Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat in Participants With RRMM

NCT ID: NCT07084896

Last Updated: 2025-07-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-08
• Study Completion Date: 2027-03-11

Brief Summary

The primary purpose is to determine the safety and tolerability of belantamab mafodotin in combination with nirogacestat and to establish the recommended Phase 2 dose for combination treatment to explore in the cohort expansion (CE) phase in participants with RRMM. This study is a sub study of the Master protocol (NCT04126200).

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Belantamab mafodotin + Nirogacestat

Group Type: EXPERIMENTAL

Belantamab mafodotin

Intervention Type: DRUG

Belantamab mafodotin will be administered.

Nirogacestat

Intervention Type: DRUG

Nirogacestat will be administered.

Interventions

Belantamab mafodotin

Belantamab mafodotin will be administered.

Intervention Type: DRUG

Nirogacestat

Nirogacestat will be administered.

Intervention Type: DRUG

Other Intervention Names

GSK2857916

Eligibility Criteria

Inclusion Criteria

Participant must be 18 years of age inclusive or older, at the time of signing the informed consent.

• Participants must have histologically or cytologically confirmed diagnosis of Multiple Myeloma (MM), as defined by the IMWG.
• Participants having at least 3 prior lines of prior anti-myeloma treatments including an immunomodulating agent (IMID) a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody.
• Participants with a history of autologous stem cell transplant are eligible for study participation when, transplant was >100 days prior to study enrolment and with no active infection(s).
• Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, unless ECOG less than equal to (<=)2 is due solely to skeletal complications and/or skeletal pain due to MM.
• Participants with measurable disease defined as at least one of the following: Serum M-protein greater than equal to (>=)0.5 gram per deciliter (>=5 gram per liter) or Urine M-protein >=200 milligrams (mg) per 24 hours or Serum free light chain (FLC) assay: Involved FLC level >=10 mg per deciliter (>=100 mg per Liter) and an abnormal serum FLC ratio (<0.26 or >1.65).
• Participants who have tested positive for Hepatitis B core antibody (HBcAb) can be enrolled if the following criteria are met: Serology result HBcAb+, Hepatitis B surface antigen (HBsAg)-; HBV deoxyribonucleic acid (DNA) undetectable during screening.
• Participants who are currently receiving physiological doses oral steroids (<10 mg/day), inhaled steroids or ophthalmological steroids.

Exclusion Criteria

Participants with current corneal epithelial disease except mild punctate keratopathy.

• Participants with evidence of cardiovascular risk.
• Participants with known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin or any of the components of the study treatment. History of severe hypersensitivity to other mAb.
• Participants with active infection requiring antibiotic, antiviral, or antifungal treatment.
• Participants with other monoclonal antibodies within 30 days or systemic anti-myeloma therapy within <14 days.
• Participants with prior radiotherapy within 2 weeks of start of study therapy.
• Participants with prior allogeneic transplant are prohibited.
• Participants who have received prior Chimeric Antigen T cell therapy (CAR-T) therapy with lymphodepletion with chemotherapy within 3 months of screening.
• Participants with any major surgery (other than bone-stabilizing surgery) within the last 30 days.
• Participants with prior treatment with an investigational agent within 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is shorter.
• Participants with >=grade 3 toxicity considered related to prior check-point inhibitors and that led to treatment discontinuation.
• Participants who have received transfusion of blood products within 2 weeks before the first dose of study drug.
• Participants must not receive live attenuated vaccines within 30 days prior to first dose of study treatment or whilst receiving belantamab mafodotin +- partner agent in any sub-study arm of the platform trial and for at least 70 days following last study treatment.
• Participants with presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety). Participants with isolated proteinuria resulting from MM.
• Participants with known human immunodeficiency virus (HIV) infection, unless the participant can meet all criteria: a) established anti-retroviral therapy for at least 4 weeks and HIV viral load<400 copies/milliliter (mL) b) cluster of differentiation 4 plus (CD4+) T-cell (CD4+) counts >= 350 cells/microliter (µL) c) No history of Acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the last 12 months in which case the participant would be eligible for CE Phase only.
• Participants with uncontrolled small and/or large intestinal disease.
• Participants with uncontrolled skin disease.
• Participants with any condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement.
• Participants with previous administration of a gamma secretase inhibitor.
• Participants with concomitant administration of a strong CYP3A4 inhibitor or inducer.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

238995

Atlanta, Georgia, United States

240593

Boston, Massachusetts, United States

251164

Grand Rapids, Michigan, United States

239015

Madison, Wisconsin, United States

GSK Investigational Site

Fitzroy, Victoria, Australia

GSK Investigational Site

Vancouver, British Columbia, Canada

GSK Investigational Site

Halifax, Nova Scotia, Canada

GSK Investigational Site

Lille, , France

GSK Investigational Site

Villejuif, , France

GSK Investigational Site

Frankfurt, , Germany

GSK Investigational Site

Kiel, , Germany

GSK Investigational Site

Leipzig, , Germany

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Utrecht, , Netherlands

GSK Investigational Site

Oslo, , Norway

GSK Investigational Site

Katowice, , Poland

GSK Investigational Site

Lodz, , Poland

GSK Investigational Site

Lublin, , Poland

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Incheon, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Ulsan, , South Korea

GSK Investigational Site

Badalona, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Pozuelo de AlarcOn Madr, , Spain

GSK Investigational Site

Falun, , Sweden

GSK Investigational Site

Stockholm, , Sweden

Countries

United States; Australia; Canada; France; Germany; Greece; Netherlands; Norway; Poland; Russia; South Korea; Spain; Sweden

Other Identifiers

2023-509550-55

Identifier Type: OTHER

Identifier Source: secondary_id

208887 Sub Study 3

Identifier Type: -

Identifier Source: org_study_id