Issued: 9 December 2024, London
UK
Blenrep
shows significant
overall survival benefit, reducing the risk of death by 42% in
multiple myeloma at or after first relapse
· DREAMM-7 trial shows sustained overall survival benefit for
Blenrep (belantamab
mafodotin) combination versus daratumumab
combination; benefit seen early and
maintained through follow-up
· Data build on findings from DREAMM-7 and DREAMM-8 and support
the potential for Blenrep
combinations to become standard of care
· Blenrep
combinations are under regulatory review in seven
major markets
GSK plc (LSE/NYSE: GSK) today
announced statistically significant and clinically meaningful
overall survival (OS) results from a planned interim analysis
of the DREAMM-7 trial evaluating
Blenrep (belantamab mafodotin)
in combination with bortezomib plus dexamethasone (BVd) versus
daratumumab in combination with bortezomib plus dexamethasone
(DVd) as a second line or later treatment
for relapsed or refractory multiple myeloma. These data were
featured today in an oral presentation at the 66th
American Society of Hematology (ASH) Annual Meeting and
Exposition.
The OS findings from DREAMM-7 build
on previous data from the
DREAMM-7[1] and
DREAMM-8[2] trials, which showed a statistically significant and
clinically meaningful improvement in progression-free survival
(PFS) for both belantamab mafodotin-based combinations versus
standard of care comparators.
Hesham Abdullah, Senior Vice President, Global Head Oncology,
R&D, GSK, said: "The compelling
overall survival data from the DREAMM-7 trial establish the
potential of Blenrep in
combination to significantly extend the lives of patients with
multiple myeloma at or after first relapse. This represents an
important advancement that could redefine the treatment of relapsed
or refractory multiple myeloma."
With a median follow up of 39.4
months, the analysis presented today shows a statistically
significant 42% reduction in the risk of death among patients
receiving the belantamab mafodotin combination (n=243) versus the
daratumumab-based comparator (n=251) (HR 0.58; 95% CI: 0.43-0.79;
p=0.00023). Although the median overall
survival (mOS) was not reached in either arm of the study, the
projected mOS for BVd is 84 months compared to 51 months for
DVd.[3]
The three-year OS rate was 74% in
the belantamab mafodotin combination arm and 60% in the daratumumab
combination arm. The survival benefit favouring BVd was seen as
early as four months and was sustained over time as illustrated by
the separation of the lines in the Kaplan-Meier curve shown
here.
BVd, belantamab mafodotin,
bortezomib, and dexamethasone; DVd, daratumumab, bortezomib, and
dexamethasone; HR, hazard ratio; ITT, intention to treat; NR, not
reached; OS, overall survival; R-ISS, Revised International Staging
System.
a Two patients in the ITT population were randomised, not
treated, rescreened, and rerandomised. They are counted as 4 unique
patients in this output.
b CIs were estimated using the Brookmeyer-Crowley
method.
c HRs were estimated using a Cox proportional hazards model
stratified by the number of lines of prior therapy (1 vs 2 or 3 vs
≥4), prior bortezomib (no vs yes), and R-ISS stage at screening (I
vs II or III), with a covariate of treatment.
d P value is from a
1-sided stratified log-rank test. At 171 actual events (48.2% OS
information fraction), OS was declared significant if the
P value was
<.00112.
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: "The totality of
evidence from DREAMM-7 represents a potential paradigm shift for
multiple myeloma patients who have experienced a relapse or become
refractory to initial treatment. The OS results shown with the
belantamab mafodotin combination in DREAMM-7 further cement the
potential of this regimen to prolong the lives of patients with
relapsed or refractory multiple myeloma compared to a standard of
care daratumumab combination."
The belantamab mafodotin combination
also showed statistically significant superiority on the key
secondary endpoint of minimal residual disease (MRD) negativity (no
detectable cancer cells) compared to the daratumumab combination.
The greater than 2.5-fold improvement in the rate of MRD negativity
seen at the time of the primary analysis for patients who received
BVd can now be declared as statistically significant (p<0.00001)
after the positive OS readout based on the predefined testing
procedure. This further underscores the transformative potential of
this belantamab mafodotin combination for multiple myeloma patients
at or after their first relapse.
In addition to OS and MRD
negativity, the belantamab mafodotin combination resulted in
clinically meaningful improvements in all key secondary efficacy
endpoints compared to the daratumumab combination, including
duration of response (DOR) and progression-free survival 2 (PFS 2).
The results indicate deeper and more durable responses among
patients treated with BVd compared to DVd.
The safety and tolerability of the
belantamab mafodotin regimen were consistent with the primary
analysis and known safety profile of the individual agents. Grade 3
or higher adverse events of clinical interest in the belantamab
mafodotin combination and daratumumab combination arms,
respectively included thrombocytopenia (56% versus 35%; 34 versus
25 patients/100 person-years); anaemia (9% versus 10%;
exposure-adjusted rate [per 100 person-years] not reported); and
neutropenia (14% versus 10%; 8 versus 7 patients/100
person-years).
Eye-related side effects, a known
risk of treatment with belantamab mafodotin, were generally
manageable and resolvable with dose modification, and led to a low
(10%) treatment discontinuation rate.
Full data summaries for OS and other
key secondary endpoints are shown below.
|
Key
Secondary Endpoints
|
|
Endpoint
|
belantamab mafodotin +
bortezomib + dexamethasone (BVd)
n=243
|
daratumumab +
bortezomib + dexamethasone (DVd)
n=251
|
|
OS (overall survival), HR (95%
CI)
P-value1
|
0.58
(0.43-0.79)
|
|
p=0.00023
|
|
OS, median (95% CI),
months
|
NR
(NR-NR)
|
NR
(41.0-NR)
|
|
OS rate at 24 months, % (95%
CI)
|
79%
(73-84)
|
67%
(61-73)
|
|
OS rate at 36 months, % (95%
CI)
|
74%
(68-79)
|
60%
(54-66)
|
|
MRD (minimal residual disease)
negativity rate for patients with CR or better, % (95%
CI)
|
25.1%
(19.8-31.0)
|
10.4%
(6.9-14.8)
|
|
ORR (overall response rate), % (95%
CI)
|
83.1%
(77.8-87.6)
|
71.3%
(65.3-76.8)
|
|
CR (complete response), or better, %
(95% CI)
|
35.8%
(29.8-42.2)
|
17.5%
(13.0-22.8)
|
|
VGPR (very good partial response),
or better, % (95% CI)
|
66.3%
(59.9-72.2)
|
46.2%
(39.9-52.6)
|
|
Median DOR (duration of response)
(95% CI), months
|
40.8
(30.5-NR)
|
17.8
(13.8-23.6)
|
|
Median PFS 2 (progression-free
survival 2), months
HR
|
NR
(45.6-NR)
|
33.4
(26.7-44.9)
|
|
0.59
(0.45-0.77)
|
1One-sided p-value based on stratified log-rank
test.
In 2024, regulatory filings for
belantamab mafodotin combinations for the treatment of relapsed or
refractory multiple myeloma based on the results of the DREAMM-7
and DREAMM-8 trials have been accepted in the
US[4],
European Union[5],
Japan[6] (with
priority review), China (for DREAMM-7 only,
with priority review;
Breakthrough Therapy Designation[7] also granted), United Kingdom, Canada and Switzerland (with
priority review for DREAMM-8).
About the DREAMM clinical development
programme
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. In addition to DREAMM-7 and
DREAMM-8, a phase III study in newly diagnosed transplant
ineligible multiple myeloma, DREAMM-10, is expected to be initiated
by the end 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 plus dexamethasone
(BVd) compared to a combination of daratumumab
and bortezomib plus dexamethasone (DVd) 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 BVd or DVd. 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, duration of response (DOR), and minimal residual disease (MRD)
negativity rate as assessed by next-generation sequencing. Other
secondary endpoints include overall response rate (ORR), safety,
and patient reported and quality of life outcomes.
Results from DREAMM-7 were
first
presented1 at the American
Society of Clinical Oncology (ASCO) Plenary Series in February
2024, shared in an encore presentation at the 2024 ASCO Annual
Meeting, and published in the New England Journal of
Medicine.
About multiple myeloma
Multiple myeloma is the third most
common blood cancer globally and is generally considered treatable
but not curable.[8],[9] There are approximately more than 180,000
new cases of multiple myeloma diagnosed globally each
year.[10] Research into new therapies is
needed as multiple myeloma commonly becomes refractory to available
treatments.[11] Many patients with multiple
myeloma, including approximately 65% in the US, are treated in a
community cancer setting, leaving an urgent need for new, effective
therapies with manageable side effects that can be administered
outside of an academic centre.[12],[13],[14]
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.
Blenrep is approved as
monotherapy in Hong Kong. Refer to the local Summary of Product
Characteristics for a full list of adverse events and complete
important safety information.
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
enquiries
|
|
|
|
|
Media:
|
Tim Foley
|
+44 (0) 20 8047 5502
|
(London)
|
|
|
Madison Goring
|
+44 (0) 20 8047 5502
|
(London)
|
|
|
Kathleen Quinn
|
+1 202 603 5003
|
(Washington DC)
|
|
|
Lyndsay Meyer
|
+1 202 302 4595
|
(Washington DC)
|
|
|
|
|
|
|
Investor Relations:
|
Annabel Brownrigg-Gleeson
|
+44 (0) 7901 101944
|
(London)
|
|
|
James Dodwell
|
+44 (0) 7881 269066
|
(London)
|
|
|
Mick Readey
|
+44 (0) 7990 339653
|
(London)
|
|
|
Camilla Campbell
|
+44 (0) 7803 050238
|
(London)
|
|
|
Steph Mountifield
|
+44 (0) 7796 707505
|
(London)
|
|
|
Jeff McLaughlin
|
+1 215 751 7002
|
(Philadelphia)
|
|
|
Frannie DeFranco
|
+1 215 751 4855
|
(Philadelphia)
|
|
|
|
|
|
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 GSK's Annual Report on Form 20-F for 2023, and
GSK's Q3 Results for 2024.
Registered in England & Wales:
No. 3888792
Registered Office:
79 New Oxford Street
London
WC1A 1DG