A study of a combination of Belantamab Mafodotin with Pomalidomide and Dexamethasone (B-Pd) compared to Bortezomib with Pomalidomide and Dexamethasone (PVd) in Participants with Relapsed/Refractory Multiple Myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Sep 2020 → ongoing

Decision date (initial)

2024-07-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GSK Research & Development Limited

External identifiers

EU CT number

2023-506877-37-00

EudraCT number

2018-004354-21

ClinicalTrials.gov

NCT04484623

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Efficacy, Safety, Pharmacodynamic, Pharmacokinetic

To compare the efficacy of B-Pd with that of PVd in participants with RRMM

Secondary objectives 8

1. To further compare the efficacy of B-Pd with that of PVd in participants with RRMM
2. To further assess the efficacy of B-Pd in terms of other efficacy outcomes in participants with RRMM
3. To evaluate the safety and tolerability of B-Pd
4. To describe the exposure to belantamab mafodotin after infusion
5. To evaluate the PK of pomalidomide in combination with belantamab mafodotin and dexamethasone, in a subset of participants
6. To assess ADAs against belantamab mafodotin
7. To evaluate the safety and tolerability of belantamab mafodotin based on selfreported symptomatic AEs when administered in combination with pomalidomide and dexamethasone
8. To evaluate and compare changes in symptoms and HRQoL

Conditions and MedDRA coding

Relapsed/Refractory Multiple Myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Capable of giving signed informed consent
2. Male or female, 18 years or older
3. Have a confirmed diagnosis of multiple myeloma (MM) as defined by the International Myeloma Working Group (IMWG) criteria
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
5. 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)
6. 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
7. 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
8. 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
9. Adequate organ system functions as mentioned in the protocol
10. Male and female participants agree to abide by protocol-defined contraceptive requirements

Exclusion criteria 22

1. 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
2. Prior allogeneic SCT
3. 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
4. Plasmapharesis within 7 days prior to the first dose of study drug
5. Received prior treatment with or intolerant to pomalidomide
6. Received prior Beta cell maturation antigen (BCMA) targeted therapy
7. 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)
8. 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
9. Any major surgery within the last 4 weeks
10. 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
11. 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
12. Evidence of active mucosal or internal bleeding
13. 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
14. Active infection requiring treatment
15. Known or active human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C will be excluded unless the protocol-defined criteria are met
16. Presence of active renal conditions (such as infection, severe renal impairment requiring dialysis or any other condition that could affect participant's safety)
17. Ongoing Grade 2 peripheral neuropathy with pain within 14 days prior to randomization or ≥Grade 3 peripheral neuropathy
18. Active or history of peripheral venous and arterial thromboebolism within the past 3 months
19. Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis
20. Current corneal disease except for mild punctate keratopathy
21. 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
22. Pregnant or lactating female

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-Free Survival (PFS), defined as the time from randomization until the earliest date of PD based on IRC-assessment per IMWG criteria, or death due to any caus

Secondary endpoints 16

1. Overall Survival (OS), defined as the interval of time from randomization to the date of death due to any cause
2. Duration of Response (DoR), defined as the time from first documented evidence of PR or better until progressive disease (PD) or death due to any progressive disease (PD) or death due to any per IMWG criteria. MRD negativity rate, defined as the percentage of participants who achieve MRD negative status (as assessed by NGS at 10-5 threshold) at least once during the time of confirmed CR or better response based on IRC-assessment per IMWG
3. Overall Response Rate (ORR,), defined as the percentage of participants with a confirmed partial response (PR) or better (i.e., PR, VGPR, CR, and sCR) based on IRC-assessment per IMWG criteria
4. Complete Response Rate (CRR,), defined as the percentage of participants with a confirmed complete response (CR) or better (i.e., CR and stringent complete response (sCR))) based on IRC assessment per IMWG criteria
5. Very Good Partial Response (VGPR) or better rate, defined as the percentage of participants with a confirmed VGPR or better (i.e., VGPR, CR, and sCR) based on IRC-assessment per IMWG criteria
6. Time to Best Response (TTBR), defined as the interval of time between the date of randomization and the earliest date of achieving best response among participants with a confirmed PR or better based on IRC-assessment per IMWG
7. Time to Response (TTR), defined as the time between the date of randomization and the first documented evidence of response (PR or better) among participants who achieve a response (i.e., confirmed PR or better) based on IRC-assessment per IMWG
8. Time to Progression (TTP), defined as the time from randomization until the earliest date of PD based on IRC-assessment per IMWG criteria, or death due to PD
9. PFS2, defined as time from randomization to disease progression (investigator-assessed response) after initiation of new anti-myeloma therapy or death from any cause, whichever is earlier. If disease progression after new antimyeloma therapy cannot be measured, a PFS event is defined as the date of discontinuation of new anti-myeloma therapy, or death from any cause, whichever is earlie
10. Incidence of AEs and changes in laboratory parameters
11. Ocular findings on ophthalmic exam
12. Plasma concentrations of belantamab mafodotin and cys-mcMMAF
13. Derived PK parameter values, as data permit
14. Incidence and titers of ADAs against belantamab mafodotin
15. Maximum post-baseline PRO-CTCAE score or each item attribute
16. Change from baseline in HRQOL as measured by EORTC QLQ-C30, EORT QLQ-MY20 and EORTC IL52

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 9

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trails Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trails Call Center

Third parties 21

Locations

7 EU/EEA countries · 35 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 215 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications