Issued: 2 June 2024, London
UK
Blenrep
combination
reduced the risk of disease progression or death by nearly 50%
versus standard of care combination in relapsed/refractory multiple
myeloma
· DREAMM-8 phase III trial showed statistically significant and
clinically meaningful improvement in primary endpoint of
progression-free survival (PFS)
· Median PFS not yet reached at 21.8 months median follow-up
versus 12.7 months in bortezomib combination
· Second trial to show robust efficacy for a Blenrep combination versus a standard
of care in second line and later relapsed/refractory multiple
myeloma
· Results simultaneously published in the New England Journal of
Medicine
GSK plc (LSE/NYSE: GSK) today
announced positive results from an interim analysis of the DREAMM-8
phase III head-to-head trial evaluating Blenrep (belantamab mafodotin), in
combination with pomalidomide plus dexamethasone (PomDex), versus a
standard of care, bortezomib plus PomDex, as a second line and
later treatment for relapsed or refractory multiple myeloma. These
late-breaking data, being presented today at the 2024 American
Society of Clinical Oncology (ASCO) Annual Meeting (31 May - 4
June) in Chicago, IL, were featured in the official ASCO press
programme and simultaneously published in the New England Journal of
Medicine.
On the primary endpoint of
progression-free survival (PFS), a statistically significant and
clinically meaningful improvement (hazard ratio [HR]: 0.52 [95%
confidence interval (CI): 0.37-0.73], p-value<0.001) was
observed with the belantamab mafodotin combination (n=155) compared
to the bortezomib combination (n=147). At a median follow-up of
21.8 months, the median PFS was not yet reached (95% CI: 20.6-not
yet reached [NR]) with the belantamab mafodotin combination
compared to 12.7 months (95% CI: 9.1-18.5) in the bortezomib
combination. At the end of one year, 71% (95% CI: 63-78) of
patients in the belantamab mafodotin combination group compared to
51% (95% CI: 42-60) in the bortezomib combination group were alive
and had not progressed. A benefit for belantamab mafodotin plus
PomDex was observed across all pre-specified subgroups including
those with poor prognostic features, such as patients who
were refractory to lenalidomide and patients with
high-risk cytogenetics.
Hesham Abdullah, Senior Vice President, Global Head Oncology,
R&D, GSK, said: "With the robust
results from the DREAMM-8 phase III head-to-head trial, we now have
consistent data from two phase III trials supporting the potential
for Blenrep combinations
to redefine the treatment of multiple myeloma at or after first
relapse. This is exciting news given the high unmet need for new
and efficacious combinations once patients relapse or stop
responding to initial treatments. We continue to share data and
discuss our path forward with regulators."
A positive overall survival (OS)
trend was observed but not statistically significant (HR:
0.77 [95% CI: 0.53-1.14]) at the interim analysis. OS follow-up continues and further
analyses are planned. At the end of one year, 83% (95% CI: 76-88)
of patients were alive in the belantamab mafodotin combination
group versus 76% (95% CI: 68-82) in the bortezomib combination
group. The safety and tolerability profile of the belantamab
mafodotin combination was broadly consistent with the known profile
of the individual agents.
Suzanne Trudel, MD, Department of Medical Oncology and
Hematology, Princess Margaret Cancer Centre, University Health
Network, Toronto, Canada, said: "The
profound progression-free survival benefit seen in DREAMM-8
highlights the potential for belantamab mafodotin, when used with
pomalidomide and dexamethasone, to improve outcomes for patients
with relapsed/refractory multiple myeloma. This combination may
have potential to redefine treatment of multiple myeloma at or
after first relapse, a setting where patients may benefit from
novel therapies."
Similar to the results seen in the
DREAMM-7 phase III head-to-head trial, in DREAMM-8 the belantamab
mafodotin combination also resulted in clinically meaningful
improvements consistently across secondary efficacy endpoints,
showing that the belantamab mafodotin combination resulted in
deeper and more durable responses compared to the bortezomib
combination. Key improvements included rate of complete response
(CR) or better (more than twofold improvement); minimal residual
disease (MRD) negativity rate (nearly fivefold improvement); and
duration of response (median not yet reached with the belantamab
mafodotin combination versus 17.5 months with the bortezomib
combination).
Key and other secondary endpoint
summaries are listed below.
Key
and Other Secondary Endpoints
|
Endpoint
|
belantamab mafodotin +
pomalidomide and dexamethasone (BPd)
(n= 155)
|
pomalidomide + bortezomib and
dexamethasone (PVd)
(n=147)
|
ORR (overall response rate), % (95%
CI)
|
77%
(70.0-83.7)
|
72%
(64.1-79.2)
|
sCR (stringent complete response),
%
|
9%
|
3%
|
CR (complete response), %
|
31%
|
14%
|
VGPR (very good partial response),
%
|
24%
|
22%
|
PR (partial response), %
|
14%
|
34%
|
CR or better rate (sCR+CR),
% (95% CI)
|
40%
(32.2-48.2)
|
16%
(10.7-23.3)
|
VGPR or better rate
(sCR+CR+VGPR), %
(95% CI)
|
64%
(55.8-71.4)
|
38%
(30.2-46.5)
|
MRD negativity rate* % (95%
CI)
|
23.9%
(17.4-31.4)
|
4.8%
(1.9-9.6)
|
Duration of response (months),
median (95% CI)
|
NR
(24.9-NR)
|
17.5
months (12.1-26.4)
|
Overall Survival**
|
HR (95% CI)
|
0.77
(0.53-1.14)
|
* Measured in patients with a sCR or
CR.
** Follow-up for OS is
ongoing.
NR: Not yet reached.
Grade 3 or higher non-ocular adverse
events (AEs) of clinical interest in the belantamab mafodotin
combination versus bortezomib combination arms, respectively,
included neutropenia (57% versus 39%; 42 patients/100 person-years
in both arms); thrombocytopenia (38% versus 29%; 28 vs 31
patients/100 person-years); and pneumonia (17% versus 8%; 13 versus
8 patients/100 person-years).
Eye-related side effects, a known
risk of treatment with belantamab mafodotin, were generally
reversible, manageable with dose modifications, and led to low (9%)
treatment discontinuation rates. Grade 3 or
higher ocular adverse events occurred in 43% of patients receiving
the belantamab mafodotin combination (Grade 3: 42%; Grade 4: 1%).
Most commonly reported grade 3 or higher ocular symptoms included
blurred vision (Grade 3: 17%; Grade 4: 0), dry eye (Grade 3: 8%:
Grade 4: 0), and foreign body sensation in the eyes (Grade 3: 6%;
Grade 4: 0). Fifty-one patients (34%) with a best corrected
visual acuity (BCVA) of 20/25 or better in at least one eye at
baseline had a worsening in both eyes to 20/50 or worse. At the
time of this analysis, the first occurrence of such events had
improved in 92% of these patients, and resolved in 85%, with a
median time to resolution of 57 days (range: 14-451
days).
Global health status quality of life
(QOL), as measured by the EORTC-QLQ-C30 remained stable in both
treatment arms over time, suggesting that treatment did not lead to
any decline in overall health related QOL.
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. DREAMM-8 is the second phase III
head-to-head belantamab mafodotin combination trial in second line
and later treatment for multiple myeloma to report positive
results. Positive findings from DREAMM-7, a phase III head-to-head
trial evaluating belantamab mafodotin in combination with
bortezomib and dexamethasone (BorDex) versus daratumumab plus
BorDex in the same treatment setting, were
presented1
at the ASCO Plenary Series on 6 February 2024,
shared in an encore presentation at the 2024 ASCO Annual Meeting,
and published in the New England
Journal of Medicine.
About DREAMM-8
The DREAMM-8 phase III clinical
trial is a multicentre, open-label, randomised trial evaluating the
efficacy and safety of belantamab mafodotin in combination with
PomDex compared to a combination of bortezomib and PomDex in
patients with relapsed/refractory multiple myeloma previously
treated with at least one prior line of multiple myeloma therapy,
including a lenalidomide-containing regimen, and who have
documented disease progression during or after their most recent
therapy. Compared to the patient population studied in the DREAMM-7
trial, patients in DREAMM-8 were more heavily pre-treated in that
all had prior exposure to lenalidomide, 75% were refractory to
lenalidomide, 25% had prior daratumumab exposure and of those most
were daratumumab refractory.
A total of 302 participants were
randomised at a 1:1 ratio to receive either belantamab mafodotin
plus PomDex, or bortezomib plus PomDex.
The primary endpoint is PFS
as per an independent review committee. Key
secondary endpoints include OS, minimal residual disease negativity
as assessed by next-generation sequencing, and duration of
response. Other secondary endpoints include ORR, patient-reported
quality of life outcomes, adverse events, eye exam findings, and
laboratory investigations.
About multiple myeloma
Multiple myeloma is the third most
common blood cancer globally and is generally considered treatable
but not curable.2,3 There are approximately 176,000 new
cases of multiple myeloma diagnosed globally each year.4
Research into new therapies is needed as multiple myeloma commonly
becomes refractory to available treatments.5
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 UK
Summary of Product
Characteristics6 for a full list of adverse
events and the complete important safety information in the United
Kingdom.
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 GSK's
Annual Report on Form 20-F for 2023, and GSK's Q1 Results for
2024.
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References
1 GSK press release issued 05
February 2024. 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.
Available at:
https://www.gsk.com/en-gb/media/press-releases/dreamm-7-phase-iii-trial-shows-pfs-improvement-and-strong-os-trend-for-blenrep-combo-versus-soc-combo-in-multiple-myeloma/.
2 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.
3 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.
4 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.
5 Nooka AK, Kastritis E, Dimopoulos
MA. Treatment options for relapsed and refractory multiple myeloma.
Blood. 2015;125(20).
6 Blenrep UK Summary of Product
Characteristics, available at:
https://mhraproducts4853.blob.core.windows.net/docs/6f7040d4dd63fafa1f228164fce767517be4e3c6.