Multiple Myeloma
Conditions
Keywords
Belantamab mafodotin, GSK2857916, GSK3174998, Feladilimab, Nirogacestat, Dostarlimab, Isatuximab, Lenalidomide, Dexamethasone, Pomalidomide, Platform study, Relapsed/Refractory Multiple Myeloma
Brief summary
B-cell maturation antigen (BCMA) is a target present on tumor cells in participants with multiple myeloma. Belantamab mafodotin (GSK2857916); is an antibody-drug conjugate (ADC) containing humanized anti-BCMA monoclonal antibody (mAb). This is a phase I/II, randomized, open-label, platform study designed to evaluate the effects of belantamab mafodotin in combination with other anti-cancer drugs in participants with relapsed/refractory multiple myeloma. The Platform design incorporates a single master protocol, where multiple treatment combinations, as sub-studies, will be evaluated simultaneously.
Interventions
DRUGBelantamab mafodotin
Belantamab mafodotin will be administered.
DRUGGSK3174998
GSK3174998 will be administered.
DRUGFeladilimab
feladilimab will be administered.
DRUGNirogacestat
Nirogacestat will be administered.
DRUGDostarlimab
Dostarlimab will be administered.
DRUGIsatuximab
Isatuximab will be administered.
DRUGLenalidomide
Lenalidomide will be administered.
DRUGDexamethasone
Dexamethasone will be administered.
DRUGPomalidomide
Pomalidomide will be administered.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
There will be a dose exploration (DE) phase which will evaluate the safety and tolerability profile of belantamab mafodotin when administered in combination with other anti-cancer treatments. A recommended Phase 2 dose (RP2D) for each combination treatment will be identified based on the safety and preliminary efficacy in DE. This will be followed by a cohort expansion (CE) phase which will evaluate the clinical activity of the combination treatment in comparison to belantamab mafodotin monotherapy in additional participants.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participant must be 18 years of age inclusive or older, at the time of signing the informed consent. * Participants must have histologically or cytologically confirmed diagnosis of Multiple Myeloma (MM), as defined by the IMWG. * Participants having at least 3 prior lines of prior anti-myeloma treatments including an immunomodulating agent (IMID) a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody. * Participants with a history of autologous stem cell transplant are eligible for study participation when, transplant was \>100 days prior to study enrolment and with no active infection(s). * Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, unless ECOG less than equal to (\<=)2 is due solely to skeletal complications and/or skeletal pain due to MM. * Participants with measurable disease defined as at least one of the following: Serum M-protein greater than equal to (\>=)0.5 gram per deciliter (\>=5 gram per liter) or Urine M-protein \>=200 mg per 24 hours or Serum free light chain (FLC) assay: Involved FLC level \>=10 mg per deciliter (\>=100 mg per Liter) and an abnormal serum FLC ratio (\<0.26 or \>1.65). * Participants who have tested positive for Hepatitis B core antibody (HBcAb) can be enrolled if the following criteria are met: Serology result HBcAb+, Hepatitis B surface antigen (HBsAg)-; HBV DNA undetectable during screening. * Participants who are currently receiving physiological doses oral steroids (\<10 mg/day), inhaled steroids or ophthalmalogical steroids. Inclusion Criteria Specific to Sub-study 6 and7: * Participants with contraception requirements specific to Sub-study 6 and 7 respectively. * Participants with platelets value for Adequate Organ System Function is ≥75 × 10\^9/L.
Exclusion criteria
* Participants with current corneal epithelial disease except mild punctate keratopathy. * Participants with evidence of cardiovascular risk * Participants with known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin or any of the components of the study treatment. History of severe hypersensitivity to other mAb. * Participants with active infection requiring antibiotic, antiviral, or antifungal treatment. * Participants with other monoclonal antibodies within 30 days or systemic anti-myeloma therapy within \<14 days. * Participants with prior radiotherapy within 2 weeks of start of study therapy. * Participants with prior allogeneic transplant are prohibited. * Participants who have received prior Chimeric Antigen T cell therapy (CAR-T) therapy with lymphodepletion with chemotherapy within 3 months of screening. * Participants with any major surgery (other than bone-stabilizing surgery) within the last 30 days. * Participants with prior treatment with an investigational agent within 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is shorter. * Participants with \>=grade 3 toxicity considered related to prior check-point inhibitors and that led to treatment discontinuation. * Participants who have received transfusion of blood products within 2 weeks before the first dose of study drug. * Participants must not receive live attenuated vaccines within 30 days prior to first dose of study treatment or whilst receiving belantamab mafodotin +- partner agent in any sub-study arm of the platform trial and for at least 70 days following last study treatment. * Participants with 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. * Participants with Known HIV infection, unless the participant can meet all criteria: a) established anti-retroviral therapy for at least 4 weeks and HIV viral load\<400 copies/mL b) CD4+ T-cell (CD4+) counts \>= 350 cells/microliter (µL) c) No history of AIDS-defining opportunistic infections within the last 12 months in which case the participant would be eligible for CE Phase only. For patients receiving nirogacestat, HIV drugs that are strong CYP3A4 inhibitors are prohibited. HIV drugs that are moderate CYP3A4 inhibitors, while permitted, should be co-administered with caution and must be accompanied by nirogacestat dose modifications. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Randomized Across Sub-studies | Day 1 | Number of Participants who passed screening and were randomized across sub studies are presented. |
Countries
Brazil, Canada, France, Germany, Greece, Mexico, Netherlands, Norway, Poland, South Korea, Spain, Sweden, United States
Contacts
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Participant flow
Recruitment details
This master record includes data of screened participants for its sub-studies, 208887 Substudy 1 (NCT06160609), Substudy 2 (NCT07217119), Substudy 3 (NCT07084896), Substudy 4 (NCT06655818), Substudy 5 (NCT07217184), Substudy 6 (NCT07150091), Substudy 7 (NCT07150104) and only contains data collected during screening phase (Day -30 to Day 0). Results are presented separately for each sub study.
Pre-assignment details
A total of 271 participants started the overall study which includes all participants who were screened for eligibility prior to enrollment. 208 participants met eligibility criteria and were randomized in the sub-studies.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 67.1 YEARS STANDARD_DEVIATION 8.89 |
| Race/Ethnicity, Customized All Other Races | 12 Participants |
| Race/Ethnicity, Customized Asian | 46 Participants |
| Race/Ethnicity, Customized Missing | 4 Participants |
| Race/Ethnicity, Customized White | 209 Participants |
| Sex: Female, Male Female | 122 Participants |
| Sex: Female, Male Male | 149 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
None listed