Issued: 5 February 2024, London
UK
DREAMM-7 phase III trial shows Blenrep combination nearly tripled
median progression-free survival versus standard of care
combination in patients with relapsed/refractory multiple
myeloma
· 59% reduction in risk of disease progression or death observed
in patients with Blenrep
combination versus standard of care daratumumab
combination
· 36.6 months of median progression-free survival observed with
Blenrep combination versus
13.4 months in daratumumab combination
· Strong, clinically meaningful trend in overall survival
favouring Blenrep
combination was observed with 43% reduction in risk of
death
GSK plc (LSE/NYSE: GSK) today
announced results from an interim analysis of the DREAMM-7 phase
III head-to-head trial evaluating Blenrep (belantamab mafodotin)
combined with bortezomib plus dexamethasone (BorDex) versus
daratumumab plus BorDex in second-line and later treatment of
relapsed or refractory multiple myeloma. These data will be
presented at the American Society of Clinical Oncology (ASCO)
Plenary Series on 6 February 2024.
In the primary endpoint of
progression-free survival (PFS), a statistically significant and
clinically meaningful improvement was observed with the belantamab
mafodotin combination (n=243), showing a 59% reduction in the risk
of disease progression or death (hazard ratio [HR]: 0.41 [95%
confidence interval (CI): 0.31-0.53], p-value<0.00001) compared
to the daratumumab combination (n=251). With a median follow-up of
28.2 months, the median PFS was 36.6 months (95% CI: 28.4-not
reached [NR]) with the belantamab mafodotin combination compared to
13.4 months (11.1-17.5) in the daratumumab combination. The PFS
effect was observed across all prespecified subgroups, including
those who were refractory to lenalidomide and those with high-risk
cytogenetics. The safety and tolerability
profile of the belantamab mafodotin
combination was consistent with the known profile of the individual
agents.
Hesham Abdullah, Senior Vice President, Global Head Oncology,
R&D, GSK, said: "The substantial
progression-free survival benefit and strong overall survival trend
compared to a daratumumab standard of care combination reinforce
our belief in the potential for belantamab mafodotin used in
combination to redefine the treatment of multiple myeloma at or
after first relapse. We plan on sharing these results with health
authorities worldwide."
The belantamab mafodotin combination
also resulted in clinically meaningful improvements in all
secondary efficacy endpoints including a doubling of complete
response rate (stringent complete response plus complete response),
minimal residual disease (MRD) negativity rate and median duration
of response (DOR). A strong and clinically meaningful overall
survival (OS) trend was observed at the interim analysis, with a
43% reduction in the risk of death (HR: 0.57 [95% CI: 0.40-0.80],
p-value=0.00049), which has not yet reached the interim criteria
for statistical significance of OS. OS follow-up continues and
further analyses are planned.
María-Victoria Mateos, MD, PhD, Head of Myeloma and Clinical
Trials Unit, Haematology Department and Professor of Medicine at
the University of Salamanca, Spain, and DREAMM-7 principal
investigator, said: "These results
from DREAMM-7 show how belantamab mafodotin in combination with
BorDex represents a significant improvement over the
daratumumab-based regimen in a second-line multiple myeloma
treatment setting. Anti-BCMA therapies are helping to improve
outcomes for patients with multiple myeloma, and having an
off-the-shelf option, like belantamab mafodotin, that can be
administered in a community oncology treatment centre where the
majority of patients are treated has the potential to transform the
way we treat myeloma at or after first relapse."
Key secondary endpoint summaries are
listed below.
Key
Secondary Endpoints
|
Endpoint
|
belantamab mafodotin + BorDex
(n= 243)
|
daratumumab + BorDex
(n=251)
|
ORR (overall response rate) (95%
CI)
|
82.7% (77.4-87.3)
|
71.3% (65.3-76.8)
|
sCR (stringent complete
response)
|
14.0%
|
5.2%
|
CR (complete response)
|
20.6%
|
12.0%
|
Very good partial
response
|
31.3%
|
29.1%
|
Partial response
|
16.9%
|
25.1%
|
MRD negativity rate* (95%
CI)
|
24.7 (19.4, 30.6)
|
9.6 (6.2, 13.9)
|
P-value
|
p<0.00001#
|
Median DOR (95% CI)**
|
35.6 months (30.5-NR)
|
17.8 months (13.8-23.6)
|
Overall survival
|
HR (95% CI)
P-value ***
|
0.57
(0.40-0.80) p=0.00049***
|
* Measured in patients
with a sCR or CR.
** An Intent-to-treat restricted
mean DOR (RMDoR) analysis comparing DOR between arms showed a
statistically significant benefit in favour of the belantamab
mafodotin combination (p < 0.00001).
*** Has not yet reached criteria for
statistical significance (p ≤ 0.00037) of OS at this interim.
Follow-up for OS is ongoing.
#Nominal p-value
Grade 3 or higher non-ocular adverse
events of clinical interest in the belantamab mafodotin combination
and daratumumab combination arms, respectively, included
thrombocytopenia (55% and 35%; exposure-adjusted event rate: 40 and
29, per 100 person-years), neutropenia (12% and 6%), pneumonia (12%
and 4%; exposure-adjusted event rate: 8 and 3, per 100
person-years), and anaemia (8% and 10%).
Eye-related side effects, a known
risk of treatment with belantamab mafodotin, were generally
reversible, manageable with dose modification, and led to low (9%)
treatment discontinuations. Grade 3 or
higher ocular adverse events occurred in 34% of patients receiving
the belantamab mafodotin combination and primarily included blurred
vision (22%), dry eye (7%), eye irritation (5%), and visual
impairment (5%). Eighty-two patients (34%) with a best
corrected visual acuity (BCVA) score of 20/25 or better in at least
one eye at baseline had a worsening in both eyes to 20/50 or worse.
Almost all these patients' events (98%) had resolved at the time of
this analysis. The median time to resolution was 22
days.
Global health status quality of life
(QOL) as measured by the EORTC-QLQ-C30 indicated no difference in
global QOL between different treatment arms over time.
The DREAMM (DRiving Excellence in
Approaches to Multiple Myeloma) clinical development programme
continues to evaluate the potential of belantamab mafodotin in
early lines of treatment and in combination with novel therapies
and standard of care treatments. This includes the ongoing phase
III DREAMM-8 trial evaluating belantamab mafodotin in combination
with pomalidomide and dexamethasone versus bortezomib in
combination with pomalidomide and dexamethasone. DREAMM-8 data are
expected in the second half of 2024.
About DREAMM-7
The DREAMM-7 phase III clinical
trial is a multicentre, open-label,
randomised trial evaluating the efficacy
and safety of belantamab mafodotin in combination with
bortezomib and dexamethasone (BorDex)
compared to a combination of daratumumab and BorDex in patients
with relapsed/refractory multiple myeloma who previously were
treated with at least one prior line of multiple myeloma
therapy, with documented disease
progression during or after their most recent therapy.
A total of 494 participants were
randomised at a 1:1 ratio to receive either belantamab mafodotin in
combination with BorDex or a combination of daratumumab and BorDex.
Belantamab mafodotin was scheduled to be dosed at 2.5mg/kg
intravenously every three weeks.
The primary endpoint is PFS as per
an independent review committee. The key secondary endpoints
include OS, DOR, and MRD negativity rate as assessed by
next-generation sequencing.
About multiple myeloma
Multiple myeloma is the third most
common blood cancer globally and is generally considered treatable
but not curable.1,2 There are approximately 176,000 new
cases of multiple myeloma diagnosed globally each year.3
Research into new therapies is needed as multiple myeloma commonly
becomes refractory to available treatments.4
About Blenrep
Blenrep is an antibody-drug
conjugate comprising a humanised B-cell maturation antigen
monoclonal antibody conjugated to the cytotoxic agent auristatin F
via a non-cleavable linker. The drug linker technology is licensed
from Seagen Inc.; the monoclonal antibody is produced using
POTELLIGENT Technology licensed from BioWa Inc., a member of the
Kyowa Kirin Group.
Refer to the Blenrep
EMA Reference
Information (https://www.ema.europa.eu/en/medicines/human/EPAR/blenrep)
for a full list of adverse events and the complete important safety
information in the EU.
GSK
in oncology
Oncology is an emerging therapeutic
area for GSK where we are committed to maximising patient survival
with a current focus on haematologic malignancies, gynaecologic
cancers and other solid tumours through breakthroughs in
immuno-oncology and tumour-cell targeting therapies.
About GSK
GSK is a global biopharma company
with a purpose to unite science, technology, and talent to get
ahead of disease together. Find out more at gsk.com.
GSK
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Cautionary statement regarding forward-looking
statements
GSK cautions
investors that any forward-looking statements or projections made
by GSK, including those made in this announcement, are subject to
risks and uncertainties that may cause actual results to differ
materially from those projected. Such factors include, but are not
limited to, those described under Item 3.D "Risk factors" in the
company's Annual Report on Form 20-F for 2022, and Q4 Results for
2023.
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References
1 Sung H, Ferlay J, Siegel R, et al. Global Cancer Statistics
2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for
36 Cancers in 185 Countries. CA
Cancer J Clin. 2021;71(3):209-249.
doi:10.3322/caac.21660.
2 Kazandjian D. Multiple myeloma
epidemiology and survival: A unique malignancy. Semin Oncol.
2016;43(6):676-681.
doi:10.1053/j.seminoncol.2016.11.004.
3 Multiple Myeloma: Statistics. Cancer.net. Published February
2022.
https://www.cancer.net/cancer-types/multiple-myeloma/statistics#:~:text=This%20year%2C%20an%20estimated%2034%2C470,with%20multiple%20myeloma%20in%202020.
Accessed 19 October 2023.
4 Nooka AK, Kastritis E, Dimopoulos MA.
Treatment options for relapsed and refractory multiple myeloma.
Blood.
2015;125(20).