A Study to Investigate the Safety and Efficacy of Belantamab for the Treatment of Multiple Myeloma When Used as Monotherapy and in Combination Treatments

Study Overview
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Brief Summary
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The study consists of three parts Part 1: The primary purpose of this part is to determine the safety, and recommended part 2 dose of belantamab (bela) in participants with relapsed or refractory multiple myeloma (RRMM). Part 2: The primary purpose of this part is to determine safety, tolerability and percentage of adverse events (AEs) that happen to eyes in participants with RRMM treated with bela in combination with other treatments. Part 3: The primary objective of this part is to assess the safety, tolerability and rate of ocular AEs in participants with transplant-ineligible newly diagnosed multiple myeloma (TI-NDMM) treated with either belantamab mafodotin (belamaf) or bela in combination with other treatments.

Official Title
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A Phase 1/2 Open-label, Multicentre, Dose Escalation and Expansion Study to Investigate the Safety, Tolerability, and Clinical Activity of Belantamab as Monotherapy and in Combination With Other Treatments in Participants With Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Bela
* Drug: Belamaf
* Drug: Lenalidomide
* Drug: Dexamethasone
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants at the time of signing the Informed Consent Form (ICF) are at least 18 years old or are of the legal age of consent in the jurisdiction in which the study is taking place. Participants who have histologically or cytologically confirmed diagnosis of Multiple Myeloma (MM), as defined by the IMWG, and measurable disease. PART 1: Participants who have received at least 3 prior lines of anti-myeloma treatments, and have already received an immunomodulating agent, a proteasome inhibitor, and an anti-CD38 mAb (unless contraindicated or unavailable). Lines of therapy are defined by consensus panel of the International Myeloma Workshop. PART 2: Participants who meet all of the following: Have undergone Autologous stem cell transplant (ASCT) or are considered transplant ineligible Have been previously treated with at least ONE prior line of MM therapy Have documented disease progression during or after their most recent therapy PART 3: Participants who meet both of the following: NDMM with a requirement for treatment as documented per IMWG criteria Not considered a candidate for high dose chemotherapy with ASCT due to: Age ≥ 65 years OR Age 18-65 years with presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT or who refuse high-dose chemotherapy with ASCT as an initial treatment. Participants capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and protocol. Exclusion Criteria: Diagnosis of primary Amyloid Light chain (AL) Amyloidosis, active Polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome, primary plasma cell leukemia. 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 with study procedures. Active infection requiring antibiotic, antiviral, or antifungal treatment. Known, current drug or alcohol abuse. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this trial, unless prospective Independent Review Board (IRB) approval (by chair or designee) is allowing exception to this criterion for a specific participant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 - Dose Escalation Phase in Participants with RRMM<br>Bela will be administered in participants with RRMM until progressive disease (PD). Participants may switch to Belamaf in case of PD. | Drug: Bela<br>* Bela will be administered.<br>* Other names: GSK2857914;Drug: Belamaf<br>* Belamaf will be administered.<br>* Other names: GSK2857916 BLENREP;|
| Experimental: Part 2 - Combination Treatments in Participants with RRMM<br>Participants with RRMM will receive Bela-xRd and Belamaf-xRd. The combination treatment xRd includes lenalidomide (R) and dexamethasone (d). x will be either a standard of care (SoC) or an emerging treatment for Multiple Myeloma. | Drug: Bela<br>* Bela will be administered.<br>* Other names: GSK2857914;Drug: Belamaf<br>* Belamaf will be administered.<br>* Other names: GSK2857916 BLENREP;Drug: Lenalidomide<br>* Lenalidomide will be administered.<br>Drug: Dexamethasone<br>* Dexamethasone will be administered.<br>Drug: Standard of Care<br>* Either standard of care (SoC) or an emerging treatment for Multiple Myeloma will be administered<br>|
| Experimental: Part 3 - Combination Treatments in Participants with TI-NDMM<br>Participants with TI-NDMM will receive Bela-xRd and Belamaf-xRd. The combination treatment xRd includes lenalidomide (R) and dexamethasone (d). x will be either a standard of care (SoC) or an emerging treatment for Multiple Myeloma. | Drug: Bela<br>* Bela will be administered.<br>* Other names: GSK2857914;Drug: Belamaf<br>* Belamaf will be administered.<br>* Other names: GSK2857916 BLENREP;Drug: Lenalidomide<br>* Lenalidomide will be administered.<br>Drug: Dexamethasone<br>* Dexamethasone will be administered.<br>Drug: Standard of Care<br>* Either standard of care (SoC) or an emerging treatment for Multiple Myeloma will be administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1, 2 and 3: Number of Participants with any Adverse Event |  | Up to 52 months | 
| Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) |  | Cycle 1 (Each cycle is of 28 days) | 
| Part 1, 2 and 3: Number of Participants with Worst Case Grade Change from Baseline in Laboratory and Vital Sign Parameters |  | Up to 52 months | 
| Part 2 and 3: Number of Participants with Corneal Adverse Events (CAEs) |  | Up to 52 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1, 2 and 3: Observed Plasma Concentration of Bela |  | Up to 52 months | 
| Part 1, 2 and 3: Area Under the Curve (AUC) of Bela |  | Up to 52 months | 
| Part 1, 2 and 3: Maximum Concentration (Cmax) of Bela |  | Up to 52 months | 
| Part 1, 2 and 3: Number of Participants with Anti-Drug Antibodies (ADA) against Bela |  | Up to 52 months | 
| Part 1, 2 and 3: Titers of ADA against Bela |  | Up to 52 months | 
| Part 2 and 3: Number of Participants with ADAs against Belamaf |  | Up to 52 months | 
| Part 2 and 3: Titers of ADAs against Belamaf |  | Up to 52 months | 
| Part 1, 2 and 3: Objective Response Rate (ORR) | ORR is defined as the percentage of participants with a confirmed Partial Response (PR) or better [i.e., PR, Very Good Partial Response (VGPR), Complete Response (CR), Stringent Complete Response (sCR)] as per International Myeloma Working Group (IMWG) criteria. | Up to 52 months | 
| Part 2 and 3: Stringent Complete Response (sCR) Rate | sCR is defined as the percentage of participants with CR plus normal free light chain ratio and absence of clonal cells in the bone marrow (BM) as per IMWG criteria. | Up to 52 months | 
| Part 2 and 3: Complete Response (CR) Rate | CR rate is defined as the percentage of participants with a confirmed CR or better (i.e., CR, sCR) as per IMWG criteria. | Up to 52 months | 
| Part 2 and 3: Very Good Partial Response (VGPR) Rate | VGPR rate is defined as the percentage of participants with a confirmed VGPR or better (i.e., VGPR, CR, sCR) as per IMWG criteria. | Up to 52 months | 
| Part 2 and 3: Observed Plasma Concentration of Belamaf |  | Up to 52 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bela, Belamaf, Belatamab, Belantamab Mafodotin, Relapsed or Refractory Multiple Myeloma, Transplant-ineligible newly diagnosed multiple myeloma