Efficacy and Safety Evaluation of Belantamab Mafodotin Versus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients
- Trial ID
- 2023-508962-14-00
- Protocol
- 207495
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the **efficacy** of belantamab mafodotin versus pomalidomide plus low-dose dexamethasone (pom/dex) in participants with relapsed/refractory multiple myeloma (RRMM). This comparison is clinically relevant as it aims to determine the potential of belantamab mafodotin as a more effective treatment option for RRMM, a condition characterized by the recurrence or resistance to standard therapies.
Secondary objectives include:
- Comparing the overall survival of participants treated with belantamab mafodotin versus pom/dex.
- Evaluating other markers of efficacy between the two treatment regimens.
- Assessing the safety and tolerability of belantamab mafodotin compared to pom/dex.
- Evaluating the pharmacokinetic profile of belantamab mafodotin.
- Assessing anti-drug antibodies (ADAs) against belantamab mafodotin.
- Evaluating the tolerability based on self-reported symptomatic adverse effects.
- Comparing changes in symptoms and health-related quality of life (HRQOL) between the treatments.
- Assessing Minimal Residual Disease (MRD) in participants achieving ≥VGPR or better with belantamab mafodotin versus pom/dex.
Participants
The clinical trial involves a total of **213 participants** diagnosed with **relapsed/refractory multiple myeloma**. The study population includes both male and female subjects, aged 18 years and older, with an **Eastern Cooperative Oncology Group (ECOG) performance status** ranging from 0 to 2. Participants have a confirmed diagnosis of multiple myeloma and have undergone at least two prior lines of anti-myeloma treatments. The selection criteria ensure that participants have measurable disease and adequate organ function. Lifestyle considerations include adherence to specific contraceptive measures for both male and female participants, consistent with local regulations, due to the potential risks associated with the study treatments. The trial population was selected based on their ability to provide informed consent and meet the outlined eligibility criteria, including a history of autologous stem cell transplant, if applicable. The study does not exclude vulnerable populations, indicating a comprehensive approach to participant selection.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of **belantamab mafodotin** compared to a combination of **pomalidomide** and low-dose **dexamethasone** in participants with relapsed/refractory multiple myeloma. This is a Phase III, open-label, randomized study. The trial is expected to run from its start date on April 2, 2020, until its estimated end date on April 1, 2026. Participants will be involved in the study for a maximum treatment period of 16 weeks, depending on the treatment arm they are assigned to.
The trial involves several key visits, starting with the inclusion (screening) visit, where participants are assessed for eligibility based on criteria such as age, performance status, and prior treatment history. Following randomization, participants will attend regular follow-up visits to monitor their response to treatment and any adverse events. The end-of-study visit will conclude the participant's involvement, where final assessments are conducted to evaluate the primary and secondary endpoints, including progression-free survival (PFS) and overall survival (OS).
Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent. The study is conducted under strict adherence to ethical guidelines, ensuring that all participants provide informed consent and meet the inclusion criteria, such as having a confirmed diagnosis of multiple myeloma and having undergone prior treatments. The trial's design and procedures are structured to ensure the collection of robust data to assess the comparative efficacy and safety of the investigational and comparator treatments.
Treatment
The clinical trial involves the administration of several treatments to evaluate their efficacy and safety in participants with **relapsed/refractory multiple myeloma**. The experimental medication, **Belantamab Mafodotin**, is provided as a powder for solution for injection. It is administered intravenously at a dosage of 2.5 mg/kg, with a maximum treatment period of 16 weeks. This medication is classified as an orphan drug and is produced by GlaxoSmithKline. Participant compliance with the dosing schedule is monitored throughout the trial.
In addition to the experimental treatment, the trial includes comparator treatments. **Pomalidomide**, marketed as Imnovid, is provided in hard capsule form with dosages of 1 mg and 4 mg. The maximum daily dose is 4 mg, and the total dose should not exceed 840 mg over a 10-day treatment period. This medication is administered orally and is produced by Bristol-Myers Squibb Pharma EEIG.
**Dexamethasone** is used as a standard-of-care therapy in this trial. It is available in various tablet forms, including Dexamethason 8 mg GALEN® Tabletten, Dexamethasone 2 mg Tablets, Dexamethason 8 mg JENAPHARM®, and Dexamethasone Tablets BP 2.0 mg. The maximum daily dose for dexamethasone is 40 mg, with a total dose limit of 1600 mg over a 10-day period. These tablets are administered orally and are produced by different manufacturers, including GALENPHARMA GMBH, TEVA UK LIMITED, MIBE GMBH ARZNEIMITTEL, and ASPEN PHARMA TRADING LIMITED.
Participant compliance with the administration of both experimental and comparator treatments is closely monitored to ensure adherence to the dosing schedules. The trial aims to provide comprehensive data on the efficacy and safety of these treatments in the specified patient population.
Efficacy
The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is **Progression-Free Survival (PFS)**, defined as the time from the date of randomization until the earliest date of documented disease progression according to the International Myeloma Working Group (IMWG) Response Criteria or death due to any cause. Secondary endpoints include Overall Survival (OS), Overall Response Rate (ORR), Clinical Benefit Rate (CBR), Duration of Response (DoR), Time to Response (TTR), Time to Progression (TTP), incidence of adverse events, ocular findings on ophthalmic exam, plasma concentrations of belantamab mafodotin, total monoclonal antibody (mAb), and cys-mcMMAF, incidence and titers of anti-drug antibodies (ADAs) against belantamab mafodotin, symptomatic adverse effects as measured by the PRO-CTCAE and OSDI, health-related quality of life as measured by EORTC QLQ-C30, EORTC IL52, and EORTC QLQ-MY20, and Minimal Residual Disease (MRD) negativity rate by NGS method.
These efficacy parameters will be measured and collected at various timepoints throughout the trial. The methods for assessing these endpoints include validated scales and laboratory tests. The trial is designed to compare the efficacy of belantamab mafodotin versus pomalidomide plus low-dose dexamethasone in participants with relapsed/refractory multiple myeloma. The trial will follow a structured schedule for data collection and analysis to ensure the reliability and validity of the results.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Capable of giving signed informed consent as described in Appendix 1 which includes compliance with requirements and restrictions listed in the ICF and in the protocol.
- Participants must be 18 or older, at the time of signing the ICF.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Appendix 9).
- Histologically or cytologically confirmed diagnosis of multiple myeloma (MM) as defined according to International Myeloma Working Group (IMWG), and: a. Has undergone autologous stem cell transplant (SCT), or is considered transplant ineligible, and b. Has received at least 2 prior lines of anti-myeloma treatments, including at least 2 consecutive cycles of both lenalidomide and a proteasome inhibitor (given separately or in combination), AND i) Must have documented disease progression on, or within 60 days of, completion of the last treatment OR ii) Must be non-responsive while on last treatment, where non-responsive is defined as not achieving at least Minimal Response (MR) after 2 complete treatment cycles. In such cases lack of achieving of at least MR must be determined no earlier than at least 4 weeks after the last treatment
- Has measurable disease with at least one of the following: a. Serum M-protein ≥0.5 g/dL (≥5 g/L) b. Urine M-protein ≥200 mg/24 hours c. Serum free light chain (FLC) assay: Involved FLC level ≥10 mg/dL (≥ 100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)
- Participants with a history of autologous SCT are eligible for study participation provided the following eligibility criteria are met: a. Transplant was >100 days prior to initiating study treatment b. No active infection(s) c. Participant meets the remainder of the protocol eligibility criteria
- Adequate organ system functions as defined in Table 9
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Male Participants: Male participants are eligible if they agree to the following during the Male participants are eligible if they agree to the following during the intervention period and until 6 months* after the last dose of study intervention to allow for clearance of any altered sperm: • Refrain from donating sperm PLUS, either: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR • Must agree to use a male condom throughout study treatment including the 6 month* follow-up period even if they have undergone a successful vasectomy and a female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as described in Appendix 4 when having sexual intercourse with a pregnant woman or a woman of childbearing potential (WOCBP) who is not currently pregnant. *4 weeks for male participants on Treatment Arm 2 (pom/dex). b. Female Participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a WOCBP [Appendix 4] OR • Is a WOCBP and agrees to abide by the following: • Arm 1 (belantamab mafodotin): Use a contraceptive method that is highly effective (with a failure rate of <1% per year) which includes abstinence, preferably with low user dependency during the intervention period and for 4 months after the last dose of study treatment. • Arm 2 (pom/dex): Due to pomalidomide being a thalidomide analogue with risk for embryofetal toxicity and prescribed under a pregnancy prevention/controlled distribution program, WOCBP participants will be eligible if they commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control (one method that is highly effective), beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy, during dose interruptions and continuing for at least 4 weeks following discontinuation of pomalidomide treatment. • 2 negative pregnancy tests must be obtained prior to initiating therapy. The 1st test should be performed within 10-14 days and the 2nd test within 24 hours prior to prescribing pomalidomide therapy. • And agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. • Investigator should confirm the effectiveness of the contraceptive method(s) ahead of the 1st dose of study intervention. Additional requirements for pregnancy testing during and after study intervention are located in Appendix 4. Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0, 2017) must be ≤Grade 1 at the time of enrollment, except for alopecia and Grade 2 peripheral neuropathy.
Exclusion Criteria
- Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes); active plasma cell leukemia at the time of screening.
- Systemic anti-myeloma therapy or use of an investigational drug within <14 days or 5 half-lives, whichever is shorter, before the first dose of study intervention.
- Prior treatment with an anti-MM monoclonal antibody within 30 days prior to receiving the first dose of study intervention.
- Prior BCMA-targeted therapy or prior pomalidomide treatment.
- Plasmapheresis within 7 days prior to the first dose of study intervention
- Prior allogeneic stem cell transplant. NOTE – Participants who have undergone syngeneic transplant will be allowed only if no history of, or currently active GvHD.
- Any major surgery within the last 4 weeks.
- 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 are eligible, provided they fulfil criteria included in Table 9 of the protocol.
- 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.
- History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
- Evidence of active mucosal or internal bleeding.
- Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria.
- Participants with previous or concurrent malignancies other than multiple myeloma are excluded, unless the second malignancy has been considered medically stable for at least 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease. NOTE – Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction.
- Evidence of cardiovascular risk including any of the following: a. Evidence of current clinically significant uncontrolled arrhythmias including clinically significant electrocardiogram (ECG) abnormalities including 2nd degree (Mobitz Type II) or 3rd degree atrioventricular block. b. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening. c. Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system (Appendix 10 of the protocol) d. Uncontrolled hypertension.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin, pomalidomide, dexamethasone or any of the components of the study intervention.
- Pregnant or lactating female.
- Active infection requiring treatment.
- Known human immunodeficiency virus (HIV), unless the participant can meet all of the following criteria: • Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/mL • CD4+ T-cell (CD4+) counts ≥350 cells/uL • No history of AIDS-defining opportunistic infections within the last 12 months
- Patients with Hepatitis B will be excluded unless the following criteria can be met (see protocol).
- Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment unless the participant can meet the following criteria (see protocol).
- Participants unable to tolerate thromboembolic prophylaxis
- Current corneal epithelial disease except for mild punctate keratopathy
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 02 Apr 2020 | 7 |
 Bulgaria | Not Recruiting | 02 Apr 2020 | 16 |
 France | Not Recruiting | 02 Apr 2020 | 8 |
 Germany | Not Recruiting | 02 Apr 2020 | 10 |
 Greece | Not Recruiting | 02 Apr 2020 | 39 |
 Hungary | Not Recruiting | 02 Apr 2020 | 26 |
 Italy | Not Recruiting | 02 Apr 2020 | 16 |
 The Netherlands | Not Recruiting | 02 Apr 2020 | — |
 Poland | Not Recruiting | 02 Apr 2020 | 11 |
 Spain | Not Recruiting | 02 Apr 2020 | 6 |
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 |
|---|---|---|---|---|---|---|
Dexamethason 8 mg GALEN®
Tabletten | Comparator | TABLETTEN | ORAL USE | 40 | 10 | PRD808394 |
Imnovid 1 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 4 | 10 | PRD9260804 |
Dexamethasone 2mg Tablets | Comparator | TABLETS | ORAL USE | 40 | 10 | PRD6599963 |
Dexamethason 8 mg JENAPHARM® | Comparator | TABLET | ORAL USE | 40 | 10 | PRD988427 |
Dexamethasone Tablets BP 2.0mg | Comparator | TABLETS | ORAL USE | 40 | 10 | PRD3570594 |
Imnovid 4 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 4 | 10 | PRD9260808 |