An open label, multicenter, phase II study of belantamab mafodotin in combination with VRd for the treatment of newly diagnosed transplant eligible multiple myeloma patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Pethema

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 Sep 2024 → 3 Mar 2026

Decision date (initial)

2024-09-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516130-35-00

EudraCT number

2020-002050-24

ClinicalTrials.gov

NCT04802356

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

The primary objective of this study is to evaluate the safety and tolerability of belantamab mafodotin when administered in combination with VRd in newly diagnosed (ND) transplant eligible MM patients.

Secondary objectives 2

1. To assess the efficacy of belantamab mafodotin in combination with VRd in terms of efficacy outcomes in participants with NDMM who are transplant eligible.
2. To evaluate the efficiency of collection of CD34 cells after 2 induction cycles of belantamab mafodotin and 4 induction cycles with VRd.

Conditions and MedDRA coding

Multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participant must have Newly diagnosed multiple myeloma. Newly diagnosed subjects must have symptomatic disease following the IMWG updated criteria (Rajkumar Lancet 2014, Appendix 6).
2. Participant must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200 mg/24 h. For patients whose disease is only measurable by serum FLC, the involved FLC should be ≥ 100mg/L (10 mg/dl), with an abnormal serum free light chain ratio (<0.26 or >1.65)ratio.
3. Newly diagnosed participants must be eligible for stem cell transplant at investigator criteria.
4. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
5. Participant must be ≥ 18 years of age
6. Participant must have adequate organ function, defined as follows: System Hematologic*: Absolute neutrophil count (ANC):≥1.5 X 109/L, Hemoglobin: ≥8.0 g/dL, Platelets: ≥75 x 109/L for subjects in whom <50% of bone marrow nucleated cells are plasma cells; otherwise platelet count >50 × 109/L, Calcium: corrected serum calcium <14 mg/dL (<3.5 mmol/L); or free ionized calcium <6.5 mg/dL (<1.6 mmol/L); System Hepatic: Total bilirubin: ≤1.5X ULN (Isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%), ALT ≤2.5 X ULN, AST ≤2.5 X ULN; System Renal: eGFRa: ≥30 mL/min/ 1.73 m2, Spot urine (albumin/creatinine ratios (spot urine) ACR: <500 mg/g (56 mg/mmol) or 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) <500 mg/g (56 mg/mmol) * Without growth factor support, blood transfusion or platelet stimulating agents for the past 14 days, excluding erythropoietin.
7. Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 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 woman of childbearing potential (WOCBP) 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, during the intervention period and for at least 4 months after the last dose of study intervention 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 intervention. A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention. In this case, 2 blood tests will be. The first pregnancy test must be performed within 10 to 14 days prior to the start of treatment and the second pregnancy test must be performed within 24 hours prior to the start of treatment. After, pregnancy testThe pregnancy tests must be negative throughout the study (every week for the first 4 weeks, after that, before to receive study treatments. A urine or blood test can be used during the rest of the study. A WOCBP must agree to use a highly effective method of contraception during the study and for 4 months after the last dose of belantamab mafodotin. 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 a nearly undetected pregnancy. Nonchildbearing potential is defined as follows (by other than medical reasons): ● ≥45 years of age and has not had menses for >1 year ● Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation ● Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.
8. Male participants: contraceptive use 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 during the intervention period and until 6 months after the last dose of Belantamab mafodotin 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 contraception/barrier as detailed below: Agree to use a male condom and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females). All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 (must be ≤ Grade 1 at the time of enrolment except for alopecia).
9. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent.

Exclusion criteria 26

1. Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell leukemia or active POEMS syndrome at the time of screening.
2. Participant who have had major surgery ≤ 4 weeks prior to initiating protocol therapy.
3. Participant who have current corneal epithelial disease except mild punctate keratopathy
4. Participant has peripheral neuropathy or neuropathic pain grade ≥2, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 (APPENDIX 4).
5. Participant is unable or unwilling to undergone antithrombotic prophylactic treatment
6. Participant evidence of cardiovascular risk including any of the following: ● Evidence of current clinically significant uncontrolled/untreated arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block. ● History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within three months of Screening. ● Class III or IV heart failure as defined by the New York Heart Association functional classification system [NYHA, 1994] ● Uncontrolled hypertension
7. Incidence of gastrointestinal disease that may significantly alter the absorption of Lenalidomide.
8. Participant must not have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal 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 otherwise meets entry criteria
9. Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect patient’s safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil inclusion criteria
10. Participant who use contact lenses while participating in this study, except if contact lenses are removed during participation in the study
11. Participant who have had plasmapheresis within 7 days prior to first dose of study treatment.
12. Participant has malignancies other than disease under study, except for any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the principal investigators, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy. Participants with curatively treated non-melanoma skin cancer may be enrolled.
13. Evidence of active mucosal or internal bleeding.
14. Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form.
15. Uncontrolled endocrine diseases (i.e. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months).
16. Patients with acute diffuse infiltrative pulmonary disease and/or pericardial disease.
17. Patients with severe chronic obstructive pulmonary disease (COPD) or asthma with forced expiratory volume in the first minute (FEV1) less than 50%.
18. The subject is seropositive for human immunodeficiency virus (HIV) or presence of active hepatitis B infection (documented by a positive test for hepatitis B surface antigen [HBsAg], or hepatitis C (documented by Positive hepatitis C antibody test result or positive quantification of HCV RNA). Note: presence of Hep B surface antibody (HBsAb) indicating previous vaccination will not exclude a participant. Presence of HbcAb with negative hepatitis B PCR will not exclude and then, appropriate prophylaxis should be administered to avoid virus reactivation. If patients with HbcAb with negative hep B PCR included, it is necessary to do HBV- DNA testing prior to the start of study treatment and subsequently every 3 months, or if LFT elevations requiring increased monitoring or stopping criteria occur, or for any clinical suspicion of hepatitis reactivation Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Note: Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.
19. Participant has meningeal involvement of multiple myeloma.
20. Pregnant or breastfeeding females.
21. Participant is simultaneously enrolled in other interventional clinical trials.
22. Participant must have used an investigational drug within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug.
23. Participant has used of any anti-myeloma drug therapy, except for steroid pulses in case of emergency (40 mg of dexamethasone for 4 days), the administration of bisphosphonates or antialgic radiotherapy or due to the presence of plasmacytomas requiring some emergency.
24. Participant who has received prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs. Note: Monoclonal antibodies used for serious conditions unrelated to MM, such as COVID, may be permitted but need to be discussed with the MD.
25. Participant has a known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, or any other components of the study treatment.
26. Active infection requiring treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. Number of participants with adverse events (AEs) during the induction therapy (six treatment cycles)
2. Change from Baseline in hematology parameters: absolute white blood cell count (WBC), basophils, eosinophils, lymphocytes, monocytes, platelet count, and neutrophils (Giga cells per liter) the induction therapy (six treatment cycles).
3. Change from Baseline in hematology parameters: Red Blood Cell (RBC) count and reticulocyte count (Trillion cells per liter) the induction therapy (six treatment cycles)
4. Change from Baseline in clinical chemistry parameters: Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine kinase (CK), Gamma Glutamyl Transferase (GGT), and lactate dehydrogenase (LDH)
5. Change from Baseline in clinical chemistry parameters: Calcium, chloride, glucose, potassium, sodium, magnesium, blood urea nitrogen (BUN), and phosphorous (Millimoles per Liter) during the induction therapy (six treatment cycles)
6. Change from Baseline in clinical chemistry parameters: Creatinine, direct bilirubin, total bilirubin, uric acid (Micromoles per liter) at baseline and during the induction therapy (six treatment cycles)
7. Number of participants with abnormal ocular findings during the induction therapy (six treatment cycles)
8. Number of participants with symptomatic adverse effects measured by Ocular Surface Disease Index (OSDI) during the induction therapy (six treatment cycles).

Secondary endpoints 9

1. Complete Response Rate (CRR), defined as the percentage of participants with a confirmed complete response (CR) or better (stringent complete response (CR, sCR)).
2. Progression-free survival (PFS). PFS, defined as the time from the date of study inclusion until the earliest date of documented disease progression (according to International Myeloma Working Group [IMWG] Response Criteria, APPENDIX 7) or death due to any cause
3. PFS2, defined as time from inclusion to disease progression after initiation of new anti-cancer therapy or death from any cause, whichever is earlier. If disease progression after new anti-cancer therapy cannot be measured, a PFS event is defined as the date of discontinuation of new anti-cancer therapy, or death from any cause, whichever is earlier.
4. Overall survival (OS). OS, defined as the time from study inclusion until death due to any cause
5. Overall response rate (ORR). ORR, defined as the percentage of participants with a confirmed partial response (PR) or better per IMWG
6. Duration of response (DoR). DoR, defined as the time from first documented evidence of PR or better until progressive disease (PD) per IMWG or death due to PD among participants who achieve confirmed PR or better
7. Time to response (TTR). TTR, defined as the time between the date of inclusion and the first documented evidence of response (PR or better) among participants who achieve confirmed PR or better.
8. Time to progression (TTP). TTP, defined as the time from the date of study inclusion until the earliest date of documented PD (per IMWG Response Criteria) or death due to PD
9. Rate of Minimal Residual Disease (MRD). MRD negativity rate, defined as; the percentage of participants who are MRD negative by Next generation flow cytometry (NGF) method.

Investigational products

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

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Pethema

Sponsor organisation

Fundacion Pethema

Address

Calle De Santa Balbina 2 Oficinas 3 4 5

City

Madrid

Postcode

28023

Country

Spain

Scientific contact point

Organisation

Fundacion Pethema

Contact name

A person designed by the Sponsor

Public contact point

Organisation

Fundacion Pethema

Contact name

A person designed by the Sponsor

Third parties 2

Locations

1 EU/EEA country · 14 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 9 files

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

Application history

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