Novel Combination of Belantamab Mafodotin and Elotuzumab to Enhance Therapeutic Efficacy in Multiple Myeloma

NCT05002816 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2000028918
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine if two drugs approved for treating multiple myeloma, belantamab mafodotin and elotuzumab, are safe and more effective when used together.

Conditions

Multiple Myeloma

Keywords

Belantamab Mafodotin; Elotuzumab

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of elotuzumab in combination with belantamab mafodotin in subjects

  Study patients will be enrolled and treated in cohorts of size 4 with maximum of 12 patients in the Phase I portion of the trial with possible dose de-escalation of belantamab mafodotin plus a fixed level of elotuzumab. Starting dose of belantamab mafodotin will be 1.9 mg/kg q4w. If the DLT rate hits de-escalation boundary (≥ 29.8%), four more patients will be enrolled for lower dose level with 1.9 mg/kg q8w; further dose reduction to 1.4mg/kg every 8 weeks will be planned for ongoing toxicity. Otherwise next cohort of 4 will be treated at same dose. The MTD will be determined once the maximum sample size of 12 for phase I portion is reached or stop the trial if 8 patients are treated at the initial dose without need of de-escalation.

  28 days

• Number of Participants who Experienced Dose-Limiting Toxicities (DLTs)

  DLT is defined as Grade 3 or greater febrile neutropenia lasting \>48 h despite adequate treatment, Grade 4 thrombocytopenia less than 25 accompanied by clinically significant bleeding, any Grade 3 or greater non-hematologic toxicity (other than corneal events) which is more severe than expected for an individual agent or which does not resolve with appropriate supportive treatment within 48 hours, any Grade 3 or greater non-hematologic laboratory value if the abnormality leads to hospitalization, grade 4 Keratopathy Visual Acuity (KVA) Scale, and liver toxicity meeting prespecified liver stopping criteria

  28 days

Secondary Outcomes (4)

• Preliminary evaluation of clinical efficacy/response rate

  Every 28 day cycle until progression up to 2 years

• To evaluate progression free survival (PFS)

  Followed for progression free survival until progression up to 2 years

• To evaluate overall survival (OS)

  Followed until loss of follow-up, withdrawal of consent, death from any cause, or termination of study up to 2 years

• To evaluate minimal residual disease (MRD) by multi-parameter flow cytometry and by next-generation sequencing (NGS)

  At follow-up visit (30 days +/-3 after discontinuation)

Study Arms (1)

Belantamab Mafodotin and Elotuzumab Arm

EXPERIMENTAL

Elotuzumab will be administered via intravenous infusion at an established dose of 10 mg/kg on days 1, 8, 15, 22 every 28 days for cycles 1 and 2, followed by 20mg/kg on day 1 of each cycle thereafter, cycles repeated every 28 days. Belantamab mafodotin will be administered via IV infusion. There will be 3 dose levels for belantamab mafodotin, with the starting dose of 1.9 mg/kg IV at every 4 week interval. Up to 12 subjects will be treated at this dose level. If the initial dose is found to be too toxic, dose of belantamab mafodotin 1.9 mg/kg every 8 weeks will be tested, further dose reduction to 1.4mg/kg every 8 weeks will be administered.

Drug: Elotuzumab; Drug: Belantamab mafodotin

Interventions

Elotuzumab DRUG

Elotuzumab will be administered via intravenous infusion at an established dose of 10 mg/kg on days 1, 8, 15, 22 every 28 days for cycles 1 and 2, followed by 20mg/kg on day 1 of each cycle thereafter, cycles repeated every 28 days.

Belantamab Mafodotin and Elotuzumab Arm

Belantamab mafodotin DRUG

Belantamab mafodotin will be administered via IV infusion on day 1 of each 28 day cycle. There will be 3 dose levels for belantamab mafodotin, with the starting dose of 1.9 mg/kg IV at every 4 week interval. Up to 12 subjects will be treated at this dose level. If the initial dose is found to be too toxic, dose of belantamab mafodotin 1.9 mg/kg every 8 weeks will be tested, further dose reduction to 1.4mg/kg every 8 weeks will be administered. Following the dose evaluation, there will be a dose expansion cohort wtih 12 additional subjects. There is no dose escalation planned in this study.

Belantamab Mafodotin and Elotuzumab Arm

Eligibility Criteria

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

You may qualify if:

• Participant must have MM that has relapsed after or is refractory to at least 3 prior lines of therapy. Relapsed/refractory disease as defined by IMWG criteria.
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Participant must be ≥ 18 years of age
• Prior line of therapy must include iMID, proteasome inhibitor, and anti-CD38 monoclonal antibody. Prior elotuzumab is allowed.
• Participant must have adequate organ function, defined as:
• ANC ≥0.5X 10 9/L
• Hemoglobin ≥8.0 g/dL
• Platelets ≥50X 10 9/L
• Total bilirubin ≤1.5X ULN (Isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
• ALT ≤2.5 X ULN
• eGRF ≥30 mL/min/ 1.73 m2
• Spot urine (albumin/creatinine ratios) \<500 mg/g (56 mg/mmol) OR
• Urine dipstick Negative/trace (if ≥1+ only eligible if confirmed \<500 mg/g (56 mg/mmol) by albumin/creatinine ratio (spot urine from first void)
• Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies::

You may not qualify if:

• Participant must not have current corneal epithelial disease except mild changes in corneal epithelium
• Participant must not have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria
• Participant must not use contact lenses while participating in this study
• Participant must not be simultaneously enrolled in any other interventional clinical trial
• Participant must not have used an investigational drug or approved systemic anti- myeloma therapy (systemic steroids are allowed) within 14 days preceding the first dose of study drug
• Participant must not have had plasmapheresis within 7 days prior to first dose of study treatment
• Participant must not have received prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs
• Participant must not have had major surgery ≤ 4 weeks prior to initiating study treatment
• Participant must not have any evidence of active mucosal or internal bleeding
• Participant must not have evidence of cardiovascular risk including any of the following:
• Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block.
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within three (3) months of Screening.
• Class III or IV heart failure as defined by the New York Heart Association functional classification system \[NYHA, 1994\]
• Uncontrolled hypertension
• Participant must not have known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment

Sponsors & Collaborators

• Yale University: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Yale New Haven Hospital

New Haven, Connecticut, 06512, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

elotuzumab; belantamab mafodotin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Natalia Neparidze, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalia Neparidze, MD

CONTACT

203-430-4881; natalia.neparidze@yale.edu

Carole Ramm

CONTACT

carole.ramm@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Medical Oncology, Hematology & Oncology

Study Record Dates

• First Submitted: July 21, 2021
• First Posted: August 12, 2021
• Study Start: February 21, 2022
• Primary Completion: January 30, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 30, 2025

Record last verified: 2025-09

Locations

US (1)