A Phase I/II Study to Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-Drug Conjugate GSK2857916 Administered in Combination with Lenalidomide Plus Dexamethasone (Arm A), or Bortezomib Plus Dexamethasone (Arm B) in Participants with Relapsed / Refractory Multiple Myeloma (DREAMM 6)

Verified

Overview

The purpose of this study is to evaluate the safety of the study drug, GSK2857916, at different doses and how well it works to treat people with multiple myeloma when taken together with Lenalidomide Plus Dexamethasone (Treatment Arm A), or Bortezomib Plus Dexamethasone (Treatment Arm B).

GSK2857916 is not yet approved by regulatory authorities such as the United States’ Food and Drug Administration (FDA), Health Canada and European Medicine agencies, for doctors to treat patients with relapsed or refractory multiple myeloma. Lenalidomide Plus Dexamethasone (Len/Dex) or Bortezomib Plus Dexamethasone (Bor/Dex) are approved drugs and are used as Standard of Care to treat patients with multiple myeloma. However, Len/dex or Bor/Dex are not yet approved to be used in combination with GSK2857916 in multiple myeloma. It is therefore being studied to see how well GSK2857916 works in combination with Len/Dex or Bor/Dex in multiple myeloma.

The study will be conducted in 2 parts (Part 1 and Part 2); you will only have the opportunity to participate in one part of the study.

Part 1 of the study is called “Dose Escalation” in which we will give people different amounts of GSK2857916 in combination with Len/Dex (Treatment A), or Bor/Dex (Treatment B). The main goal of Part 1 of the study is to determine the highest dose of GSK2857916 in combination with Len/Dex or Bor/Dex that can be given safely and with the least harmful side effects. We also want to know how the body handles the drugs when GSK2857916 and Len/Dex or Bor/Dex are given together and what effect GSK2857916 and Len/Dex or Bor/Dex have on your cancer growth rate.

Part 2 of the study is called “Cohort Expansion”. Part 2 of the study will start in a separate group of participants when Part 1 is completed. The main goal of Part 2 will be to test the effects of the optimal dose of GSK2857916 identified in Part 1 given in combination with Len/Dex or Bor/Dex in a larger group of participants with relapsed or refractory multiple myeloma.

Your treating physician, in consultation with you, will decide whether Treatment A (GSK2857916 + Lenalidomide + Dexamethasone) or Treatment B (GSK2857916 + Bortezomib + Dexamethasone) will work best for you.

GSK2857916 plus Lenalidomide Plus Dexamethasone (Treatment A)

Part 1: Dose Escalation

If you participate in the dose escalation part and are assigned to Treatment A, you will receive GSK2857916 along with Lenalidomide and Dexamethasone on a 28day cycle as follows:

  • GSK2857916 will be given in the clinic on Day 1 of each 28-day cycle as a 30‑min infusion, followed by a 1-hr rest period.
  • Lenalidomide will be given as 25 mg by mouth daily on days 1- 21 of each 28-day cycle. The dose of Lenalidomide will be reduced to 10 mg daily in participants who have poor kidney function.
  • Dexamethasone will be given as 40 mg by mouth weekly on Day 1, 8, 15 and 22 of each cycle. Both Lenalidomide and Dexamethasone can be taken at home. On days where only Lenalidomide and dexamethasone are taken at home, they should be taken in the morning approximately at the same time each day.

Two dose levels (2.5mg/kg & 3.4mg/kg) of GSK2857916 are planned to be tested in combination with the fixed doses of the Standard of Care treatment (Len/Dex). Side effects and lab results will be reviewed from at least 3 participants to be sure that the GSK2857916 dose is safe before a decision is made to move on to the next dose level.

Part 2: Cohort Expansion

Part 2 of the study will start after Part 1 of the study has ended. If you participate in the cohort expansion part and are assigned to Treatment A, you will receive GSK2857916 along with Lenalidomide and Dexamethasone on a 28day cycle as follows: 

  • GSK2857916 will be given in the clinic at dose, identified safe and effective in part one, on Day 1 of each 28-day cycle as a 30‑min infusion, followed by a 1-hr rest period.
  • Lenalidomide will be given as 25 mg by mouth daily on days 1- 21 of each 28-day cycle. The dose of Lenalidomide will be reduced to 10 mg daily in participants who have poor kidney function.
  • Dexamethasone will be given as 40 mg by mouth weekly on Day 1, 8, 15 and 22 of each cycle. Both Lenalidomide and Dexamethasone can be taken at home. On days where only Lenalidomide and dexamethasone are taken at home, they should be taken in the morning approximately at the same time each day.

Participants who experience serious side effects may have their dose delayed and/or lowered. In case, if any participant meets stopping criteria for Len/Dex treatment, the participant will still be allowed to continue the study with GSK2857916 only. However, in case the participant meets stopping criteria for GSK2857916, then that participant will be removed from the study. 

There may be care and treatment options available to you after the study is over. Your study doctor will talk with you about your treatment choices. 

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

  • After your screening period you will need to visit the clinic every 4 weeks to receive the study drug as long as you are not experiencing harmful side effects and are receiving benefit from treatment with GSK2857916 and Len/Dex.
  • During the first 4 doses of GSK2857916, you will also need to visit an ophthalmologist (eye doctor) every 4 weeks for eye examinations. These visits may continue at the same frequency after the first 4 doses if you have certain side effects in your eyes; but if you don’t have side effects in your eyes, these exams can be reduced to once every 12 weeks. 
  • Most visits will require about 4-8 hours of your time.
  • In your case, if the study drug was stopped for any reason, depending on why you stopped the study drug, you may continue to have visits every 4 weeks so that we can follow your disease or your doctor’s office will call every 3 months to check on your health. The study will end approximately by winter of 2022.

During the study

You will need to come to our clinic for scheduled visits every 4weeks for treatment, blood and urine tests, CT/MRI/PET or X-rays (if required), bone marrow tests (if required) and questionnaires. Up to a total of about 13.4 teaspoons of blood (67mL) will be collected at some visits.

End of Treatment Visit

When you have finished taking the study drug, you will need to come to the clinic for an End of Treatment visit about 30 days after your last dose, or prior to any new treatment for your multiple myeloma (whichever comes first). 

Progression-Free Survival (PFS) Follow-up Visits

If you have stopped receiving study treatment other than worsening disease, then you will need to come to the clinic every 4 weeks for a visit called Progression-Free Survival (PFS) Follow-up. This follow-up will continue till the time your disease gets worse or you start new treatment for your multiple myeloma or you withdraw your consent (whichever comes first).

Overall Survival Follow-up contacts 

Once you have come off treatment completely, you will be contacted by your doctor or study staff every 3 months by telephone to see how you are doing. This is to find out if the drug has helped prolong your life. 

GSK2857916 plus Bortezomib Plus Dexamethasone (Treatment B)

Part 1: Dose Escalation 

If you participate in the dose escalation part and are assigned to Treatment B, you will receive GSK2857916 along with Bortezomib and Dexamethasone on a 21day cycle as follows:

  • GSK2857916 will be given in the clinic on Day 1 of each 21-day cycle as a 30‑min infusion, followed by a 1-hr rest period.
  • Bortezomib will be given as 1.3 mg/m2 subcutaneous or Intravenously (depending on your choice and hospital practice) 1 hour after GSK2857916 administration on Days 1, 4, 8, and 11 of every 21-day cycle for a total of 8 cycles.
  • Dexamethasone will be given as 20 mg by mouth or intravenously on Days 1, 2, 4, 5, 8, 9, 11, and 12 of every 21-day cycle for a total of 8 cycles.
  • Dexamethasone can be taken at home approximately at the same time each day.

Two dose levels (2.5mg/kg & 3.4mg/kg) of GSK2857916 are planned to be tested in combination with the fixed doses of the Standard of Care treatment (Bor/Dex). Side effects and lab results will be reviewed from at least 3 participants to be sure that the GSK2857916 dose is safe before a decision is made to move on to the next dose level.

Part 2: Cohort Expansion

  • Part 2 of the study will start after Part 1 of the study has ended. If you participate in the cohort expansion part and are assigned to Treatment B, you will receive GSK2857916 along with Bortezomib and Dexamethasone on a 21day cycle as follows:
  • GSK2857916 will be given in the clinic at dose, identified safe and effective in part one, on Day 1 of each 21-day cycle as a 30‑min infusion, followed by a 1-hr rest period.
  • Bortezomib will be given as 1.3 mg/m2 subcutaneous or Intravenously (depending on your choice and hospital practice) 1 hour after GSK2857916 administration on Days 1, 4, 8, and 11 of every 21-day cycle for a total of 8 cycles.
  • Dexamethasone will be given as 20 mg by mouth or intravenously on Days 1, 2, 4, 5, 8, 9, 11, and 12 of every 21-day cycle for a total of 8 cycles.
  • Dexamethasone can be taken at home approximately at the same time each day.

Participants who experience serious side effects may have their dose delayed and/or lowered. In case, if any participant meets stopping criteria for Bor/Dex treatment, the participant will still be allowed to continue the study with GSK2857916 only. However, in case the participant meets stopping criteria for GSK2857916, then that participant will be removed from the study.

There may be care and treatment options available to you after the study is over. Your study doctor will talk with you about your treatment choices.

What do you 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 the study drug as long as you are not experiencing harmful side effects and are receiving benefit from treatment with GSK2857916 and Bor/Dex. 
  • During the first 4 doses of GSK2857916, you will also need to visit an ophthalmologist (eye doctor) every 3 weeks for eye examinations. These visits may continue at the same frequency after the first 4 doses if you have certain side effects in your eyes; but if you don’t have side effects in your eyes, these exams can be reduced to once every 12 weeks. 
  • Most visits will require about 4-8 hours of your time.
  • In your case, if the study drug was stopped for any reason, depending on why you stopped the study drug you may continue to have visits every 3 weeks so that we can follow your disease or your doctor’s office will call every 3 months to check on your health. The study will end approximately by winter of 2022.

During the study

You will need to come to our clinic for scheduled visits every 3 weeks for treatment, blood and urine tests, CT/MRI or X-rays (if required), bone marrow tests (if required) and questionnaires. Additionally, you will also need to come on Day 4, 8 and 11 of up-to 8 Bortezomib cycles during which some assessments (vitals, hematology, chemistry) may be repeated prior to Bortezomib infusion. Up to a total of about 18.2 teaspoons of blood (91mL) will be collected at some visits.

End of Treatment Visit

When you have finished taking the study drug, you will need to come to the clinic for an End of Treatment visit about 30 days after your last dose, or prior to any new treatment for your multiple myeloma (whichever comes first).

Progression-Free Survival (PFS) Follow-up Visits

If you have stopped receiving study treatment other than worsening disease, then you will need to come to the clinic every 3 weeks for a visit called Progression-Free Survival (PFS) Follow-up. This follow-up will continue till the time your disease gets worse or you start new treatment for your multiple myeloma or you withdraw your consent (whichever comes first).

Overall Survival Follow-up Contacts 

Once you have come off treatment completely, you will be contacted by your doctor or study staff every 3 months by telephone to see how you are doing. This is to find out if the drug has helped prolong your life. 

Do you have to stay in the study?

  • No.  Your participation in the study is voluntary and you can leave the study at any time without giving a reason.  Tell the study staff if you want to stop being in the study.  Your decision will not affect your medical care now or in the future.  It will not affect other benefits you receive outside of the study.
  • The study doctor will tell you as soon as possible if there is any new information that might change your decision to stay in the study.
SparkCures ID 977
Trial Phase Phase 1/2
Enrollment 90 Patients
Treatments
Trial Sponsors
  • GlaxoSmithKline
NCT Identifier

NCT03544281

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:

  • Have confirmed diagnosis of Multiple Myeloma
  • Male or female, 18 years or older.
  • Have undergone stem cell transplant (STC), or are considered transplant ineligible.
  • Have been previously treated with at least 1 prior line of MM therapy, and must have documented disease progression during or after their most recent therapy.
  • Must have at least ONE aspect of measurable disease, defined as one the following:
      • Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or
      • Urine M-protein excretion ≥200 mg/24h, or
      • 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).
  • Participants with a history of autologous stem cell transplant (SCT) are eligible for study participation provided the following eligibility criteria are met:
      • Autologous SCT was >100 days prior to study enrollment
  • Adequate organ system functions
  • Must not have received a prior allogeneic stem cell transplant (ASCT)
  • Must not have prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs.

The following criteria is provided for health care professionals.

Inclusion Criteria:

  • Capable of giving signed informed consent.
  • Male or female, 18 years or older (at the time consent is obtained).
  • Have confirmed diagnosis of Multiple Myeloma as defined by the IMWG.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Have undergone stem cell transplant (SCT), or are considered transplant ineligible.
  • Have been previously treated with at least 1 prior line of MM therapy, and must have documented disease progression during or after their most recent therapy according to the IMWG criteria.
  • Must have at least ONE aspect of measurable disease, defined as one the following: Urine M-protein excretion >=200 milligram (mg)/24 hours, or; Serum M-protein concentration >=0.5 gram (g)/deciliter (dL) (>=5.0 g/Liter), or; 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).
  • Subjects with a history of autologous SCT, are eligible for study participation provided the following eligibility criteria are met: Autologous SCT was >100 days prior to study enrollment; No active bacterial, viral, or fungal infection(s) present; Subject meets the remainder of the eligibility criteria.
  • 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 enrollment, except for alopecia. Subjects with Grade 2 neuropathy can be enrolled into Len/Dex treatment arm, but not into Bor/Dex treatment arm.
  • Adequate organ system functions as defined by the laboratory assessments.
  • The contraception's used by female subject's be consistent with local regulations, regarding methods of contraception for those participating in clinical studies. 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 child bearing 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. WOCBP must have 2 negative highly sensitive serum pregnancy tests, as required by local regulations (first within 14 days of Cycle 1 Day 1 and the second one within 72 hours of dosing on Cycle1 Day1) and agree to use effective contraception during the study and for 120 days after the last dose of study medication; 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 subject's using contraception should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Males are eligible to participate if they as detailed below: 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 WOCBP who is not currently pregnant.

Exclusion Criteria:

  • Systemic anti-myeloma therapy (including systemic steroids) within 14 days, or plasmapheresis within 7 days prior to the first dose of study drug.
  • Use of an investigational drug within 14 days or five half-lives (whichever is longer) 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 allogenic stem cell transplant.
  • 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, provided they fulfill 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.
  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease per investigator's assessment).
  • Subjects with previous or concurrent malignancies are allowed only if the second tumor is not contributing to the subject's illness. The subject must not be receiving active therapy, other than hormonal therapy for this disease and the disease must be considered medically stable for at least 2 years.
  • Evidence of cardiovascular risk including any of the following:
    • Corrected QT (QTc) interval >=470 millisecond (msec); Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities including 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; Uncontrolled hypertension.
  • Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to GSK2857916, or any of the components of the study treatment.
  • Pregnant or lactating female.
  • Active infection requiring treatment.
  • Known 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).
  • Current corneal disease except for mild punctuate keratopathy.
  • 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 treatment. NOTE: 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.
  • Current corneal disease except for mild punctuate keratopathy.
  • Additional Exclusion Criteria for subjects Assigned to Treatment A: Subjects unable to tolerate antithrombotic prophylaxis must be excluded; Discontinuation of prior treatment with lenalidomide due to intolerable AEs.
  • Additional Exclusion Criteria for Subjects Assigned to Treatment B: Unacceptable AEs from previous bortezomib treatment; Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain from previous bortezomib treatment; Intolerance or contraindications to anti-viral prophylaxis.

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.

Winship Cancer Institute of Emory University<br />
John Theurer Cancer Center<br />Hackensack Meridian Health
IU Simon Cancer Center<br />Indiana University
Mayo Clinic (Rochester)
Mayo Clinic (Rochester)

Rochester, MN

Montefiore Medical Center
Montefiore Medical Center

Bronx, NY

Memorial Sloan Kettering Cancer Center<br />Memorial Hospital
Greenville Memorial Hospital<br />Greenville Health System
Greenville Memorial Hospital
Greenville Health System

Greenville, SC

Alabama
Georgia
Winship Cancer Institute of Emory University<br />
Indiana
IU Simon Cancer Center<br />Indiana University
Minnesota
Mayo Clinic (Rochester)
Mayo Clinic (Rochester)

Rochester, MN

Missouri
Siteman Cancer Center<br />Washington University Medical Campus
New Jersey
John Theurer Cancer Center<br />Hackensack Meridian Health
New York
Montefiore Medical Center
Montefiore Medical Center

Bronx, NY

Memorial Sloan Kettering Cancer Center<br />Memorial Hospital
South Carolina
Greenville Memorial Hospital<br />Greenville Health System
Greenville Memorial Hospital
Greenville Health System

Greenville, SC

Texas
Baylor Charles A. Sammons Cancer Center<br />Baylor Scott & White Health
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

GSK Compassionate Use (Expanded Access) Request Portal

GSK recognises that there may be circumstances when it is appropriate for Healthcare Professionals to give their patients Investigational medicines to treat life threatening or seriously debilitating diseases/conditions where no satisfactory alternatives exist.

SparkCures Verified

SparkCures is working closely with GlaxoSmithKline to provide the most up-to-date information on this clinical trial. Use the button above to add this trial to your list of favorites.

Learn more about how we work with trial sponsors