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Multiple MyelomaPhase 1NCT05556798

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

A Phase 1 study testing Belantamab Mafodotin, Nirogacestat and Pomalidomide in people with Multiple Myeloma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Belantamab Mafodotin, Nirogacestat and Pomalidomide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
7 sitesUnited States
Study dates
4 Oct 2022to Oct 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
  • A bone marrow biopsy demonstrating ≥30% infiltration of clonal plasma cells verified by CD138 immunohistochemistry.
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  • 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
  • Platelets a ≥50 × 10^9/L
  • °Hepatic
  • Total bilirubin ≤1.5 × ULN; (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%)
  • ALT ≤ 2.5 × ULN °Renal
  • eGFRb ≥30 mL/min^b
  • Spot urine (albumin/creatinine ratio from spot urine) ≤ 500 mg/g (56 mg/mmol) OR Urine dipstick Negative/trace (if ³1+ only eligible if confirmed <500 mg/g (56 mg/mmol) by albumin/creatinine ratio (spot urine from first void)
  • °Cardiac
  • Left Ventricular Ejection Fraction (LVEF) by ECHO ≥40% Note: Laboratory results obtained during Screening should be used to determine eligibility criteria. In situations where laboratory results are outside the permitted range, the Investigator may re-test the participant and the subsequent within range screening result may be used to confirm eligibility.
  • Without Growth factor support for the past 14 days, excluding erythropoietin. Transfusions are allowed
  • As calculated by the CKD-EPI formula.
  • Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤ 1,with the exception of peripheral neuropathy attributable to bortezomib.
  • Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
  • ° Is not a woman of childbearing potential (WOCBP)
  • Nonchildbearing potential is defined as follows (by other than medical reasons):
  • ° 45 years of age and has not had menses for >1 year
  • Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
  • Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.
  • OR
  • Is a WOCBP and agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, during the intervention period and for at least 4 months after the last dose of study intervention.
  • WOCBP must have a negative serum or urine pregnancy test within 72 hours prior to treatment with nirogacestat and must agree to use a highly effective method of contraception (i.e. copper-containing intrauterine device, established use of oral, inserted, injected or implanted hormonal method of contraception, or male/female sterilization, etc.)
  • WOCBP must agree not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
  • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy.
  • Male participants: Male participants are eligible to participate if they agree to the following during the intervention period and for 6 months after the last dose of study treatment to allow for clearance of any altered sperm: Male patients must use a condom when having sexual intercourse with a woman of childbearing potential(WOCBP) while receiving treatment with nirogacestat and for at least 6 months after the last dose. An additional form of highly effective contraception should also be used by the female partner, if of child-bearing potential
  • Signed and dated Informed Consent by study participant.
  • Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.

Who cannot join

  • 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.
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  • 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
  • Class III or IV heart failure as defined by the New York Heart Association functional classification system.
  • Uncontrolled hypertension
  • Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
  • Pregnant or lactating female.
  • Active infection requiring treatment.
  • Participant has known human immunodeficiency virus (HIV) infection, unless the participant can meet all of the following criteria:
  • Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load<400 copies/mL, and
  • CD4+ T-cell (CD4+) counts ≥350 cells/μL, and
  • No history of acquired immunodeficiency s-defining opportunistic infections within the last 12 months.
  • Note: Consideration must be given to ART and prophylactic antimicrobials that may have a drug-drug interaction and/or overlapping toxicities with belantamab mafodotin or other combination products as relevant.
  • Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb at Screening or within 3 months prior to first dose of study treatment). Note: Participants with positive Hepatitis B antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis B RNA test is obtained.
  • Positive hepatitis C antibody test result or positive hepatitis C RNA test result at Screening or within 3 months prior to first dose of study treatment. Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing
  • Current corneal disease except for mild punctate keratopathy. Note: Participants with mild punctate keratopathy are allowed.
  • Participant must not use contact lenses while participating in this study.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
  • Study participant has known malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of nirogacestat (e.g., gastric bypass, lap band, or other gastric procedures that would alter absorption); delivery of nirogacestat via nasogastric tube or gastrostomy tube is not allowed.
  • Concomitant administration of a strong or moderate CYP3A4 inhibitor or inducer within14 days prior to first dose of nirogacestat including foods such as seville oranges, grapefruit or hybrid. Please note that strong or moderate CYP3A inhibitor or inducer administration is to be prohibited during participation on study.
  • Concomitant administration of a strong CYP1A2 inhibitors while on treatment with pomalidomide.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

    Basking Ridge, New Jersey, 07920

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

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester (Limited Protocol Activities)

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)

    New York, New York, 10065

  • Memorial Sloan Kettering Nassau (Limited Protocol Activities)

    Uniondale, New York, 11553

Other trials in United States

About this study

Official title: Belantamab Mafodotin in Combination With Nirogacestat and Pomalidomide in Patients With Relapsed or Refractory Multiple Myeloma

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.

Being tested
Belantamab Mafodotin, Nirogacestat, Pomalidomide
Keywords
Multiple Myeloma, Belantamab Mafodotin, Nirogacestat, 21-495, Memorial Sloan Kettering Cancer Center, Pomalidomide
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Belantamab MafodotinDrug

    Also called GSK2857916

    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

  • NirogacestatDrug

    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.

  • PomalidomideDrug

    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+.

Study groups in NCT05556798
Study groupRoleWhat they receive
Belantamab Mafodotin and NirogacestatExperimentalThere will be a 1:1 randomization between nirogacestat 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.
Receives: Drug: Belantamab Mafodotin; Drug: Nirogacestat; Drug: Pomalidomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to six weeks

Secondary outcomes (1)

  1. Clinical Response

    Traditional Response Criteria from International Myeloma Working Group Criteria for Multiple Myeloma

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2022
  2. Study start4 Oct 2022
  3. Primary completionOct 2027 (estimated)
  4. Study completionOct 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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).
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05556798
Sponsor's protocol ID
21-495
Status last verified
Jul 2026
First submitted
22 Sep 2022
Last updated
21 Jul 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to:crdatashare@mskcc.org.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Belantamab Mafodotin, Nirogacestat and Pomalidomide in people with Multiple Myeloma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 40 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants who Experienced Dose-Limiting Toxicities (DLTs) (time frame: up to six weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05556798.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.

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