Efficacy and Safety Evaluation of Belantamab Mafodotin with Pomalidomide and Dexamethasone versus Pomalidomide, Bortezomib, and Dexamethasone in Relapsed/Refractory Multiple Myeloma
- Trial ID
- 2023-506877-37-00
- Protocol
- 207499
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the **efficacy** of the combination of belantamab mafodotin with pomalidomide and dexamethasone (B-Pd) against the combination of pomalidomide, bortezomib, and dexamethasone (PVd) in participants with **relapsed/refractory multiple myeloma** (RRMM). This comparison is clinically relevant as it aims to determine the more effective treatment regimen for improving patient outcomes in this challenging condition.
Secondary objectives include:
- Further comparison of the efficacy of B-Pd with PVd in participants with RRMM.
- Further assessment of the efficacy of B-Pd in terms of other efficacy outcomes in participants with RRMM.
- Evaluation of the safety and tolerability of B-Pd.
- Description of the exposure to belantamab mafodotin after infusion.
- Evaluation of the pharmacokinetics (PK) of pomalidomide in combination with belantamab mafodotin and dexamethasone in a subset of participants.
- Assessment of anti-drug antibodies (ADAs) against belantamab mafodotin.
- Evaluation of the safety and tolerability of belantamab mafodotin based on self-reported symptomatic adverse events when administered in combination with pomalidomide and dexamethasone.
- Evaluation and comparison of changes in symptoms and health-related quality of life (HRQoL).
Participants
The clinical trial involves a total of **147 participants** diagnosed with **relapsed/refractory multiple myeloma**. The study population includes both male and female subjects aged **18 years or older**. Participants were selected based on their ability to provide informed consent and adherence to protocol-defined contraceptive requirements. The trial includes individuals with an **Eastern Cooperative Oncology Group (ECOG) performance status** of 0 to 2, who have been previously treated with at least one prior line of multiple myeloma therapy, including a lenalidomide-containing regimen, and have documented disease progression. Participants must have undergone an autologous stem cell transplant (ASCT) more than 100 days prior to the first dose of study medication or be considered transplant ineligible. The trial population is characterized by adequate organ system functions and the absence of active bacterial, viral, or fungal infections. The study does not exclude vulnerable populations, and all prior treatment-related toxicities must be less than or equal to Grade 1 at the time of enrollment, except for alopecia. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed as a **randomized**, open-label, Phase III study to evaluate the efficacy and safety of **belantamab mafodotin** in combination with **pomalidomide** and **dexamethasone** (B-Pd) compared to **bortezomib** with pomalidomide and dexamethasone (PVd) in participants with **relapsed/refractory multiple myeloma**. The trial aims to compare the progression-free survival (PFS) between the two treatment groups, with secondary endpoints including overall survival (OS), duration of response (DoR), and overall response rate (ORR). The study is expected to run from October 2020 to February 2025, with participant involvement lasting until the end of the study or until disease progression or unacceptable toxicity occurs.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, previous treatment history, and measurable disease status. Following randomization, participants will attend regular follow-up visits to monitor treatment response and safety, including assessments of organ function and adverse events. The end-of-study visit will occur after the final treatment cycle or upon early termination, where final evaluations will be conducted. Conditions that may lead to early termination include disease progression, withdrawal of consent, or adverse events that compromise participant safety.
The trial employs a controlled methodology, with participants randomly assigned to either the B-Pd or PVd treatment arm. The study is not blinded, allowing both participants and investigators to know the treatment allocation. The trial's primary objective is to assess the efficacy of the B-Pd regimen compared to the PVd regimen, with a focus on improving PFS in the target population. The trial will also collect data on secondary outcomes, including the incidence of adverse events and changes in laboratory parameters, to provide a comprehensive evaluation of the treatment's safety profile.
Treatment
The clinical trial involves the administration of **Belantamab Mafodotin**, an experimental medication provided in the form of a **powder for solution for injection**. This medication is administered intravenously. The dosing schedule is based on a milligram per kilogram (mg/kg) basis, although specific dosage amounts are not provided. Belantamab Mafodotin is classified as a protein of other origin and is designated as an orphan drug with the number EU/3/17/1925. The product is developed by GlaxoSmithKline and is identified by the sponsor product code GSK2857916.
**Pomalidomide** is used as a non-experimental treatment in the study. It is available in hard capsule form with varying strengths of 1 mg, 2 mg, 3 mg, and 4 mg. The route of administration is oral. Pomalidomide is a chemical substance, and its administration is part of the standard-of-care therapy. The product is manufactured by Bristol-Myers Squibb Pharma EEIG and is identified by the marketing authorization numbers EU/1/13/850/001 to EU/1/13/850/004.
**Dexamethasone** is another non-experimental treatment used in the study. It is available in tablet form with strengths of 2 mg and 8 mg. The route of administration is oral. Dexamethasone is a chemical substance and is part of the comparator treatment. The product is manufactured by various companies, including Galenpharma GmbH, Mibe GmbH Arzneimittel, Aspen Pharma Trading Limited, and Teva UK Limited, with respective marketing authorization numbers.
**Bortezomib** is included as a comparator treatment in the study. It is provided as a powder for solution for injection, with a route of administration being subcutaneous. The dosing is based on a milligram per square meter (mg/m²) basis. Bortezomib is a chemical substance, and the product is manufactured by Janssen-Cilag International NV, identified by the marketing authorization number EU/1/04/274/001.
Participant compliance with the dosing schedules is monitored throughout the trial, although specific compliance measures are not detailed. The trial aims to evaluate the efficacy and safety of the combination of Belantamab Mafodotin with Pomalidomide and Dexamethasone (B-Pd) compared to Pomalidomide plus Bortezomib and Dexamethasone (PVd) in participants with relapsed/refractory multiple myeloma.
Efficacy
The efficacy of the clinical trial will be assessed using a range of primary and secondary endpoints. The primary endpoint is **Progression-Free Survival (PFS)**, which is defined as the time from randomization until the earliest date of progressive disease (PD) based on Independent Review Committee (IRC) assessment per International Myeloma Working Group (IMWG) criteria, or death due to any cause. Secondary endpoints include Overall Survival (OS), Duration of Response (DoR), Overall Response Rate (ORR), Complete Response Rate (CRR), and Very Good Partial Response (VGPR) or better rate. These endpoints are evaluated based on IRC assessment per IMWG criteria.
Additional secondary endpoints include Time to Best Response (TTBR), Time to Response (TTR), Time to Progression (TTP), and PFS2, which is defined as the time from randomization to disease progression after initiation of new anti-myeloma therapy or death from any cause. The trial will also assess the incidence of adverse events (AEs), changes in laboratory parameters, ocular findings on ophthalmic exams, and plasma concentrations of belantamab mafodotin and cys-mcMMAF. Derived pharmacokinetic (PK) parameter values and the incidence and titers of anti-drug antibodies (ADAs) against belantamab mafodotin will be measured as data permit.
Patient-reported outcomes will be evaluated using the maximum post-baseline PRO-CTCAE score for each item attribute and changes from baseline in health-related quality of life (HRQOL) as measured by EORTC QLQ-C30, EORTC QLQ-MY20, and EORTC IL52. The schedule for measuring these efficacy parameters will be aligned with the trial's protocol, ensuring systematic data collection and analysis throughout the study duration.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Capable of giving signed informed consent
- Male or female, 18 years or older
- Have a confirmed diagnosis of multiple myeloma (MM) as defined by the International Myeloma Working Group (IMWG) criteria
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Have been previously treated with at least 1 prior line of MM therapy including a lenalidomide-containing regimen and must have documented disease progression during or after their most recent therap. (Participants treated with lenalidomide ≥ 10mg daily for at least 2 consecutive cycles are eligible)
- Must have at least 1 aspect of measurable disease defined as one of the following: 1.Urine M-protein excretion greater than or equal to (≥)200 milligrams (mg) per 24-hour, or 2.Serum M-protein concentration ≥0.5 grams/deciliters (g/dL) (5 g/Liter [L]), or 3.Serum free light chain (FLC) assay: involved FLC level ≥10mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (less than [<]0,26 or greater than [>]1.65) only if participant has no measurable urine or serum M spike
- Have undergone autologous stem cell transplant (ASCT) or are considering transplant ineligible. Participants with a history of ASCT are eligible for study participation provided the following eligibility criteria are met: a. ASCT was >100 days prior to the first dose of study medication, b. No active bacterial, viral or fungal infection(s) present
- All prior treatment-related toxicities (defined by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0) must be less than or equal to (≤Grade 1 at the time of enrolment, except for alopecia
- Adequate organ system functions as mentioned in the protocol
- Male and female participants agree to abide by protocol-defined contraceptive requirements
Exclusion Criteria
- Active plasma cell leukaemia, symptomatic amyloidosis or active polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, and skin changes (POEMS) syndrome at the time of screening
- Prior allogeneic SCT
- Systemic anti-myeloma therapy (including chemotherapy and systemic steroids) within 14 days or five half-lives (whichever is shorter) preceding the first dose of study drug; prior treatment with a monoclonal antibody drug within 30 days of receiving the first dose of study drugs
- Plasmapharesis within 7 days prior to the first dose of study drug
- Received prior treatment with or intolerant to pomalidomide
- Received prior Beta cell maturation antigen (BCMA) targeted therapy
- Intolerant to bortezomib or refractory to bortezomib (for example; participant experienced progressive disease during treatment, or within 60 days of completing treatment, with a bortezomib-containing regimen of 1.3 mg/meter square [m^2] twice weekly)
- Evidence of cardiovascular risk including any of the following: 1.Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram abnormalities including second degree (Mobitz type II) or third degree atrioventricular (AV) block 2.Recent history (within 3 months of screening) of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting 3.Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system 4.Uncontrolled hypertension
- Any major surgery within the last 4 weeks
- Previous or concurrent invasive malignancy other than multiple myeloma, except: 1.The disease must be considered medically stable for at least 2 years; or 2.The participant must not be receiving active therapy, other than hormonal therapy for this disease
- Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment
- Evidence of active mucosal or internal bleeding
- Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, eoshageal or gastric varices, persistent jaundice
- Active infection requiring treatment
- Known or active human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C will be excluded unless the protocol-defined criteria are met
- Presence of active renal conditions (such as infection, severe renal impairment requiring dialysis or any other condition that could affect participant's safety)
- Ongoing Grade 2 peripheral neuropathy with pain within 14 days prior to randomization or ≥Grade 3 peripheral neuropathy
- Active or history of peripheral venous and arterial thromboebolism within the past 3 months
- Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis
- Current corneal disease except for mild punctate keratopathy
- Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures
- Pregnant or lactating female
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Recruiting | 01 Oct 2020 | 26 |
 France | Not Recruiting | 01 Oct 2020 | 3 |
 Germany | Not Recruiting | 01 Oct 2020 | 4 |
 Greece | Not Recruiting | 01 Oct 2020 | 50 |
 Italy | Not Recruiting | 01 Oct 2020 | 17 |
 Poland | Not Recruiting | 01 Oct 2020 | 15 |
 Spain | Not Recruiting | 01 Oct 2020 | 33 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Imnovid 3 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 0 | 1 | PRD9260806 |
Imnovid 4 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 0 | 1 | PRD9260808 |
Dexamethasone Tablets BP 2.0mg | Comparator | TABLETS | ORAL USE | 0 | 1 | PRD3570594 |
Dexamethason 8 mg GALEN®
Tabletten | Comparator | TABLETTEN | ORAL USE | 0 | 1 | PRD808394 |
Imnovid 2 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 0 | 1 | PRD9260805 |
Dexamethason 8 mg JENAPHARM® | Comparator | TABLET | ORAL USE | 0 | 1 | PRD988427 |
Dexamethasone 2mg Tablets | Comparator | TABLETS | SUBCUTANEOUS | 0 | 1 | PRD6599963 |
Imnovid 1 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 0 | 1 | PRD9260804 |
VELCADE 3.5 mg powder for solution for injection | Comparator | POWDER FOR SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 0 | 1 | PRD703624 |