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 SoC combinations such as Lenalidomide Plus Dexamethasone (Arm A), or Bortezomib Plus Dexamethasone (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 SOC 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 (Arm A)or Bor/Dex (Arm B) 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 on different dosing schedules in combination with Len/Dex (Arm A), or Bor/Dex (Arm B). The main goal of Part 1 of the study is to determine the highest dose and best dose schedule 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.

Part 2 of the study is called “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 doses and dosing schedules of GSK2857916 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 Arm A (GSK2857916 + Lenalidomide + Dexamethasone) or Arm B (GSK2857916 + Bortezomib + Dexamethasone) will work best for you.

GSK2857916 plus Lenalidomide Plus Dexamethasone (ARM 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 to 60 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.

Three dose levels (1.9 mg/kg, 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 to 60 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 20.6 teaspoons of blood (103mL) 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 for 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, or end of the study (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 (ARM 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 to 60 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 ARM 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 to 60 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 28.2 teaspoons of blood (141mL) 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 for 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 , or end of the study (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 123 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 (MM) as defined by the IMWG.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 for Arm A and 0 to 2 for Arm B.
  • 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).
  • Participants 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; Participant 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. Participants 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 participant's be consistent with local regulations, regarding methods of contraception for those participating in clinical studies. 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 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 24 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; Additional requirements for pregnancy testing during and after study intervention (i.e., REMS program for WOCBP taking lenalidomide).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 participant's using contraception should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Male participants must agree to refrain from donating sperm and 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 from the time of first dose of study until 140 days after the last dose of study treatment to allow for clearance of any altered sperm: OR 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. If the female partner of the male participant is pregnant at the time of enrollment, or becomes pregnant during the trial, the male participant must agree to remain abstinent (if it is consistent with their preferred and usual lifestyle) or use a male condom. Additional criteria WOCBP participants in Arm A: Due to lenalidomide being a thalidomide analogue with risk for embryofetal toxicity and prescribed under a restricted distribution program called the REVLIMID (Lenalidomide) REMS 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, beginning 4 weeks prior to initiating treatment with lenalidomide, during therapy, during dose interruptions and continuing for 120 days following discontinuation of treatment.

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. Note: participants who have undergone syngeneic transplant will be allowed only if they have no history and no currently active, graft versus host disease (GvHD) - 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 participant's safety). Participants 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 participant'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).
  • Participants with invasive 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: a. Corrected QT (QTc) interval >=480 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 3 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: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid (RNA) test is obtained.
  • Current corneal disease except for mild punctuate keratopathy.
  • Additional Exclusion Criteria for participants Assigned to Treatment A: Participants unable to tolerate antithrombotic prophylaxis must be excluded; Discontinuation of prior treatment with lenalidomide due to intolerable AEs.
  • Additional Exclusion Criteria for Participants 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.

Cancer Treatment Centers of America Western Regional Medical Center
Cancer Treatment Centers of America Western Regional Medical Center

Goodyear, AZ

IU Simon Cancer Center Indiana University
CHI Health Saint Francis Medical Center
CHI Health Saint Francis Medical Center

Grand Island, NE

Montefiore Medical Center
Montefiore Medical Center

Bronx, NY

Prisma Health Greenville Memorial Hospital
Prisma Health Greenville Memorial Hospital

Greenville, SC

Not Currently Accepting Patients

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

North Shore Hematology Oncology Associates, P.C
North Shore Hematology Oncology Associates, P.C

East Setauket, NY

Mary Crowley Cancer Research Centers
Mary Crowley Cancer Research Centers

Dallas, TX

Arizona
Cancer Treatment Centers of America Western Regional Medical Center
Cancer Treatment Centers of America Western Regional Medical Center

Goodyear, AZ

Georgia
Winship Cancer Institute of Emory University
Indiana
IU Simon Cancer Center Indiana University
Missouri
Siteman Cancer Center Washington University Medical Campus
Nebraska
CHI Health Saint Francis Medical Center
CHI Health Saint Francis Medical Center

Grand Island, NE

New Jersey
John Theurer Cancer Center Hackensack Meridian Health
New York
Montefiore Medical Center
Montefiore Medical Center

Bronx, NY

North Shore Hematology Oncology Associates, P.C
North Shore Hematology Oncology Associates, P.C

East Setauket, NY

South Carolina
Prisma Health Greenville Memorial Hospital
Prisma Health Greenville Memorial Hospital

Greenville, SC

Texas
Baylor Charles A. Sammons Cancer Center Baylor Scott & White Health
Mary Crowley Cancer Research Centers
Mary Crowley Cancer Research Centers

Dallas, TX

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 be aware that the government website may include information that is inaccurate and/or out-of-date.

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.

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