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

NCT07084896 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: 208887 Sub Study 32023-509550-55
• Study Type: interventional
• Target: 106
• Locations: 13 countries
• Sites: 29

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

Keywords

Belantamab Mafodotin; Nirogacestat; GSK2857916; Multiple myeloma

Outcome Measures

Primary Outcomes (5)

• DE Phase: Number of Participants With Dose Limiting Toxicities (DLTs)

  Criteria for dose-limiting toxicity (DLT) included hematologic indicators such as Grade 3-5 febrile neutropenia and thrombocytopenia with bleeding. Non-hematologic criteria, excluding corneal toxicity, comprise Grade 3-5 toxicities, with exceptions for manageable nausea, vomiting, or diarrhea, controlled Grade 3 hypertension, and events linked to disease progression. Tumor lysis syndrome (TLS) of Grade 3 or 4, successfully managed within 7 days without end-organ damage, was considered. Corneal toxicity, assessed by the GSK corneal grading scale at Grade 4, is a DLT. Other organ-specific toxicities, notably liver toxicity meeting GSK stopping criteria, also qualified as DLTs. Severity was graded using National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

  Up to 28 days

• DE Phase: Number of Participants With Adverse Events (AEs)

  An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system.

  Up to approximately 253 weeks

• DE Phase: Number of Participants With Worst-case Hematology Results by Maximum Grade Increase Post - Baseline Relative to Baseline

  Blood samples were collected for evaluation of hematology parameters including Anemia (An), Hemoglobin increased (HbI), Lymphocyte count decreased (LyD), Lymphocytes count increased (LyI), Neutrophils count decreased (NeuD), Platelet count decreased (PD), Leukocytosis (LC) and White blood cell decreased (WBCD). The laboratory parameters were graded according to CTCAE v5.0. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3): severe; Grade 4 (G4) life-threatening or disabling. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Any worst-case post baseline increases to G1, G2, G3, and G4 are presented. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment.

  Baseline (Day 1) and up to approximately 253 weeks

• DE Phase: Number of Participants With Worst-Case Chemistry Results by Maximum Grade Increase Post - Baseline Relative to Baseline

  Blood samples were collected for evaluation of clinical chemistry parameters including Hypoglycemia (HG), Hypoalbuminemia (HA), Creatinine Kinase increased (CPKi), Hyperkalemia (HK), Blood lactate dehydrogenase Increased (BLDi), Hypermagnesemia (HyperM), Hypomagnesemia (HypoM), Hypernatremia (HyperN), Hypercalcemia (HyperC), Hypocalcemia (HypoC) and Chronic Kidney Disease (CKD). The laboratory parameters were graded according to CTCAE version 5. G1: mild; G2: moderate; G3: severe; Grade 4 (G4) life-threatening or disabling. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Any worst-case post baseline increase to G1, G2, G3, and G4 are presented. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment.

  Baseline (Day 1) and up to approximately 253 weeks

• CE Phase: Overall Response Rate (ORR)

  Overall Response Rate (ORR) was defined as the percentage of participants with a confirmed Partial Response (PR) or better as the best overall response (i.e., PR, Very Good Partial Response \[VGPR\], Complete Response \[CR\], and stringent Complete Response \[sCR\]), as assessed by the investigator per international myeloma working group (IMWG) (2016). PR is defined as ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 h. VGPR is defined as serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component \<100 mg/24 h. CR is defined as negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND \<5% plasmacytomas in the bone marrow. sCR is defined as CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.

  Up to approximately 253 weeks

Secondary Outcomes (29)

• DE Phase: Overall Response Rate (ORR)

  Up to approximately 253 weeks

• CE Phase: Clinical Benefit Rate (CBR)

  Up to approximately 253 weeks

• DE Phase: Number of Participants Achieving Stringent Complete Response (SCR), Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)

  Up to approximately 253 weeks

• CE Phase: Number of Participants Achieving SCR, CR, VGPR and PR

  Up to approximately 253 weeks

• DE Phase: Plasma Concentrations of Belantamab Mafodotin Antibody-Drug Conjugate (ADC)

  PRE-DOSE(PD), END OF INFUSION (EOI), EOI+2 HOURS(H), EOI+ 24H on Day(D) 1 of Cycle (C) 1; ANYTIME on C1 D4, D8, D22, and D29 ; PD and EOI on D1 of C2, C4, C6, C9, C12; PD on D1 of C18 and C30; End of Treatment (approximately 157 weeks)

Study Arms (1)

Belantamab mafodotin + Nirogacestat

EXPERIMENTAL

Drug: Belantamab mafodotin; Drug: Nirogacestat

Interventions

Nirogacestat DRUG

Nirogacestat will be administered.

Belantamab mafodotin + Nirogacestat

Belantamab mafodotin DRUG

Belantamab mafodotin will be administered.

Also known as: GSK2857916

Belantamab mafodotin + Nirogacestat

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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (29)

238995

Atlanta, Georgia, 30322, United States

Location

240593

Boston, Massachusetts, 02215, United States

Location

251164

Grand Rapids, Michigan, 49546, United States

Location

239015

Madison, Wisconsin, 53792, United States

Location

GSK Investigational Site

Fitzroy, Victoria, 3065, Australia

Location

GSK Investigational Site

Vancouver, British Columbia, V5Z1M9, Canada

Location

GSK Investigational Site

Halifax, Nova Scotia, B3H 1V7, Canada

Location

GSK Investigational Site

Lille, 59037, France

Location

GSK Investigational Site

Villejuif, 94805, France

Location

GSK Investigational Site

Frankfurt, 60590, Germany

Location

GSK Investigational Site

Kiel, 24105, Germany

Location

GSK Investigational Site

Leipzig, 04103, Germany

Location

GSK Investigational Site

Athens, 11528, Greece

Location

GSK Investigational Site

Utrecht, 3584 CX, Netherlands

Location

GSK Investigational Site

Oslo, 0450, Norway

Location

GSK Investigational Site

Katowice, 40-519, Poland

Location

GSK Investigational Site

Lodz, 93-513, Poland

Location

GSK Investigational Site

Lublin, 20-081, Poland

Location

GSK Investigational Site

Moscow, 125284, Russia

Location

GSK Investigational Site

Incheon, 21565, South Korea

Location

GSK Investigational Site

Seoul, 06351, South Korea

Location

GSK Investigational Site

Seoul, 06591, South Korea

Location

GSK Investigational Site

Ulsan, 44033, South Korea

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 31008, Spain

Location

GSK Investigational Site

Pozuelo de AlarcOn Madr, 28223, Spain

Location

GSK Investigational Site

Falun, SE-791 82, Sweden

Location

GSK Investigational Site

Stockholm, SE-141 86, Sweden

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

belantamab mafodotin; nirogacestat

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: July 22, 2025
• First Posted: July 25, 2025
• Study Start: June 8, 2020
• Primary Completion: April 17, 2025
• Study Completion (Estimated): March 11, 2027
• Last Updated: May 6, 2026
• Results First Posted: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); AU (1); NO (1); ES (4); PL (3); RU (1); SE (2); NL (1); CA (2); GR (1); FR (2); KR (4); US (4)