DREAMM 8: Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04484623
• Collaborator: (none)
• Enrollment: 450
• Locations: 132
• Arms: 2
• Anticipated Duration (Months): 90
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone (Arm A) compared with that of combination of pomalidomide, bortezomib and dexamethasone (Arm B) in participants with relapsed/refractory multiple myeloma (RRMM).

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Belantamab mafodotin; Drug: Pomalidomide; Drug: Dexamethasone; Drug: Bortezomib	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 450 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicenter, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Pomalidomide and Dexamethasone (B-Pd) Versus Pomalidomide Plus Bortezomib and Dexamethasone (PVd) in Participants With Relapsed/Refractory Multiple Myeloma (DREAMM 8)
• Actual Study Start Date: Oct 1, 2020
• Anticipated Primary Completion Date: Mar 31, 2023
• Anticipated Study Completion Date: Mar 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Belantamab mafodotin plus Pomalidomide and Dexamethasone	Drug: Belantamab mafodotin; Humanized anti-B-cell maturation antigen (BCMA) antibody/drug conjugate will be administered.; Drug: Pomalidomide; Immunomodulatory imide drug (IMiD) will be administered.; Drug: Dexamethasone; Synthetic glucocorticoid with anti-tumor activity will be administered.
Experimental: Arm B: Bortezomib plus Pomalidomide and Dexamethasone	Drug: Pomalidomide; Immunomodulatory imide drug (IMiD) will be administered.; Drug: Dexamethasone; Synthetic glucocorticoid with anti-tumor activity will be administered.; Drug: Bortezomib; Proteasome Inhibitor will be administered.

Outcome Measures

Primary Outcome Measures

1. Progression-free survival (PFS) [Up to 84 months]

   PFS will be defined as the time from start of study treatment to the first documented disease progression or death due to any cause, whichever occurs first.

Secondary Outcome Measures

1. Minimal residual disease (MRD) negativity rate [Up to 84 months]

   MRD negativity rate will be defined as the percentage of participants who are MRD negative by next-generation sequencing.

2. Overall response rate (ORR) [Up to 84 months]

   ORR will be defined as the percentage of participants with a confirmed partial response or better.

3. Complete response rate (CRR) [Up to 84 months]

   CRR will be defined as the percentage of participants with a confirmed complete response or better.

4. Very good partial response (VGPR) or better rate [Up to 84 months]

   VGPR will be the defined as the percentage of participants with a confirmed VGPR or better.

5. Duration of response (DoR) [Up to 84 months]

   DoR will be defined as the time from first documented evidence of partial response or better to date of first documented progression or death, whichever occurs first.

6. Time to best response (TTBR) [Up to 84 months]

   TTBR will be defined as the time from the start of study treatment to the first documented evidence of best response among participants who achieve partial response or better.

7. Time to response (TTR) [Up to 84 months]

   TTR will be defined as the time from the start of study treatment to the first documented evidence of response among participants who achieve partial response or better.

8. Time to progression (TTP) [Up to 84 months]

   TTP will be defined as the time from the start of study treatment until the first documented date of disease progression or death, whichever occurs first.

9. Overall survival (OS) [Up to 84 months]

   OS will be defined as the time from randomization to death due to any cause.

10. Progression-free survival on subsequent line of therapy (PFS2) [Up to 84 months]

    PFS2 will be defined as the time from start of study treatment to disease progression after initiation of new anti-cancer therapy or death from any cause, whichever occurs first.

11. Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Up to 84 months]

12. Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters [Up to 84 months]

13. Number of participants with abnormal ocular findings on ophthalmic examination [Up to 84 months]

14. Plasma concentrations of belantamab mafodotin at indicated time points [Up to 84 months]

15. Plasma concentrations of total monoclonal antibody (mAb) at indicated time points [Up to 84 months]

16. Plasma concentrations of monomethyl auristatin-F with a cysteine linker (cys-mcMMAF) at indicated time points [Up to 84 months]

17. Maximum observed concentration (Cmax) for pomalidomide [Up to 24 hours]

18. Time of Cmax (Tmax) for pomalidomide [Up to 24 hours]

19. Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC[0-t]) for pomalidomide [Up to 24 hours]

20. Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin [Up to 84 months]

21. Titers of ADAs against belantamab mafodotin [Up to 84 months]

22. Change from Baseline in symptoms as measured by patient-reported outcome version of the common terminology criteria for adverse events (PRO-CTCAE) [Baseline and up to 84 months]

    PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trials using a PRO-CTCAE score. The PRO-CTCAE includes an item library of 124 items representing 78 symptomatic toxicities drawn from the CTCAE.

23. Change from Baseline in impacts as measured by PRO-CTCAE [Baseline and up to 84 months]

    PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trial. Impacts of the side effects will be assessed using PRO-CTCAE score.

24. Change from Baseline in health related quality of life (HRQoL) as measured by European Organization for Research and Treatment of Cancer Quality of life Questionnaire 30-item core module (EORTC QLQ-C30) [Baseline and up to 84 months]

    EORTC Quality of Life questionnaire QLQ-C30 on a scale of 0-100. Lower scores correlate with worse quality of life and higher scores correlate with better quality of life.

25. Change from Baseline in HRQoL as measured by EORTC item library 52 (IL52) [Baseline and up to 84 months]

    EORTC QLQ- 20-item Multiple Myeloma Module (MY20) questionnaire will be referred to as the EORTC IL52. Only disease symptoms domain will be assessed. A high score represents a high level of symptoms or problems.

26. Change from Baseline in HRQoL as measured by EORTC QLQ-20-item Multiple Myeloma Module (MY20) [Baseline and up to 84 months]

    EORTC QLQ-MY20 is a questionnaire which will evaluate disease symptoms. In EORTC QLQ-MY20, domain scores will be averaged and will be transformed linearly to a score ranging from 0 to 100. Higher score represents high level of symptomatology or problems.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Capable of giving signed informed consent.

• Male or female, 18 years or older.

• Have a confirmed diagnosis of multiple myeloma (MM) as defined by the International Myeloma Working Group (IMWG) criteria.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

• 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 therapy.

• 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) (≥5.0 g/liter [L]), or

3. Serum free light chain (FLC) assay: involved FLC level ≥10 mg/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.

• Have undergone autologous stem cell transplant (ASCT) or are considered 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

• 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.

• Adequate organ system functions as mentioned in the protocol.

• Male and female participants agree to abide by protocol-defined contraceptive requirements.

Exclusion Criteria:

• Active plasma cell leukemia, symptomatic amyloidosis or active polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, and skin changes (POEMS) syndrome at the time of screening.

• Prior allogeneic SCT.

• 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.

• Plasmapheresis within 7 days prior to the first dose of study drug.

• Received prior treatment with or intolerant to pomalidomide.

• Received prior Beta cell maturation antigen (BCMA) targeted therapy.

• 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).

• 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.

• Any major surgery within the last 4 weeks.

• 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.

• 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.

• Evidence of active mucosal or internal bleeding.

• Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice.

• Active infection requiring treatment.

• Known human immunodeficiency virus (HIV) infection, unless the participant can meet all of the following criteria: a. Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/milliliters (mL); b. Cluster of differentiation (CD)4+ T-cell (CD4+) counts >=350 cells/microliters c. No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the last 12 months.

• Participants with hepatitis B will be excluded unless the protocol-defined criteria are met.

• Positive hepatitis C antibody (Hep C Ab) test result or positive hepatitis C ribonucleic acid (Hep 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:

1. RNA test negative. b. Successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative hepatitis C virus (HCV) RNA test after a washout period of at least 4 weeks. - Intolerance or contraindications to anti-viral prophylaxis.

• Presence of active renal conditions (such as infection, severe renal impairment requiring dialysis or any other condition that could affect participant's safety).

• Ongoing Grade 2 peripheral neuropathy with pain within 14 days prior to randomization or ≥Grade 3 peripheral neuropathy.

• Active or history of venous and arterial thromboembolism within the past 3 months.

• Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis.

• Current corneal disease except for mild punctate keratopathy.

• 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.

• Pregnant or lactating female.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Tucson	Arizona	United States	85712
2	GSK Investigational Site	Denver	Colorado	United States	80218
3	GSK Investigational Site	Fort Myers	Florida	United States	33901
4	GSK Investigational Site	New Port Richey	Florida	United States	34655
5	GSK Investigational Site	Pembroke Pines	Florida	United States	33024
6	GSK Investigational Site	Boston	Massachusetts	United States	02215
7	GSK Investigational Site	Kansas City	Missouri	United States	64132
8	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15224
9	GSK Investigational Site	Nashville	Tennessee	United States	37203
10	GSK Investigational Site	Seattle	Washington	United States	98109
11	GSK Investigational Site	Spokane	Washington	United States	99202
12	GSK Investigational Site	Milwaukee	Wisconsin	United States	53226
13	GSK Investigational Site	Canberra	Australian Capital Territory	Australia	2605
14	GSK Investigational Site	Darlinghurst	New South Wales	Australia	2010
15	GSK Investigational Site	Gosford	New South Wales	Australia	2250
16	GSK Investigational Site	Port Macquarie	New South Wales	Australia	2444
17	GSK Investigational Site	Randwick	New South Wales	Australia	2031
18	GSK Investigational Site	Wollongong	New South Wales	Australia	2500
19	GSK Investigational Site	Benowa	Queensland	Australia	4217
20	GSK Investigational Site	South Brisbane	Queensland	Australia	4101
21	GSK Investigational Site	Adelaide	South Australia	Australia	5000
22	GSK Investigational Site	Fitzroy	Victoria	Australia	3065
23	GSK Investigational Site	Geelong	Victoria	Australia	3220
24	GSK Investigational Site	Heidelberg	Victoria	Australia	3084
25	GSK Investigational Site	Malvern	Victoria	Australia	3144
26	GSK Investigational Site	Nedlands	Western Australia	Australia	6009
27	GSK Investigational Site	Ottawa	Ontario	Canada	K1H 8L6
28	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2M9
29	GSK Investigational Site	Montreal		Canada	H2X 0A9
30	GSK Investigational Site	Brno		Czechia	625 00
31	GSK Investigational Site	Hradec Kralove		Czechia	500 05
32	GSK Investigational Site	Praha 2		Czechia	128 08
33	GSK Investigational Site	Dijon cedex		France	21079
34	GSK Investigational Site	Marseille Cedex 9		France	13273
35	GSK Investigational Site	Périgueux cedex		France	24019
36	GSK Investigational Site	Toulouse cedex 9		France	31059
37	GSK Investigational Site	Vandeouvre-les-Nancy		France	54500
38	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg	Germany	69120
39	GSK Investigational Site	Tuebingen	Baden-Wuerttemberg	Germany	72076
40	GSK Investigational Site	Wuerzburg	Bayern	Germany	97080
41	GSK Investigational Site	Mainz	Rheinland-Pfalz	Germany	55101
42	GSK Investigational Site	Leipzig	Sachsen	Germany	04103
43	GSK Investigational Site	Jena	Thueringen	Germany	07747
44	GSK Investigational Site	Berlin		Germany	12351
45	GSK Investigational Site	Hamburg		Germany	20246
46	GSK Investigational Site	Athens		Greece	10676
47	GSK Investigational Site	Athens		Greece	115 28
48	GSK Investigational Site	Athens		Greece	11525
49	GSK Investigational Site	Athens		Greece	11527
50	GSK Investigational Site	Ioannina		Greece	45 500
51	GSK Investigational Site	Larisa		Greece	41110
52	GSK Investigational Site	Rio/Patras		Greece	26504
53	GSK Investigational Site	Thessaloniki		Greece	546 36
54	GSK Investigational Site	Thessaloniki		Greece	57010
55	GSK Investigational Site	Ashdod		Israel	7747629
56	GSK Investigational Site	Beer-Sheva		Israel	84101
57	GSK Investigational Site	Haifa		Israel	31096
58	GSK Investigational Site	Jerusalem		Israel	91031
59	GSK Investigational Site	Jerusalem		Israel	91120
60	GSK Investigational Site	Kfar Saba		Israel	44281
61	GSK Investigational Site	Nahariya		Israel	22100
62	GSK Investigational Site	Petach Tikva		Israel	49100
63	GSK Investigational Site	Ramat Gan		Israel	52621
64	GSK Investigational Site	Tel Aviv		Israel	64239
65	GSK Investigational Site	Bologna	Emilia-Romagna	Italy	40138
66	GSK Investigational Site	Roma	Lazio	Italy	00161
67	GSK Investigational Site	Pavia	Lombardia	Italy	27100
68	GSK Investigational Site	San Giovanni Rotondo	Puglia	Italy	71013
69	GSK Investigational Site	Milano		Italy	20122
70	GSK Investigational Site	Ehime		Japan	790-8524
71	GSK Investigational Site	Fukushima		Japan	960-1295
72	GSK Investigational Site	Gunma		Japan	371-8511
73	GSK Investigational Site	Okayama		Japan	701-1192
74	GSK Investigational Site	Busan		Korea, Republic of	49241
75	GSK Investigational Site	Gyeonggi-do		Korea, Republic of	10408
76	GSK Investigational Site	Hwasun-gun, Jeollanam-do		Korea, Republic of	58128
77	GSK Investigational Site	Incheon		Korea, Republic of	405-760
78	GSK Investigational Site	Seoul		Korea, Republic of	03722
79	GSK Investigational Site	Seoul		Korea, Republic of	06351
80	GSK Investigational Site	Seoul		Korea, Republic of	06591
81	GSK Investigational Site	Seoul		Korea, Republic of	110-744
82	GSK Investigational Site	Ulsan		Korea, Republic of	44033
83	GSK Investigational Site	Auckland		New Zealand	2025
84	GSK Investigational Site	Auckland		New Zealand	622
85	GSK Investigational Site	Christchurch		New Zealand	8011
86	GSK Investigational Site	Dunedin		New Zealand	9001
87	GSK Investigational Site	Grafton, Auckland		New Zealand	1023
88	GSK Investigational Site	Hamilton		New Zealand	2001
89	GSK Investigational Site	Tauranga		New Zealand	3143
90	GSK Investigational Site	Bydgoszcz		Poland	85-168
91	GSK Investigational Site	Gdansk		Poland	80-214
92	GSK Investigational Site	Krakow		Poland	31-501
93	GSK Investigational Site	Lodz		Poland	93-513
94	GSK Investigational Site	Lublin		Poland	20-090
95	GSK Investigational Site	Wroclaw		Poland	50-367
96	GSK Investigational Site	Kaluga		Russian Federation	248007
97	GSK Investigational Site	Moscow		Russian Federation	125284
98	GSK Investigational Site	Moscow		Russian Federation	125284
99	GSK Investigational Site	Nizhniy Novgorod		Russian Federation	603126
100	GSK Investigational Site	Novosibirsk		Russian Federation	630087
101	GSK Investigational Site	Omsk		Russian Federation	644013
102	GSK Investigational Site	Saint Petersburg		Russian Federation	197341
103	GSK Investigational Site	Samara		Russian Federation	443099
104	GSK Investigational Site	Sochi		Russian Federation	354057
105	GSK Investigational Site	St'Petersburg		Russian Federation	191024
106	GSK Investigational Site	St. Petersburg		Russian Federation	197 089
107	GSK Investigational Site	Tula		Russian Federation	300053
108	GSK Investigational Site	Móstoles	Madrid	Spain	28933
109	GSK Investigational Site	Madrid	Navarra	Spain	28027
110	GSK Investigational Site	Badalona		Spain	08036
111	GSK Investigational Site	Barcelona		Spain	8035
112	GSK Investigational Site	Gijon		Spain	33204
113	GSK Investigational Site	Madrid		Spain	28006
114	GSK Investigational Site	Murcia		Spain	30008
115	GSK Investigational Site	Pamplona		Spain	31008
116	GSK Investigational Site	Pozuelo De Alarcón/Madrid		Spain	28223
117	GSK Investigational Site	Salamanca		Spain	37007
118	GSK Investigational Site	Sevilla		Spain	41013
119	GSK Investigational Site	Valencia		Spain	46026
120	GSK Investigational Site	Ankara		Turkey	06100
121	GSK Investigational Site	Ankara		Turkey	06560
122	GSK Investigational Site	Ankara		Turkey	6110
123	GSK Investigational Site	Istanbul		Turkey	34214
124	GSK Investigational Site	Izmir		Turkey	35100
125	GSK Investigational Site	Izmir		Turkey	35340
126	GSK Investigational Site	Kocaeli		Turkey	41400
127	GSK Investigational Site	Mersin		Turkey	33343
128	GSK Investigational Site	Samsun		Turkey	55139
129	GSK Investigational Site	Airdrie	Lanarkshire	United Kingdom	ML6 0JS
130	GSK Investigational Site	Stoke-on-Trent	Staffordshire	United Kingdom	ST4 6QG
131	GSK Investigational Site	London		United Kingdom	W12 0HS
132	GSK Investigational Site	Plymouth		United Kingdom	PL6 8D8

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT04484623
• Other Study ID Numbers: 207499
• First Posted: Jul 23, 2020
• Last Update Posted: Jul 5, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: Belantamab Mafodotin; Relapsed/Refractory Multiple Myeloma; Pomalidomide; Dexamethasone; Bortezomib
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Bortezomib; Pomalidomide

Study Results

No Results Posted as of Jul 5, 2022