A Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin in Combination With Daratumumab, Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Transplant Ineligible

NCT05280275 | Recruiting Phase 1

• 1 other identifier: EAE120
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

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.

Conditions

Multiple Myeloma; Neoplasms; Neoplasms, Plasma Cell; Gammopathy, Monoclonal; Paraproteinemias; Blood Protein Disorders; Haematologic Disease; Corneal Disease

Outcome Measures

Primary Outcomes (4)

• Part 1: Dose-Limiting Toxicity (DLT)

  The number (%) of participants and 95% CI with the DLT in each of the cohorts 1-2, using the DLT evaluable population.

  Up to 28 days

• Part 1 and 2: Adverse Events (AEs) and Serious adverse events (SAEs)

  The number (%) of participants with AEs and SAEs in each of the cohorts 1-2, using the DLT evaluable and Safety populations.

  Up to 4 years

• Part 1 and 2: Ocular toxicity

  Number of participants with ocular toxicity of Grade 2 or higher (per KVA scale).

  Up to 4 years

• Part 2: Overall Response Rate (ORR)

  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).

  Up to 4 years

Secondary Outcomes (15)

• 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

Study Arms (1)

Part 1: Dose Finding

EXPERIMENTAL

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

Drug: Belantamab Mafodotin-Blmf; Drug: Daratumumab; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Belantamab Mafodotin-Blmf DRUG

Blmf will be available as 100 mg/vial in single-use vial for reconstitution, supplied as lyophilized powder. Blmf will be delivered as IV solution over at least 30 minutes.

Part 1: Dose Finding

Daratumumab DRUG

Daratumumab will be administered with subcutaneous injections. On days where Blmf is given together with daratumumab, daratumumab should be performed first.

Part 1: Dose Finding

Lenalidomide DRUG

Lenalidomide will be administered per os.

Part 1: Dose Finding

Dexamethasone DRUG

Dexamethasone will be administered intravenously or per os.

Part 1: Dose Finding

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ≥100. f. More than 1 focal lesion on magnetic resonance imaging (MRI) studies.
• Must have at least ONE aspect of measurable disease, defined as one of the following:
• Urine M-protein excretion ≥200 mg/24 hrs (≥0.2 g/24 hrs), or
• Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or
• Serum FLC assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65).
• Not a candidate for high-dose chemotherapy with ASCT due to presence of significant comorbid condition(s), such as cardiac, pulmonary or other major organ dysfunction that are likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation. The participants will be assessed by the IMWG frailty index, a scoring system based on age, comorbidities and cognitive and physical conditions, which is recommended by the ESMO guidelines. Participants with IMWG frailty index score 1 or 2 will be considered transplant ineligible. The reason(s) for transplant ineligibility will be collected in the case report forms (CRFs).
• ECOG performance status of 0-2 (see Appendix 1).

You may not qualify if:

• 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 5.
• 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).
• 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).
• Participants with previous or concurrent malignancies other than MM are excluded. Exceptions are surgically treated cervical carcinoma in situ, or any other malignancy that 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.
• o 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:
• Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities, second degree (Mobitz Type II), or third degree atrioventricular (AV) block.
• Screening 12-lead ECG showing a baseline QT interval \>470 msec
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening.

Sponsors & Collaborators

• Hellenic Society of Hematology: lead
• GlaxoSmithKline: collaborator

Study Sites (2)

Department of Clinical Therapeutics, School of Medicine, National Kapodistrian University of Athens (NKUA)

Athens, 11528, Greece

RECRUITING

Anticancer Hospital of Thessaloniki "Theageneio"

Thessaloniki, 54639, Greece

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms; Neoplasms, Plasma Cell; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Corneal Diseases

Interventions

daratumumab; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Evangelos Terpos, Prof

  Department of Clinical Therapeutics, School of Medicine, National Kapodistrian University of Athens (NKUA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Pagoni, Dr

CONTACT

+302107211806; info@eae.gr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2022
• First Posted: March 15, 2022
• Study Start: April 13, 2022
• Primary Completion: March 15, 2026
• Study Completion: March 15, 2026
• Last Updated: December 1, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

GR (2)