Study to Investigate Alternative Dosing Regimens of Belantamab Mafodotin in Participants with Relapsed or Refractory Multiple Myeloma (DREAMM14)

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

15 Mar 2022 → 10 Feb 2026

Decision date (initial)

2024-03-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

GSK

External identifiers

EU CT number

2023-508213-16-00

EudraCT number

2021-004151-16

ClinicalTrials.gov

NCT05064358

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

To examine the corneal events associated with single-agent belantamab mafodotin using alternative dosing regimens in participants with RRMM in Arms B to D compared to Arm A

Secondary objectives 5

1. To further evaluate the corneal safety and tolerability of single-agent belantamab mafodotin in all arms
2. To evaluate the efficacy of single-agent belantamab mafodotin in all arms
3. To evaluate the overall safety and tolerability of single-agent belantamab mafodotin in all arms
4. To assess the pharmacokinetics of single-agent belantamab mafodotin in all arms
5. To assess anti-drug antibodies against single-agent belantamab mafodotin in all arms

Conditions and MedDRA coding

Multiple Myeloma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participant must be 18 years of age inclusive at the time of signing the Informed Consent Form (ICF).
2. Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
3. "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)."
4. "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)."
5. "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. "
6. "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. "
7. Life expectancy of at least 6 months, in the opinion of the investigator.
8. "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). "
9. 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.
10. Participant meets country-specific inclusion criteria described in Section 10.7, if applicable.

Exclusion criteria 20

1. 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.
2. Participant currently has corneal epithelial disease, except nonconfluent superficial punctate keratitis (SPK).
3. Participant has evidence of active mucosal or internal bleeding.
4. 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).
5. 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.
6. 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.
7. 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.
8. Participant is a pregnant or lactating female.
9. Participant has an active infection requiring antibiotic, antiviral, or antifungal therapy.
10. 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.
11. 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)
12. 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.
13. 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.
14. Participant has alanine aminotransferase (ALT) >2.5× upper limit of normal (ULN).
15. Participants has total bilirubin >1.5×ULN (isolated total bilirubin >1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
16. Participant has received systemic anti-myeloma therapy within ≤14 days or 5 half lives, whichever is shorter, before the first dose of study treatment.
17. Participant has received plasmapheresis 7 days before the first dose of study treatment.
18. 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.
19. Participant has received a prior allogenic stem cell transplant.
20. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence rate of Grade ≥2 corneal events according to the KVA scale

Secondary endpoints 20

1. Cumulative event rate of corneal events to Week 16 (KVA scale)
2. Incidence rate of corneal events by grade (KVA scale)
3. Exposure-adjusted incidence rate of corneal events by grade (KVA scale)
4. Median duration of dose delay
5. Percentage of participants requiring dose reductions, dose delays, and study treatment discontinuation due to corneal events (KVA scale)
6. Cumulative incidence of corneal events by grade (KVA scale)
7. Toxicity Index by assessment/visit
8. Percentage of time on study with corneal events (KVA scale)
9. Change in BCVA (ΔlogMAR)
10. ORR, defined as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR, and sCR)
11. Percentage of participants with a confirmed VGPR or better (i.e., VGPR, CR, and sCR)
12. TTR is 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)
13. DoR in responders, defined as the time from first documented evidence of PR or better until PD or death due to any cause
14. TTP, defined as the time from randomization until the earliest date of documented PD or death due to PD
15. PFS, defined as the time from randomization until the earliest date of documented PD or death due to any cause
16. OS, defined as the time from randomization until the date of death due to any cause
17. Instance of AEs (including ocular AEs) (CTCAE Version 5.0) and changes in laboratory parameters
18. Percentage of participants requiring dose reductions, dose delays, and study treatment discontinuation due to any AEs (CTCAE Version 5.0)
19. Plasma belantamab mafodotin pharmacokinetic parameters, as data permit
20. Incidence and titers of ADAs against belantamab mafodotin at each ADA time point

Investigational products

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

Test 1

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 Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 19

Locations

7 EU/EEA countries · 19 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 140 files

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

Application history

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