was discontinued from that treatment due to a moderate to severe immune related adverse event 

The following criteria is provided for health care professionals.

Inclusion criteria:

  • 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 (at the time consent is obtained).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Subjects must: have histologically or cytologically confirmed diagnosis of Multiple myeloma (MM), as defined by IMWG, 2014 and has undergone stem cell transplant or is considered transplant ineligible, and has been treated with at least 3 prior lines of prior anti-myeloma treatments including an immunomodulatory imide drug (IMiD) (eg. lenalidomide or pomalidomide), a proteasome inhibitor (eg. bortezomib, ixazomib or carfilzomib) and an anti-CD38 antibody alone or in combination. Line of therapy are defined by consensus panel of the International Myeloma Workshop, Has measurable disease defined as one the following: a) Serum M-protein >=0.5 grams per deciliter (g/dL) (>=5 grams per liter [g/L]). b) Urine M-protein ≥200 mg/24h. c) Serum Free light chain (FLC) assay: Involved FLC level ≥10 milligrams per deciliter (mg/dL) (≥100 milligrams per liter [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: a) transplant was > 100 days prior to study enrolment. b) no active infection(s). c) subject meets the remainder of the eligibility criteria.
  • Adequate organ system functions as defined by the laboratory assessments.
  • All prior treatment-related toxicities (defined by National Cancer Institute-Common Toxicity Criteria for Adverse Events [NCI-CTCAE], version 4.03, 2010) must be <= Grade 1 at the time of enrolment except for alopecia and Grade 2 neuropathy.
  • A female subject 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 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 120 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. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
  • Male subjects are eligible to participate if they agree to the following during the intervention period and for at least 140 days after the last dose of study intervention. Male subjects should 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 a male condom and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.

Exclusion criteria:

A subject will NOT be eligible for inclusion in this study if any of the following criteria apply:

  • Systemic anti-myeloma therapy or an investigational drug <=14 days or five half-lives, whichever is shorter, preceding the first dose of study drug
  • Plasmapheresis within 7 days prior to the first dose of study drug
  • Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs
  • Has received prior therapy with an anti-PD-1, anti-Programmed cell death Ligand 1 (PD-L1), or anti-Programmed cell death Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune related adverse event (irAE)
  • Current corneal epithelial disease except mild punctate keratopathy
  • Any major surgery within the last four weeks prior to the first dose of study therapy
  • 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, provided they fulfil criteria as per adequate organ system function mentioned under inclusion criteria.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
  • Has received prior radiotherapy within 2 weeks of start of study therapy. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (<=2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
  • History of (non-infectious) pneumonitis that required steroids, or current pneumonitis
  • Current active liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
  • 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 (RRMM). Subjects with curatively treated non-melanoma skin cancer are allowed.
  • Has known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study therapy
  • Evidence of cardiovascular risk including any of the following: a) corrected for heart rate by Fridericia's formula (QTcF) interval ≥470 msecs. b) Evidence of current clinically significant uncontrolled arrhythmias; i. including clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block. c) History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening. d) Class III or IV heart failure as defined by the New York Heart Association functional classification system. e) Uncontrolled hypertension. f) Presence of cardiac pacemaker (or defibrillator) with a predominantly ventricular paced rhythm, limiting ECG/QTcF analysis. g) Abnormal cardiac valve morphology (>=Grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2857916 or pembrolizumab, or any of the components of the study treatment.
  • Pregnant or lactating female.
  • Known 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.
  • Has received a live-virus vaccination within 30 days of planned start of study therapy.
  • Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other chronic form of immunosuppressive therapy within 7 days prior the first dose of study therapy.
  • Has known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study.
  • Has had an allogenic tissue/solid organ transplant

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

Not Currently Accepting Patients

The following is a listing of trial locations that are not currently open and accepting patients.

Medical College of Wisconsin<br />Froedtert Hospital
IU Simon Cancer Center<br />Indiana University
Levine Cancer Institute<br />Atrium Health
Mount Sinai Hospital<br />Tisch Cancer Institute
Georgia
Winship Cancer Institute of Emory University<br />
Indiana
IU Simon Cancer Center<br />Indiana University
New York
Mount Sinai Hospital<br />Tisch Cancer Institute
North Carolina
Levine Cancer Institute<br />Atrium Health
Wisconsin
Medical College of Wisconsin<br />Froedtert Hospital
International Locations

This trial has active trial locations in countries outside of the United States.

Our system currently only provides clinical trial matching services for myeloma patients in the United States.

You can view this clinical trial's international locations by visiting ClinicalTrials.gov. Please note the information provided through the government website may be inaccurate and/or out-dated.

Resources

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