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A Study to Investigate Safety and Clinical Activity of Belantamab Mafodotin in Combination With Lenalidomide, Dexamethasone and Nirogacestat in Patients With Transplant Ineligible Newly Diagnosed Multiple Myeloma

ConditionsMultiple MyelomaNeoplasmsNeoplasm, Plasma CellGammopathy, MonoclonalParaproteinemiasBlood Protein DisordersHaematologic DiseaseCorneal Disease
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorHellenic Society of Hematology

About this trial

This is a phase 1/2, open-label study designed to assess the safety and clinical activity of different belantamab mafodotin doses in combination with lenalidomide, dexamethasone and nirogacestat in patients with transplant ineligible newly diagnosed multiple myeloma.

This will be a 2-part study. In part 1 participants will be enrolled in one cohort to receive belantamab mafodotin in combination with lenalidomide, dexamethasone and nirogacestat and will determine the recommended phase 2 dose (RP2D) to be further evaluated for safety and clinical activity in the dose expansion cohort. The RP2D dose will be used in future studies in the transplant-ineligible newly diagnosed multiple myeloma (NDMM) setting. In the dose expansion phase (Part 2) an expansion cohort will be treated with the RP2D. The expansion cohort will randomize participants (1:1) in two groups to evaluate two alternate dose modification guidelines for corneal AEs. Part 2 of the study will also evaluate an alternative dose modification guideline for corneal adverse events (AEs).

Overall, approximately 36 participants will be enrolled in the study. Participant follow-up will continue up to 3 years after the last participant is enrolled (follow-up period range: 3-4 years). The estimated accrual period will be 12 months, corresponding to an approximate total study duration of 4 years.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participant must be >18 years of age

Clonal BM plasma cell percentage ≥60%.

Involved: uninvolved serum free light chain (sFLC) ratio ≥100.

More than 1 focal lesion on magnetic resonance imaging (MRI) studies.

Disqualifiers

Prior systemic therapy for MM or Smoldering MM.

NOTE 1: An emergency course of steroids (defined as not greater than 40 mg of dexamethasone [or equivalent] per day for a maximum of 4 days [i.e., a total of 160 mg]) is permitted.

NOTE 2: Focal palliative radiation is permitted before enrollment, provided that: it occurred at least 2 weeks before the first dose of the study drug; the participant has recovered from radiation-related toxicities; and the participant did not require corticosteroid administration (for a longer period than that specified in NOTE 1 above) for radiation-induced AEs.

Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute Common Toxicity Criteria for AEs version 5.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Belantamab Mafodotin-Blmf

    Drug

    Blmf will be available as 100 mg/vial in single-use vial for reconstitution, supplied as lyophilized powder. Blmf will be delivered as IV solution over at least 30 minutes.

  • Lenalidomide

    Drug

    Lenalidomide will be administered per os.

  • Dexamethasone

    Drug

    Dexamethasone will be administered intravenously or per os.

  • Nirogacestat

    Drug

    Nirogacestat will be administrated each day for all subsequent cycles were Blmf is also administrated.

Treatment groups

36 Participants
are divided into 1 treatment group
Group A: Part 1 : Dose findingExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Part 1: Dose-Limiting Toxicity (DLT)

The number (%) of participants with DLTs using the DLT evaluable population.

Time frame
Up to 28 days
2

Part 1 and 2: Adverse Events (AEs) and Serious adverse events (SAEs)

The number (%) of participants with AEs and SAEs using the DLT evaluable and Safety populations

Time frame
Up to 4 years
3

Part 1 and 2: Ocular Toxicity

The number (%) of participants with grade 2 or above KVA events

Time frame
Up to 4 years
4

Part 2: Overall Response Rate (ORR)

ORR as per International Myeloma Working Group (IMWG) by Investigator Assessment; defined as the percentage of participants with a confirmed Partial Response (PR), Very Good Partial Response (VGPR), Complete Response (CR) or stringent Complete Response sCR in the intent-to-treat (ITT) set.

Time frame
Up to 4 years

Secondary outcomes

1

Part 1 and 2: Lenalidomide Relative Dose Intensity (RDI)

The RDI is defined as the percentage of the total administered over the total planned lenalidomide dose.

Time frame
Up to 4 years
2

Part 1 and 2: Nirogacestat Relative Dose Intensity (RDI)

The RDI is defined as the percentage of the total administered over the total planned nirogacestat dose.

Time frame
Up to 4 years
3

Part 1 and 2: Cumulative dose of bentalamab mafodotin

Cumulative administered dose of belantamab mafodotin in combination with lenalidomide, dexamethasone and nirogacestat i.e., the total dose of belantamab mafodotin that was administered.

Time frame
Up to 4 years
4

Part 1: Overall Response Rate (ORR)

Overall Response Rate as per IMWG by Investigator Assessment

Time frame
Up to 4 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Hellenic Society of Hematology

Lead sponsor

GlaxoSmithKline

Collaborator

Source ClinicalTrials.gov
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