Study of Belantamab Mafodotin, Cevostamab, Pomalidomide for RRMM Patients (MAPLE)

NCT07831122 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: CMRG 011
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 7

Brief Summary

This study will evaluate efficacy and tolerability various doses of belantamab mafodotin in combination with cevostamab and pomalidomide in patients with multiple myeloma who have relapsed disease after two or more lines of therapy and/or have refractory to treatment disease.

Conditions

Relapsed Refractory Multiple Myeloma (RRMM)

Keywords

Multiple Myeloma Refractory; Multiple Myeloma Relapsed; belamaf; cevostamab; Belantamab Mafodotin; humanized IgG1 antibody-drug conjugate; humanized, full-length IgG1 anti-FcRH5/CD3; Relapsed/Refractory Multiple Myeloma; Myeloma; Multiple Myeloma; Blenrep

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose (RP2D)

  The Recommended Phase 2 Dose (RP2D) will be determined based on the incidence of dose-limiting toxicities (DLTs), overall tolerability, and preliminary antitumor activity. DLTs will be evaluated based on adverse events, clinical assessments, and laboratory test results.

  From the first dose of study drugs until the end of 3 cycles of therapy (up to 9 weeks; each cycle is 21 days) in the last dose-escalation cohort, or until study therapy is discontinued due to disease progression or toxicity, whichever occurs first.

• Overall Response Rate (ORR)

  Overall Response Rate (ORR) is defined as the proportion of participants who achieved a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) according to International Myeloma Working Group (IMWG) criteria.

  From 3 weeks after the first dose of study therapy (end of Cycle 1; Cycle 1 is 21 days) until the date of documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.

Secondary Outcomes (8)

• Progression Free Survival (PFS)

  From the date of the first dose of study therapy until the date of documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.

• Duration of Response (DOR)

  From the date of first documented partial response or better to the date of documented disease progression or death, whichever occurs first, assessed up to 24 months.

• Overall Survival (OS)

  From the date of the first dose of therapy until the date of death from any cause, assessed up to 24 months.

• Rates of Corneal Adverse Events

  From 1 day before receiving belamaf until the end of treatment or, if corneal findings are present, until corneal findings return to pre-treatment (baseline) condition or become stable, assessed up to 12 months.

• Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs)

  From 1 day before receiving study therapy until death from any cause or 90 days after discontinuation of study therapy, whichever occurs first.

Study Arms (2)

Belamaf + Cevostamab

EXPERIMENTAL

Belamaf + Cevostamab will be administrated on the dose escalation schedule in cycles: induction phase cycles are 21 days (Q3W) for 6 cycles followed by maintenance phase cycles, which are 42 days (Q6W). Up to 3 cohorts (Cohorts 1a-c) evaluating escalating doses of belamaf and cevostamab will be evaluated. (Cohort 1a - belamaf 1.9 mg/kg + cevostamab 90 mg; Cohort 1b - belamaf 1.9 mg/kg + cevostamab 160 mg; and Cohort 1c - belamaf 2.5 mg/kg + cevostamab 160 mg.) Treatment will continue until progression or unacceptable toxicity. Then, after the recommended phase 2 dose (RP2D) is determined, Cohort 2 will receive Belamaf + Cevostamab at the RP2D schedule in cycles: induction phase cycles are 21 days (Q3W) for 6 cycles followed by maintenance phase cycles, which are 42 days (Q6W). Treatment will continue until progression or unacceptable toxicity.

Drug: Belamaf; Biological: Cevostamab

Belamaf + Cevostamab+ Pomalidomide

EXPERIMENTAL

Belamaf + Cevostamab at RP2D with pomalidomide at 2 mg at 14/21 schedule in cycles: induction phase cycles are 21 days (Q3W) for 6 cycles followed by maintenance phase cycles, which are are 42 days (Q6W). pomalidomide on 14/21 schedule. Treatment will continue until progression or unacceptable toxicity.

Drug: Belamaf; Biological: Cevostamab; Drug: Pomalidomide

Interventions

Belamaf DRUG

Administered intravenously

Also known as: Belantamab mafodotin, GSK2857916

Belamaf + Cevostamab; Belamaf + Cevostamab+ Pomalidomide

Cevostamab BIOLOGICAL

Administered intravenously

Also known as: BFCR4350A

Belamaf + Cevostamab; Belamaf + Cevostamab+ Pomalidomide

Pomalidomide DRUG

Administered orally

Also known as: Pomalyst

Belamaf + Cevostamab+ Pomalidomide

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be able to understand and voluntarily sign an informed consent form (ICF).
• Must be ≥ 18 years of age at the time of signing the ICF.
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Documented diagnosis of MM and must have:
• (Part 1) relapsed and refractory disease having previously received 2 or more prior lines and having previously received lenalidomide, a proteosome inhibitor and/or anti-CD38 mAb (triple class exposed) and must be refractory to the last line of therapy.
• (Part 2) relapsed disease having previously received 1-3 prior line of therapy including lenalidomide, a proteosome inhibitor, and/or an anti-CD38 mAb .
• Lines of therapy are defined as per the consensus panel of the International Myeloma Workshop and include induction therapy followed by ASCT and consolidation/maintenance as one line.
• Relapse is defined as documented evidence of progressive disease (PD) after achieving at least stable disease (SD) for ≥ 1 cycle during a previous MM treatment (i.e., relapsed MM). and refractory is defined as disease progression during or within 60 days from the end of the most recent MM treatment.
• Subjects with measurable disease defined as at least one of the following (these baseline laboratory studies for determining eligibility must be obtained within 28 days prior to start of study drug):
• Serum M-protein ≥ 5 g/l
• Urine M-protein ≥ 200 mg/24 h
• Serum free light chains (FLC) assay: Involved FLC level ≥ 100 mg/l and an abnormal serum free light chain ratio (\< 0.26 or \> 1.65).
• Subjects with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met:
• \- Transplant was \> 100 days prior to study enrollment
• Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.

You may not qualify if:

• Prior treatment with bispecific or BCMA targeted antibody drug conjugate. Note prior anti-BCMA CAR T-cell therapy is permitted provided that the subject achieved a response of partial response (PR) or better and did not progress within 12 months of CAR T-cell infusion.
• Prior exposure to FcRH5 targeted therapy.
• Life-expectancy less than or equal to 12 weeks.
• WOCBP who are pregnant or lactating.
• Known history of amyloidosis, POEMS syndrome, active plasma cell leukemia (defined as circulating plasma cell count exceeding 500/uL or 5% of the peripheral blood white cells) at the time of screening.
• Inability to comply with protocol-mandated hospitalization and activities restrictions.
• History of allogeneic stem cell transplant.
• Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
• Evidence of active mucosal or internal bleeding.
• Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety).
• Subjects with previous or concurrent malignancies are allowed only if the second tumor is not contributing to the subject's illness and deemed to be at negligible risk of metastasis or death (e.g., expected 5-year OS ≥90%). Examples include ductal carcinoma in situ not requiring chemotherapy, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, low-grade, localized prostate cancer (Gleason score ≤7) not requiring treatment or appropriately treated Stage I uterine cancer. Subjects must be appropriately observed or managed/controlled are permitted onto study. The subject must not be receiving active therapy, other than hormonal therapy for this disease and the disease must be considered medically stable for at least 2 years.
• Current corneal epithelial disease except mild punctate keratopathy.
• History of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
• \- Note that patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
• Patients with history of confirmed progressive multifocal leukoencephalopathy (PML).

Sponsors & Collaborators

• Canadian Myeloma Research Group: lead
• GlaxoSmithKline: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (7)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

The Ottawa Hospital - General Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

UHN-Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Hospital Maisonneuve - Rosemont

Montreal, Quebec, H1T2M4, Canada

Location

McGill University Health Centre -MUHC

Montreal, Quebec, H4A 3J1, Canada

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

belantamab mafodotin; pomalidomide

Condition Hierarchy (Ancestors)

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

• Suzanne Trudel, MD

  UHN-Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heather Hiscock, MSc

CONTACT

416- 477-9849; cmrg@cmrg.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Part 1 (Cohorts 1 a-c) consists of a dose optimization and safety run-in phase of up to 3 cohorts evaluating escalating doses of belamaf and cevostamab. Part 2, Cohort 2 will evaluate the clinical activity and safety of the RP2D. Part 2, Cohort 3 to evaluate the RP2D with pomalidomide will be considered.

Study Record Dates

• First Submitted: September 2, 2026
• First Posted: September 21, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): January 1, 2033
• Study Completion (Estimated): March 1, 2033
• Last Updated: September 21, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7)