Evaluation of Alternative Dosing Regimens of Belantamab Mafodotin in Relapsed or Refractory Multiple Myeloma Patients
- Trial ID
- 2023-508213-16-00
- Protocol
- 209628
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to examine the **corneal events** associated with single-agent belantamab mafodotin using alternative dosing regimens in participants with relapsed or refractory **multiple myeloma** (RRMM) in Arms B to D compared to Arm A. This is clinically relevant as it aims to optimize the safety profile of belantamab mafodotin, potentially reducing ocular adverse events, which are a significant concern in the treatment of RRMM.
Secondary objectives include: - To further evaluate the corneal safety and tolerability of single-agent belantamab mafodotin in all arms. - To evaluate the efficacy of single-agent belantamab mafodotin in all arms. - To evaluate the overall safety and tolerability of single-agent belantamab mafodotin in all arms. - To assess the pharmacokinetics of single-agent belantamab mafodotin in all arms. - To assess anti-drug antibodies against single-agent belantamab mafodotin in all arms.
Participants
The clinical trial involves a total of **120 participants** diagnosed with **Multiple Myeloma**. The study population includes both male and female subjects, aged 18 years and older, who have a confirmed diagnosis of myeloma and have undergone or are ineligible for stem cell transplant. Participants have failed at least three prior lines of anti-myeloma therapies, including an anti-CD38 antibody, and are refractory to an immunomodulatory agent. The trial population was selected based on specific inclusion criteria, such as an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and a life expectancy of at least six months. Participants must have measurable disease and meet additional health criteria, including the absence of active infections and manageable treatment-related toxicities. Lifestyle considerations include adherence to contraceptive guidelines for both male and female participants, consistent with local regulations. The trial does not specify any particular dietary or physical activity requirements. The study includes a vulnerable population, ensuring that all participants are capable of providing informed consent.
Plans and Procedures
The clinical trial is a **Phase 2**, randomized, parallel, open-label study designed to evaluate the safety, efficacy, and pharmacokinetics of various dosing regimens of single-agent **belantamab mafodotin** in participants with relapsed or refractory **multiple myeloma**. The trial aims to examine corneal events associated with the drug using alternative dosing regimens. The study is expected to run from March 2022 to October 2025, with participant involvement lasting up to 1 year, depending on individual response and treatment tolerability.
Participants will be randomly assigned to one of the study arms, with the trial employing a controlled design to ensure robust data collection. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age, performance status, and prior treatment history; regular follow-up visits to monitor safety and efficacy outcomes; and an end-of-study visit to assess final outcomes and any long-term effects. The primary endpoint is the incidence rate of Grade ≥2 corneal events, while secondary endpoints include cumulative event rates, dose adjustments due to corneal events, and overall response rates.
Participants are expected to adhere to the study protocol, including scheduled visits and assessments. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. The study will ensure compliance with ethical standards, including informed consent and adherence to local regulations regarding contraception and pregnancy testing. The trial's design and procedures are structured to provide comprehensive data on the safety and efficacy of belantamab mafodotin in this patient population.
Treatment
The clinical trial involves the administration of **belantamab mafodotin**, an investigational medication developed by GlaxoSmithKline. This medication is provided in the form of a **powder for solution for injection**. The active substance, belantamab mafodotin, is a protein-based compound classified under "Protein - Other." The pharmaceutical form is specifically designed for **intravenous use**. The dosing regimen for this trial specifies a maximum daily dose of 2.5 mg/kg. The treatment period is limited to a maximum of one cycle, with the dosing schedule and frequency determined by the specific arm of the study in which the participant is enrolled. Compliance with the dosing regimen is monitored throughout the trial to ensure adherence to the protocol.
In this study, belantamab mafodotin is being evaluated as a single-agent therapy for participants with **relapsed or refractory multiple myeloma**. The trial is structured as a Phase 2, randomized, parallel, open-label study, with the primary objective of investigating the safety, efficacy, and pharmacokinetics of various dosing regimens. The study aims to assess corneal events associated with the administration of belantamab mafodotin, comparing alternative dosing regimens in different arms of the trial. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The trial is designed to provide comprehensive data on the investigational drug's performance in the specified patient population.
Efficacy
The efficacy of the clinical trial investigating **belantamab mafodotin** in participants with relapsed or refractory multiple myeloma will be assessed using a range of primary and secondary endpoints. The primary endpoint is the incidence rate of Grade ≥2 corneal events, evaluated according to the KVA scale. Secondary endpoints include the cumulative event rate of corneal events up to Week 16, incidence rate of corneal events by grade, and exposure-adjusted incidence rate of corneal events by grade, all measured using the KVA scale. Additional secondary endpoints involve the median duration of dose delay, percentage of participants requiring dose reductions, dose delays, and study treatment discontinuation due to corneal events, and the cumulative incidence of corneal events by grade.
Further secondary endpoints include the Toxicity Index by assessment/visit, percentage of time on study with corneal events, and change in Best Corrected Visual Acuity (ΔlogMAR). Efficacy will also be evaluated through overall response rate (ORR), defined as the percentage of participants with a confirmed partial response (PR) or better, and the percentage of participants with a confirmed very good partial response (VGPR) or better. Time to response (TTR), duration of response (DoR), time to progression (TTP), progression-free survival (PFS), and overall survival (OS) will also be assessed. The incidence of adverse events (AEs), including ocular AEs, and changes in laboratory parameters will be monitored, alongside the percentage of participants requiring dose modifications due to AEs. Pharmacokinetic parameters of belantamab mafodotin and the incidence and titers of anti-drug antibodies (ADAs) against belantamab mafodotin at each ADA time point will be analyzed as data permits.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant must be 18 years of age inclusive at the time of signing the Informed Consent Form (ICF).
- Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- "Participant has a histologically- or cytologically-confirmed diagnosis of myeloma as defined by IMWG criteria [Rajkumar, 2016], and a. Has undergone stem cell transplant or is considered transplant ineligible, and b. Has failed at least 3 prior lines of anti-MM therapies, including an anti?CD38 antibody (e.g., daratumumab) alone or in combination, and is refractory to an immunomodulatory agent (e.g., lenalidomide, pomalidomide)."
- "Participant has measurable disease with at least one of the following criteria: a. Serum M protein ≥ 0.5 g/dL (≥5 g/L), or b. Urine M protein ≥ 200 mg/24h, or c. Serum free light chain (FLC) assay: Involved FLC level ≥ 5 mg/dL (≥50 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)."
- "Participants with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: a. Transplant was >100 days before study enrollment, and b. Participant has no active infection(s), and c. Participant meets the remainder of the eligibility criteria outlined in protocol. "
- "All prior treatment-related toxicities (defined by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] Version 5.0) must be Grade ≤1 at the time of enrollment, except for alopecia and Grade 2 peripheral neuropathy. "
- Life expectancy of at least 6 months, in the opinion of the investigator.
- "Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Female Participants A female participant is eligible to participate if she is not pregnant or breastfeeding and at least one of the following conditions apply: • Is not a woman of childbearing potential (WOCBP) as defined in Section 10.9, or • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency (as described in Section 10.9) during the treatment period and for at least 4 months after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment. A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose (Cycle 1 Day 1) of study treatment (see Section 8.2.7). Additional requirements for pregnancy testing during and after study treatment are provided in Section 8.2.7 and the Schedule of Activities (SoA) (Section 1.3). The 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. b. Male Participants Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following conditions from the time of first dose of study treatment until 6 months after the last dose of study treatment to allow for clearance of any altered sperm: • Refrain from donating sperm, plus either: o 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 o Must agree to use contraception/barrier as follows: Agree to use a male condom, even if they have undergone a successful vasectomy, with female partner use of an additional highly effective contraceptive method with a failure rate of <1% per year as described in Section 10.9, when having sexual intercourse with a WOCBP (including pregnant females). "
- Participant is capable of giving signed informed consent as described in Section 10.10 which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
- Participant meets country-specific inclusion criteria described in Section 10.7, if applicable.
Exclusion Criteria
- Participant has symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes), or active plasma cell leukemia at the time of screening.
- Participant currently has corneal epithelial disease, except nonconfluent superficial punctate keratitis (SPK).
- Participant has evidence of active mucosal or internal bleeding.
- Participant has presence of an 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 fulfill adequate organ function inclusion criteria (Exclusion Criteria 24 in protocol).
- Participant has any serious and/or unstable pre-existing medical condition, psychiatric disorder, or other conditions (including laboratory abnormalities) that could interfere with the participant's safety, obtaining informed consent, or compliance with the study procedures.
- Participant has malignancies other than the disease under study are excluded, except for any other malignancy from which the participant has been disease-free for >2 years and, in the opinion of the principal investigator and GSK Medical Director, will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy (MM). Participants with curatively treated non-melanoma skin cancer may be enrolled without a 2-year restriction.
- Participant has evidence of cardiovascular risk including any of the following criteria: a. Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities including second degree (Mobitz Type II) or third degree atrioventricular block, or b. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting 3 months before screening, or c. Class III or IV heart failure as defined by the New York Heart Association functional classification system (see Section 10.11). d. Uncontrolled hypertension.
- Participant is a pregnant or lactating female.
- Participant has an active infection requiring antibiotic, antiviral, or antifungal therapy.
- Participant has known human immunodeficiency virus (HIV) infection, unless the participant can meet all of the following criteria: a. Established anti-retroviral therapy (ART) for ≥4 weeks and HIV viral load <400 copies/mL, and b. CD4+ T cell (CD4+) counts ≥350 cells/μL, and c. No history of acquired immunodeficiency syndrome-defining opportunistic infections within the last 12 months.
- Participants with hepatitis B virus (HBV) will be excluded unless the criteria in Table 5 can be met. (refer to the protocol section 5.2)
- Participants with a positive hepatitis C antibody test result or a positive hepatitis C virus (HCV) ribonucleic acid (RNA) test result at screening or ≥ 3 months before the first dose of study treatment will be excluded unless the participant can meet the following criteria: a. Negative HCV RNA test result b. Successful antiviral therapy (usually 8 weeks duration), followed by a negative HCV RNA test result after a washout period of ≥4 weeks.
- Participant has cirrhosis or current unstable liver or biliary disease per investigator assessment, defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice.
- Participant has alanine aminotransferase (ALT) >2.5× upper limit of normal (ULN).
- Participants has total bilirubin >1.5×ULN (isolated total bilirubin >1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
- Participant has received systemic anti-myeloma therapy within ≤14 days or 5 half lives, whichever is shorter, before the first dose of study treatment.
- Participant has received plasmapheresis 7 days before the first dose of study treatment.
- Participant has received systemic therapy with high dose steroids (equivalent to ≥60 mg prednisone daily for ≥4 days) administered to treat MM or non MM disease within ≤14 days before the first dose of study treatment.
- Participant has received a prior allogenic stem cell transplant.
- Participant has used an investigational drug ≤14 days or 5 half lives, whichever is shorter, before the first dose of study treatment or has received therapy with a monoclonal antibody ≤30 days before the first dose of study treatment, whichever is shorter. Note: Use of monoclonal antibodies for serious conditions unrelated to multiple myeloma, such as COVID, may be permitted after consultation with the GSK Medical Director.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 03 Mar 2022 | 7 |
 Germany | Not Recruiting | 03 Mar 2022 | 3 |
 Greece | Not Recruiting | 03 Mar 2022 | 9 |
 Ireland | Not Recruiting | 03 Mar 2022 | 2 |
 Italy | Not Recruiting | 03 Mar 2022 | 8 |
 Poland | Not Recruiting | 03 Mar 2022 | 22 |
 Spain | Not Recruiting | 03 Mar 2022 | 9 |