A Phase 1/2, Dose and Schedule Evaluation Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin Administered in Combination With Daratumumab, Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Transplant Ineligible (EAE 120)
Overview
- Phase
- Phase 1
- Intervention
- Belantamab Mafodotin-Blmf
- Conditions
- Multiple Myeloma
- Sponsor
- Hellenic Society of Hematology
- Enrollment
- 36
- Locations
- 2
- Primary Endpoint
- Part 1: Dose-Limiting Toxicity (DLT)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a phase 1/2, open label, study designed to assess the safety and clinical activity of different belantamab mafodotin doses in combination with daratumumab, lenalidomide and dexamethasone.
The study will evaluate different doses of belantamab mafodotin in combination with daratumumab, lenalidomide and dexamethasone in 2 cohorts and will determine the recommended phase 2 dose (RP2D) to be further evaluated for safety and clinical activity in the dose expansion cohort. The RP2D dose will be used for future studies in the transplant ineligible newly diagnosed multiple myeloma setting.
Overall, approximately 36 participants will be enrolled in the study. Participant follow-up will continue up to 3 years after the last participant is randomized. The estimated accrual period will be 12 months corresponding to an approximate total study duration of 4 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant must be ≥ 18 years or older.
- •Monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytoma and documented MM satisfying at least one of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria:
- •CRAB criteria:
- •v. Hypercalcemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than upper limit of normal (ULN) or \>2.75 mmol/L (\>11 mg/dL).
- •vi. Renal insufficiency: creatinine clearance \<40mL/min or serum creatinine \>177 μmol/L (\>2 mg/dL).
- •vii. Anemia: hemoglobin \>2 g/dL below the lower limit of normal or hemoglobin \<10 g/dL.
- •viii. Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT.
- •Biomarkers of Malignancy:
- •d. Clonal bone marrow plasma cell percentage ≥60%. e. Involved: uninvolved serum free light chain (FLC) ratio ≥
- •f. More than 1 focal lesion on magnetic resonance imaging (MRI) studies.
Exclusion Criteria
- •Participants are excluded from the study if any of the following criteria apply:
- •Prior systemic therapy for MM, or SMM.
- •NOTE 1: An emergency course of steroids (defined as no greater than 40 mg of dexamethasone \[or equivalent\] per day for a maximum of 4 days \[that is, a total of 160 mg\]) is permitted.
- •NOTE 2: Focal palliative radiation is permitted prior to enrollment, provided that it occurred at least 2 weeks before the first dose of study drug, that the participant has recovered from radiation-related toxicities, and that the participant did not require corticosteroid administration (for a longer period than that specified in NOTE 1 above) for radiation-induced adverse events
- •Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute, Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version
- •Major surgery within 2 weeks before the first dose of study drug (NOTE: participant must be clinically stable following a major surgery to be entered in the study).
- •Presence of active renal condition (infection, requirement for dialysis, or any other significant condition that could affect participant's safety). Participants with isolated proteinuria resulting from MM are eligible, provided that they fulfil the other inclusion criteria.
- •Any serious and/or unstable pre-existing medical or psychiatric disorder, or other conditions (including laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures.
- •Evidence of active mucosal or internal bleeding uncontrolled by local therapy and not explained by reversible coagulopathy.
- •Current active unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. (except for Gilbert's syndrome or asymptomatic gallstones; otherwise stable non-cirrhotic chronic liver disease; or hepatobiliary involvement of malignancy as per the Investigator's assessment).
Arms & Interventions
Part 1: Dose Finding
Belantamab mafodotin will be administered as a combination therapy as a calculated dose on Day 1 of every other 28-day cycle. Belantamab mafodotin starting dose: 1. Cohort 1: 1.9 Q8W = 1.9 mg/kg on Day 1 of every other 28-day cycle 2. Cohort 2: 1.4 Q8W = 1.4 mg/kg on Day 1 of every other 28-day cycle Administration schedule for daratumumab 1800mg SC (fixed dose): Cycles 1-2: days 1, 8, 15, 22 Cycles 3-6: days 1, 15 Cycles 7+: day 1 Lenalidomide: 25 mg/d on day 1-21 of every 28-day cycle. Dexamethasone: 40 mg/d on days 1, 8, 15, 22 of every 28-day cycle in participants \< 75 years; 20 mg/d on days 1, 8, 15, 22 of every 28-day cycle in participants ≥ 75 years
Intervention: Belantamab Mafodotin-Blmf
Part 1: Dose Finding
Belantamab mafodotin will be administered as a combination therapy as a calculated dose on Day 1 of every other 28-day cycle. Belantamab mafodotin starting dose: 1. Cohort 1: 1.9 Q8W = 1.9 mg/kg on Day 1 of every other 28-day cycle 2. Cohort 2: 1.4 Q8W = 1.4 mg/kg on Day 1 of every other 28-day cycle Administration schedule for daratumumab 1800mg SC (fixed dose): Cycles 1-2: days 1, 8, 15, 22 Cycles 3-6: days 1, 15 Cycles 7+: day 1 Lenalidomide: 25 mg/d on day 1-21 of every 28-day cycle. Dexamethasone: 40 mg/d on days 1, 8, 15, 22 of every 28-day cycle in participants \< 75 years; 20 mg/d on days 1, 8, 15, 22 of every 28-day cycle in participants ≥ 75 years
Intervention: Daratumumab
Part 1: Dose Finding
Belantamab mafodotin will be administered as a combination therapy as a calculated dose on Day 1 of every other 28-day cycle. Belantamab mafodotin starting dose: 1. Cohort 1: 1.9 Q8W = 1.9 mg/kg on Day 1 of every other 28-day cycle 2. Cohort 2: 1.4 Q8W = 1.4 mg/kg on Day 1 of every other 28-day cycle Administration schedule for daratumumab 1800mg SC (fixed dose): Cycles 1-2: days 1, 8, 15, 22 Cycles 3-6: days 1, 15 Cycles 7+: day 1 Lenalidomide: 25 mg/d on day 1-21 of every 28-day cycle. Dexamethasone: 40 mg/d on days 1, 8, 15, 22 of every 28-day cycle in participants \< 75 years; 20 mg/d on days 1, 8, 15, 22 of every 28-day cycle in participants ≥ 75 years
Intervention: Lenalidomide
Part 1: Dose Finding
Belantamab mafodotin will be administered as a combination therapy as a calculated dose on Day 1 of every other 28-day cycle. Belantamab mafodotin starting dose: 1. Cohort 1: 1.9 Q8W = 1.9 mg/kg on Day 1 of every other 28-day cycle 2. Cohort 2: 1.4 Q8W = 1.4 mg/kg on Day 1 of every other 28-day cycle Administration schedule for daratumumab 1800mg SC (fixed dose): Cycles 1-2: days 1, 8, 15, 22 Cycles 3-6: days 1, 15 Cycles 7+: day 1 Lenalidomide: 25 mg/d on day 1-21 of every 28-day cycle. Dexamethasone: 40 mg/d on days 1, 8, 15, 22 of every 28-day cycle in participants \< 75 years; 20 mg/d on days 1, 8, 15, 22 of every 28-day cycle in participants ≥ 75 years
Intervention: Dexamethasone
Outcomes
Primary Outcomes
Part 1: Dose-Limiting Toxicity (DLT)
Time Frame: Up to 28 days
The number (%) of participants and 95% CI with the DLT in each of the cohorts 1-2, using the DLT evaluable population.
Part 1 and 2: Adverse Events (AEs) and Serious adverse events (SAEs)
Time Frame: Up to 4 years
The number (%) of participants with AEs and SAEs in each of the cohorts 1-2, using the DLT evaluable and Safety populations.
Part 1 and 2: Ocular toxicity
Time Frame: Up to 4 years
Number of participants with ocular toxicity of Grade 2 or higher (per KVA scale).
Part 2: Overall Response Rate (ORR)
Time Frame: Up to 4 years
ORR as per IMWG by Investigator assessment; defined as the percentage of participants with a confirmed partial response (PR), very good partial response (VGPR), complete response (CR) or stringent CR (sCR) (For the 'intention to treat' (ITT) population).
Secondary Outcomes
- Part 1: Overall Response Rate(Up to 4 years)
- Part 1 and 2: Lenalidomide Relative Dose Intensity (RDI)(Up to 4 years)
- Part 1 and 2: Cumulative dose of belantamab mafodotin(Up to 4 years)
- Part 1: Very good partial response(Up to 4 years)
- Part 1 and 2: Time to response (TTR)(Up to 4 years)
- Part 1 and 2: Duration of response(Up to 4 years)
- Part 1 and 2: Complete response rate (CRR)(Up to 4 years)
- Part 1 and 2: Minimal residual disease (MRD) negativity rate(Up to 4 years)
- Part 1 and 2: Progression free survival (PFS)(Up to 4 years)
- Part 1 and 2: Overall survival (OS)(Up to 4 years)
- Part 1 and 2: Abnormal ocular findings(Up to 4 years)
- Part 1 and 2: Pharmacokinetics (PK) analysis (PK population) - Peak plasma Concentration (Cmax)(Up to 4 years)
- Part 1 and 2: PK analysis (PK population) - Area under the plasma concentration versus time curve (AUC)(Up to 4 years)
- Part 1 and 2: Ocular Surface Disease Index (OSDI)(Up to 4 years)
- Part 1 and 2: Alternate corneal AE management(Up to 4 years)