DREAMM6

DREAMM6

To Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-drug Conjugate, GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or in Combination With Bortezomib Plus Dexamethasone (Arm B) in Subjects With Relapsed/Refractory Multiple Myeloma (RRMM)

Disease:

Multiple Myeloma

Summary:

Plasma cells are part of the immune system and are normally found in small numbers in the bone marrow. In a healthy immune system, they are responsible for producing antibodies to fight infection. Multiple myeloma, also known as myeloma, is a cancer of plasma cells. This results in excess production of abnormal antibodies, or of their component parts known as light chains, which can accumulate in the kidney, bones and bone marrow. This can result in kidney failure, fractures, high calcium levels and low blood counts which may in turn lead to fatigue, shortness of breath, bleeding and infections.
There are now many different treatment options for myeloma, but it remains incurable. This means that even though myeloma can often be treated very effectively, it will come back at some stage.
One class of therapy in development for myeloma is antibody-drug-conjugates. These consist of an antibody which binds to a specific target on cancer cells, joined to another compound which facilitates the cancer cell to internalise the molecule, and subsequently release a ‘killing’ molecule inside the cancer cell, leading to cancer cell death.
B cell maturation antigen (BCMA) is one protein that is expressed at high levels on myeloma cells. GSK2857916, the antibody-drug conjugate being investigated in this trial, targets and binds to BCMA, is internalised, and leads to myeloma cell death.
In this trial, GSK2857916 is given in combination with established myeloma treatment, - dexamethasone plus either lenalidomide or bortezemib. The treatment received alongside the trial drug is decided for each individual patient by the trial doctors.
This trial is for people with myeloma who have previously received treatment for myeloma, and the myeloma has either not responded to treatment, or has responded well but has now come back.

Eligibility:

Include, but not limited to, the following:

Inclusion Criteria:
1. 18 years or older (at the time consent is obtained).
2. Have confirmed diagnosis of Multiple Myeloma (MM) as defined by the IMWG.
3. Eastern Cooperative Oncology Group (ECOG) performance status of Arm A: 0- 1 and Arm B: 0-2.
4. Have undergone stem cell transplant (SCT), or are considered transplant ineligible.
5. 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.
6. Must have at least ONE aspect of measurable disease, as per protocol eligibility criteria
7. Participants with a history of autologous SCT, are eligible for study participation provided eligibility criteria as per protocol are met
8. All prior treatment-related toxicities are Grades =/< as defined in the protocol 9. Adequate organ system functions as defined by the laboratory assessments. 10. Female participants adhere to contraception and breastfeeding regulations as defined in protocol 11. Male participants adhere to contraception and sperm donation regulations as defined in protocol Exclusion Criteria: 1. Systemic anti-myeloma therapy (including systemic steroids) within 14 days, or plasmapheresis within 7 days prior to the first dose of study drug. 2. Use of an investigational drug within 14 days or five half-lives (whichever is longer) preceding the first dose of study drug. 3. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs. 4. 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. 5. Any major surgery within the last four weeks. 6. Presence of active renal condition as defined in protocol 7. Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions as defined in protocol 8. Current active liver or biliary disease as defined in protocol 9. Participants with invasive malignancies, other than multiple myeloma, which have not been considered medically stable for at least 2 years. *See protocol for more info 10. Evidence of cardiovascular risk as defined in protocol 11. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to GSK2857916, or any of the components of the study treatment. 12. Pregnant or lactating female. 13. Active infection requiring treatment. 14. Known HIV infection. 15. 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). 16. Current corneal disease except for mild punctuate keratopathy. 17. 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. *See protocol for more info 18. Current corneal disease except for mild punctuate keratopathy. 19. Additional Exclusion Criteria for participants Assigned to Treatment arm A and Treatment arm B Please refer to protocol Eligibility Criteria: https://clinicaltrials.gov/ct2/show/NCT03544281

Contact person:

Lewis Edwards (Clinical trials Coordinator, Linear Clinical Research)
Email ledwards@linear.org.au
Phone


Email
Phone

Principal Investigator:

Dr Bradley Augustson

Sponsor:

Glaxosmithkleine

Phase:

I/II

Protocol Number:

LO180303

Trial Registration Number:

NCT03544281

Clinical Trials.gov

ANZ Clinical Trial Registry