BELANTAMAB MAFODOTIN for Relapsed/Refractory Multiple Myeloma

Inclusion criteria

• {"criterion_text":"- 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.\n- Participants must be 18 or older, at the time of signing the ICF.\n- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Appendix 9).\n- 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\n- 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)\n- 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\n- Adequate organ system functions as defined in Table 9\n- 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.\n- 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

• {"criterion_text":"- Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes); active plasma cell leukemia at the time of screening.\n- History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.\n- Evidence of active mucosal or internal bleeding.\n- 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.\n- 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.\n- 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.\n- 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.\n- Pregnant or lactating female.\n- Active infection requiring treatment.\n- 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\n- Patients with Hepatitis B will be excluded unless the following criteria can be met (see protocol).\n- 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.\n- 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).\n- Participants unable to tolerate thromboembolic prophylaxis\n- Current corneal epithelial disease except for mild punctate keratopathy\n- Prior treatment with an anti-MM monoclonal antibody within 30 days prior to receiving the first dose of study intervention.\n- Prior BCMA-targeted therapy or prior pomalidomide treatment.\n- Plasmapheresis within 7 days prior to the first dose of study intervention\n- Prior allogeneic stem cell transplant. NOTE – Participants who have undergone syngeneic transplant will be allowed only if no history of, or currently active GvHD.\n- Any major surgery within the last 4 weeks.\n- 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.\n- 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."}

Primary endpoints

• {"endpoint_text":"- PFS, defined as the time from the date of randomization until the earliest date of documented disease progression (according to IMWG Response Criteria) or death due to any cause","definition_or_measurement_approach":"PFS measured from randomization to earliest documented disease progression per IMWG Response Criteria or death from any cause."}

Secondary endpoints

• {"endpoint_text":"- OS, defined as the time from randomization until death due to any cause","definition_or_measurement_approach":"Overall survival measured from randomization until death from any cause."}
• {"endpoint_text":"- ORR, defined as the percentage of participants with a confirmed PR or better per IMWG","definition_or_measurement_approach":"Objective response rate = percentage of participants with confirmed Partial Response (PR) or better according to IMWG criteria."}
• {"endpoint_text":"- Clinical benefit rate (CBR), defined as the percentage of participants with a confirmed Minimal response (MR) or better per IMWG","definition_or_measurement_approach":"CBR = percentage of participants with confirmed Minimal Response (MR) or better per IMWG."}
• {"endpoint_text":"- DoR, defined as the time from first documented evidence of PR or better until PD per IMWG or death due To any cause among participants who achieve confirmed PR or better","definition_or_measurement_approach":"Duration of response measured from first documented PR or better until disease progression per IMWG or death from any cause in responders."}
• {"endpoint_text":"- TTR, defined as the time between the date of randomization and the first documented evidence of response (PR or better) among participants who achieve confirmed PR or better","definition_or_measurement_approach":"Time to response measured from randomization to first documented PR or better among those achieving response."}
• {"endpoint_text":"- TTP, defined as the time from the date of randomization until the earliest date of documented PD (per IMWG response Criteria) or death due To PD","definition_or_measurement_approach":"Time to progression measured from randomization to earliest documented PD per IMWG or death due to PD."}
• {"endpoint_text":"- Incidence of adverse events (AEs) and changes in laboratory parameters","definition_or_measurement_approach":"Safety assessed by incidence, severity (NCI-CTCAE v5.0) of AEs and laboratory parameter changes."}
• {"endpoint_text":"- Ocular findings on ophthalmic exam","definition_or_measurement_approach":"Ophthalmic examinations to record ocular findings (planned ocular safety assessments per protocol)."}
• {"endpoint_text":"- Plasma concentrations of belantamab mafodotin, total mAb, and cys-mcMMAF","definition_or_measurement_approach":"Pharmacokinetic sampling to measure plasma concentrations of belantamab mafodotin, total monoclonal antibody and cys-mcMMAF."}
• {"endpoint_text":"- Incidence and titers of ADAs against belantamab mafodotin","definition_or_measurement_approach":"Assessment of anti-drug antibodies (ADA) incidence and titers against belantamab mafodotin."}
• {"endpoint_text":"- Symptomatic adverse effects as measured by the PRO-CTCAE and OSDI","definition_or_measurement_approach":"Patient-reported symptomatic AEs measured using PRO-CTCAE and Ocular Surface Disease Index (OSDI)."}
• {"endpoint_text":"- Health-related QOL as measured by EORTC QLQ-C30, EORTC IL52* and EORTC QLQ-MY20*","definition_or_measurement_approach":"Health-related quality of life assessed using EORTC QLQ-C30, EORTC IL52 and EORTC QLQ-MY20 instruments."}
• {"endpoint_text":"- MRD negativity rate, defined as; the percentage of participants who are MRD negative by NGS method","definition_or_measurement_approach":"Minimal residual disease (MRD) negativity rate assessed by next-generation sequencing (NGS) method; percentage MRD-negative participants."}

Germany

Latest Decision Or Authorization Date

11-06-2024

Number Of Sites

1

Number Of Participants

10

Spain

Latest Decision Or Authorization Date

06-06-2024

Number Of Sites

3

Number Of Participants

6

Poland

Latest Decision Or Authorization Date

17-06-2024

Number Of Sites

3

Number Of Participants

11

Italy

Latest Decision Or Authorization Date

10-06-2024

Number Of Sites

4

Number Of Participants

16

Hungary

Latest Decision Or Authorization Date

05-06-2024

Number Of Sites

6

Number Of Participants

26

Belgium

Latest Decision Or Authorization Date

05-06-2024

Number Of Sites

4

Number Of Participants

7

Netherlands

Latest Decision Or Authorization Date

07-06-2024

Number Of Sites

1

Number Of Participants

2

Greece

Latest Decision Or Authorization Date

22-07-2024

Number Of Sites

3

Number Of Participants

39

France

Latest Decision Or Authorization Date

05-06-2024

Number Of Sites

1

Number Of Participants

8

Bulgaria

Latest Decision Or Authorization Date

14-06-2024

Number Of Sites

2

Number Of Participants

16

Primary sponsor

Full Name

Glaxosmithkline Research & Development Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

IQVIA Limited

Responsibilities

DSURs submission to RAs except for BUL, SUSARs submission to RA's, Vendor management, Medical monitoring, payments, VT ocular services, COE Ophthalmology services and ePRO call Centre; additional operational duties (codes 1,2,3,5-12,15 as listed).

Name

Clario

Responsibilities

ePRO Questionnaires, Tablets, Site assessments, eLearning, Business Intelligence & Data transfer

Name

Parexel International (IRL) Limited

Responsibilities

Independent review committee of efficacy endpoints and pharmacogenomics data analysis

Name

Synchrogenix

Responsibilities

Patient Profiles & Narratives, data analysis and CSR

Name

IQVIA RDS Hellas Single Member S.A.

Responsibilities

Clinical monitoring, safety reporting and regulatory applications in Greece

Third parties

• {"country":"United Kingdom","full_name":"Veramed Limited","duties_or_roles":"sponsorDuties codes: 10 (role code provided in registry)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Triology Writing & Consulting GmbH","duties_or_roles":"sponsorDuties codes: 11","organisation_type":"Health care"}
• {"country":"United Kingdom","full_name":"Fishawack (new name Avalere Health)","duties_or_roles":"sponsorDuties codes: 11","organisation_type":"Health care"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Clario","duties_or_roles":"ePRO Questionnaires, Tablets, Site assessments, eLearning, Business Intelligence & Data transfer","organisation_type":"Industry"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Multiple sponsor duties including safety reporting, vendor management, medical monitoring, monitoring, payments, VT ocular services, COE Ophthalmology services, ePRO call centre and submissions (detailed in sponsor duties list)","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"Independent Review Committee of efficacy endpoints (including primary), Pharmacogenomics data analysis","organisation_type":"Pharmaceutical company"}
• {"country":"South Africa","full_name":"Synchrogenix","duties_or_roles":"Patient Profiles & Narratives, data analysis and CSR","organisation_type":"Health care"}
• {"country":"Greece","full_name":"IQVIA RDS Hellas Single Member S.A.","duties_or_roles":"Clinical Monitoring, Safety Reporting and Regulatory Applications in Greece","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Omnitrace Corp.","duties_or_roles":"Lost to follow-up Patient Search","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Veramed Limited (contact provided)","duties_or_roles":"Sponsor contact and support (contact: stephen.j.hope@gsk.com)","organisation_type":"Pharmaceutical company"}