A Study of Belantamab Mafodotin in Combination With Nirogacestat and Pomalidomide in People With Multiple Myeloma That Has Not Responded to Treatment or Has Come Back After Treatment

NCT05556798 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 21-495
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to find out whether combination treatment with the study drugs belantamab mafodotin, nirogacestat, and pomalidomide is a safe treatment for people who have relapsed or refractory multiple myeloma. The researchers will test different doses of belantamab mafodotin to find the safest dose to give with nirogacestat and pomalidomide. The researchers also want to find out whether belantamab mafodotin plus nirogacestat and pomalidomide is an effective treatment for this type of bone marrow cancer, and the researchers will do tests that show whether the study treatment slows or stops the growth of cancer.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Belantamab Mafodotin; Nirogacestat; 21-495; Memorial Sloan Kettering Cancer Center; Pomalidomide

Outcome Measures

Primary Outcomes (1)

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

  The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized.

  up to six weeks

Secondary Outcomes (1)

• Clinical Response

  2 years

Study Arms (1)

Belantamab Mafodotin and Nirogacestat

EXPERIMENTAL

There will be a 1:1 randomization betweennirogacestat 100 mg BID or 100 mg QD during the 4day run-in period prior to starting belantamab mafodotin on Cycle 1 Day 1 (days -4 to -1). The cycle length for Cycles 1-3 is 21 days (3 weeks). Treatment with nirogacestat will be 100 mg BID continuously during each cycle for all subjects. Belantamab mafodotin will be administered via IV infusion in an outpatient setting on Day 1 of Cycles 1-3 and nirogacestat 100mg BID will be administered continuously on Days 1-21 of each cycle. Treatment with belantamab mafodotin will be given at an initial dose of 1.0 mg/kg. The study will have a 3+3 dose escalation design for belantamab mafodotin. Belantamab mafodotin dose levels are 1.0 mg/kg, 1.4 mg/kg, and 1.9 mg/kg. Pomalidomide was added, 2 mg to the 1.4 mg/kg and 1.9 mg/kg dose cohorts.

Drug: Belantamab Mafodotin; Drug: Nirogacestat; Drug: Pomalidomide

Interventions

Belantamab Mafodotin DRUG

Belantamab mafodotin will be administered via IV infusion in an outpatient setting on Day 1 of Cycles 1-3. Treatment with belantamab mafodotin will be given at an initial dose of 1.0 mg/kg. The study will have a 3+3 dose escalation design for belantamab mafodotin. Belantamab mafodotin dose levels are 1.0 mg/kg, 1.4 mg/kg, and 1.9 mg/kg

Also known as: GSK2857916

Belantamab Mafodotin and Nirogacestat

Nirogacestat DRUG

1:1 randomization between nirogacestat 100mg BID or 100 mg QD during the 4 day run-in period. Treatment with nirogacestat will be 100mg BID continuously during each cycle for all subjects.

Belantamab Mafodotin and Nirogacestat

Pomalidomide DRUG

After the 4-day run-in period, all patients will receive nirogacestat in combination with belantamab, mafodotin and pomalidomide. Pomalidomide was added for day 1-14 for cycle 1-3 and day 1-14 and day 21-35 for C4+.

Belantamab Mafodotin and Nirogacestat

Eligibility Criteria

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

You may qualify if:

• Patients with relapsed or refractory multiple myeloma treated with 3 or more prior lines of therapy. Relapsed/refractory multiple myeloma is defined by the International Myeloma Working Group (IMWG) updated criteria.
• Patients need to have measurable disease defined by one or more of the following:
• Serum myeloma (M)-protein greater than or equal to 0.5 g/dL (5 g/L).
• Urine M-protein ≥ 200 mg/24 h.
• Involved free light chain level ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65). Measurable plasmacytoma(s) verified by imaging or biopsy (≥1 lesion that has a single diameter of ≥2cm)
• e. A bone marrow biopsy demonstrating ≥30% infiltration of clonal plasma cells verified by CD138 immunohistochemistry.
• Have undergone autologous stem cell transplant or are considered transplant ineligible.
• Patients who have received prior CAR T cells are eligible. Patients who have received prior BCMA-directed therapy, other than belantamab mafodotin, are eligible. Patients who have received autologous stem cell transplantation \>60 days prior are eligible Patients who have received prior allogeneic stem cell transplantation \>100 days prior are eligible.
• Female or male patients age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2. PS-3 is permitted if PS is due solely to bone pain.
• Participants must enroll in and comply with the REMS program for pomalidomide.
• Fulfil the criteria for Adequate Organ System Function Based on Safety Assessments
• °Hematologic
• Absolute neutrophil count (ANC)a ≥1.0 × 10\^9/L
• Hemoglobin a ≥8.0 g/dL

You may not qualify if:

• Prior treatment with belantamab mafodotin
• Systemic anti-myeloma therapy (including systemic steroids) within ≤14 days, or plasmapheresis within 7 days prior to the first dose of study drug.
• Use of an investigational drug within 14 days or five half-lives (whichever is longer) preceding the first dose of study drug.
• Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs.
• Radiation therapy within 2 weeks prior to study entry (bone lesions requiring radiation may be treated with limited \[i.e., ≤ 25% of bone marrow in field\] radiation therapy during this period).
• Patients with a history of stem cell transplant autologous within 60 days or allogeneic within 100 days prior to study enrollment.
• Patients with AL amyloidosis will be excluded.
• Participant must not have had major surgery ≤4 weeks prior to initiating study treatment.
• Evidence of active mucosal or internal bleeding.
• Presence of active renal condition (infection or requirement for dialysis). Participants with isolated proteinuria resulting from multiple myeloma are eligible, provided they fulfill criteria given
• Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease per investigator's assessment).
• Participants with invasive malignancies other than multiple myeloma are excluded, unless the second malignancy has been considered medically stable for at least 2years. The participant must not be receiving active therapy, other than hormonal therapy for this disease with the exceptions of successfully treated non-metastatic basal cell, squamous cell skin carcinoma, or in-situ carcinoma.
• Evidence of cardiovascular risk including any of the following:
• Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities including 2nd degree (Mobitz Type II) or3rd degree atrioventricular (AV) block.
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk-Commack (Limited protocol activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Multiple Myeloma

Interventions

belantamab mafodotin; nirogacestat; pomalidomide

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

• Malin Hultcrantz, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: This is a phase Ib study with trial treatment is a combination of belantamab mafodotin (GSK2857916) and nirogacestat. A standard 3+3 dose escalation design with three planned doses of belantamab mafodotin will be implemented. There will be a 1:1 randomization between nirogacestat 100 mg BID or 100 mg QD during the 4 day run-in period prior to starting belantamab mafodotin on Cycle 1 Day 1 (days -4 to -1).

Study Record Dates

• First Submitted: September 22, 2022
• First Posted: September 27, 2022
• Study Start: October 4, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (7)