Phase 2 study of belantamab mafodotin in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ceska Myelomova Skupina z.s.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Apr 2023 → ongoing

Decision date (initial)

2024-09-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

GlaxoSmithKline, United Kingdom

External identifiers

EU CT number

2024-516250-22-00

EudraCT number

2022-002515-34

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To optimize the dosing and schedule of belantamab mafodotin in combination with Vd in RRMM in order to achieve similar efficacy and ensure improved toxicity profile

Secondary objectives 1

1. 1.To further assess the efficacy of belantamab mafodotin in combination with Vd 2. To further assess the safety of belantamab mafodotin in combination with Vd 3. To describe the exposure to belantamab mafodotin when administered in combination with bortezomib and dexamethasone 4. To evaluate an alternate corneal AE management approach in hands of hematologist

Conditions and MedDRA coding

The study will enroll adult participants with RRMM who have been previously treated with at least 1 prior line of therapy, and who have documented disease progression during, or after, their most recent therapy.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1) Male or female, 18 years or older (at the time consent is obtained) 2) Confirmed diagnosis of multiple myeloma as defined by the IMWG criteria 3) Previously treated with at least 1 prior line of MM therapy, and must have documented disease progression during or after their most recent therapy 4) ECOG performance status of 0 to 2 5) No active infection(s) present 6) Participants with a history of autologous SCT: a. ASCT was >100 days prior to initiating study treatment 7) Must have at least ONE aspect of measurable disease, defined as one of the following: a. Urine M-protein excretion ≥200 mg/24h, or b. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or c. Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65). 8) All prior treatment-related toxicities (defined by NCI-CTCAE v5.0) must be ≤ Grade 1 at the time of enrollment, except for alopecia 9) Adequate organ system function as defined by the below laboratory assessments Hematologic o Absolute neutrophil count (ANC) ≥1.0 x 109/L; granulocyte colony-stimulating factor (G-CSF) use is NOT allowed to reach this level for the past 14 days. o Hemoglobin ≥ 8.0 g/dL; without blood transfusions for the past 14 days, erythropoietin is allowed. o Platelet count ≥75 x 109/L; blood transfusions or platelet stimulating agents for the past 14 days are NOT allowed to reach this level. Hepatic o Total bilirubin ≤1.5xULN (isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). o ALT ≤ 2.5xULN. Renal o eGFR ≥30 mL/min/1.73 m2; calculated using the Modified Diet in Renal Disease (MDRD) formula. o Spot urine (albumin/creatinine ratio) <500 mg/g (56 mg/mmol) OR o Urine Dipstick: Negative/trace; if ≥1+ only eligible if confirmed <500 mg/g [56 mg/mmol] by albumin/creatinine ratio (spot urine from first void). Female Participants: Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinicalstudies. Male Participants: Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion criteria 1

1. 1) Intolerant to bortezomib, or refractory to bortezomib (defined as progressive disease during treatment with a bortezomib-containing regimen of 1.3 mg/m2 twice weekly, or within 60 days of completing that treatment). Note: participants with progressive disease during treatment with a weekly bortezomib regimen are allowed. 2) Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain 3) Prior treatment with anti-BCMA therapy 4) Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs, or treatment with an investigational agent or approved systemic antimyeloma therapy (including systemic steroids) within 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is shorter 5) Plasmapheresis within 7 days prior to the first dose of study drug 6) Has received radiotherapy to a large pelvic area (check with sponsor). Bridging radiotherapy otherwise is allowed. 7) Prior allogenic stem cell transplant. 8) Any major surgery within 4 weeks prior to the first dose of study drug. Exception allowed for bone stabilizing surgery after consultation with medical monitor. 9) 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 fulfill criteria given in inclusion criterium number 9. 10) 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 to the study procedures 11) Evidence of active mucosal or internal bleeding 12) Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice 13) Previous or concurrent malignancies other than multiple myeloma, 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. 14) Evidence of cardiovascular risk including any of the following: Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities including second degree (Mobitz Type II) or third degree atrioventricular (AV) block 15) History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months before screening 16) Class III or IV heart failure as defined by the New York Heart Association functional classification system 17) Uncontrolled hypertension 18) Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, bortezomib, boron or mannitol or any other components of the study treatment 19) Active infection requiring treatment 20) Known HIV infection 21) Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HbcAb), at screening or within 3 months prior to first dose of study treatment. 22) Current corneal epithelial disease except for mild punctate keratopathy 23) Intolerance or contraindications to anti-viral prophylaxis 24) Symptomatic AL amyloidosis or active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. ORR, defined as the percentage of participants with a Partial Response (PR) or better (i.e., PR, Very Good Partial Response (VGPR), Complete Response (CR)) 2. Incidence rate of Grade ≥3 ocular adverse events according to the keratopathy visual acuity (KVA) scale

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ceska Myelomova Skupina z.s.

Sponsor organisation

Ceska Myelomova Skupina z.s.

Address

Jihlavska 340/20, Bohunice Bohunice

City

Brno

Postcode

625 00

Country

Czechia

Scientific contact point

Organisation

Ceska Myelomova Skupina z.s.

Contact name

Clinical Trial information desk

Public contact point

Organisation

Ceska Myelomova Skupina z.s.

Contact name

Clinical Trial information desk

Third parties 7

Locations

1 EU/EEA country · 7 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 6 files

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

Application history

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