A Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin in Combination With Daratumumab, Pomalidomide and Dexamethasone in Patients With Relapsed/ Refractory Multiple Myeloma Previously Treated With One Line Therapy Who Are Lenalidomide Refractory

NCT05581875 | Not Yet Recruiting Phase 1

• 1 other identifier: EAE127
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase 1/2, open label, single-center study designed to assess the safety and preliminary clinical activity of different belantamab mafodotin doses in combination with daratumumab, pomalidomide, and dexamethasone (DPd) in patients with Relapsed/ Refractory Multiple Myeloma (RRMM) previously treated with one line of therapy who are lenalidomide refractory. This will be a 2-Part study. Part 1 will evaluate the safety of belantamab mafodotin in combination with DPd in 2 cohorts and determine the Recommended Phase 2 Dose (RP2D). In the dose expansion phase (Part 2) an expansion cohort will be treated with the RP2D. The expansion cohort will randomize participants (1:1) in two groups to evaluate two alternate dose modification guidelines for corneal AEs. Part 2 will further evaluate the safety and assess the preliminary clinical activity of the belantamab mafodotin RP2D in combination with DPd. Overall, approximately 48 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; Multiple Myeloma in Relapse; Neoplasms; Gammopathy, Monoclonal; Paraproteinemias; Blood Protein Disorders; Haematologic Disease; Corneal Disease; Neoplasms, Plasma Cell

Outcome Measures

Primary Outcomes (4)

• Part 1: Dose-Limiting Toxicity (DLT)

  The number (percent) of participants with DLTs using the DLT evaluable population.

  Up to 28 days

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

  The number (percent) of participants with AEs and SAEs using the DLT evaluable and Safety populations.

  Up to 4 years

• Part 1 and 2: Ocular Toxicity

  The number (percent) of participants with Grade ≥2 ocular toxicity per Keratopathy Visual Acuity (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 (22)

• Part 1 and 2: Cumulative dose of belantamab mafodotin

  Up to 4 years

• Part 1: Overall Response Rate (ORR)

  Up to 4 years

• Part 1: Very good partial response (VGPR)

  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

Study Arms (1)

Part 1 : Dose finding

EXPERIMENTAL

Belantamab mafodotin will be administered by intravenous infusion as a combination therapy as a calculated dose on Day 1 of every other 28-day cycle. Belantamab mafodotin starting dose for Part 1: * Cohort 1: 1.4 Q8W = 1.4 mg/kg on Day 1 of every other 28-day cycle * Cohort 2: 1.9 Q8W = 1.9 mg/kg on Day 1 of every other 28-day cycle Daratumumab 1800mg SC (fixed dose) on: Cycles 1-2: days 1, 8, 15, 22 Cycles 3-6: days 1, 15 Cycles 7+: day 1 Pomalidomide: 4 mg/d on days 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: Pomalidomide; 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

Pomalidomide DRUG

Pomalidomide 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.
• Documented diagnosis of Multiple Myeloma (MM) as per International Myeloma Working Group (IMWG) criteria.
• 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 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).
• Eastern Cooperative Oncology Group performance status of 0-2.
• Adequate organ system function as defined by the below laboratory assessments. Hematologic
• Absolute neutrophil count (ANC) ≥1.5 X 109/L; granulocyte colony stimulating factor use within the past 14 days is NOT permitted.
• Hemoglobin ≥8.0 g/dL; transfusions within the past 14 days are NOT permitted. Erythropoietin use is allowed.
• Platelet count ≥50 x 109/L if Bone Marrow (BM) is \>50% involved in myeloma. Otherwise ≥75 x 109/L; transfusions within the past 14 days are NOT allowed to reach this level.
• Hepatic
• Total bilirubin ≤1.5xULN (isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Alanine aminotransferase (ALT) ≤ 2.5xUpper Limit of Normal (ULN). Renal
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You may not qualify if:

• 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 4 weeks before the first dose of study drug
• NOTE 1: participant must be clinically stable following a major surgery to be entered in the study.
• NOTE 2: major surgery shall be defined based on the Investigator's judgment according to the extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes.
• 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.
• 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 electrocardiogram (ECG) abnormalities, second degree (Mobitz Type II), or third degree atrioventricular 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.
• Class III or IV heart failure as defined by the New York Heart Association functional classification system
• Uncontrolled hypertension.

Sponsors & Collaborators

• Hellenic Society of Hematology: lead
• GlaxoSmithKline: collaborator

MeSH Terms

Conditions

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

Interventions

daratumumab; pomalidomide; 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)

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: October 5, 2022
• First Posted: October 17, 2022
• Study Start: October 20, 2022
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: October 17, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share