- DREAMM-7 trial shows sustained overall survival benefit for
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 belantamab mafodotin combinations to become
standard of care
- Belantamab mafodotin 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
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.
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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 randomized, not treated,
rescreened, and rerandomized. 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. (Graphic: GSK)
The OS findings from DREAMM-7 build on previous data from the
DREAMM-71 and DREAMM-82 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 belantamab mafodotin
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 favoring 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 above.
María-Victoria Mateos, MD, PhD, Head of Myeloma and Clinical
Trials Unit, Hematology 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); anemia (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)
0.58 (0.43-0.79)
P-value1
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
NR (45.6-NR)
33.4 (26.7-44.9)
HR
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 US4, European Union5, Japan6 (with
priority review), China (for DREAMM-7 only, with priority review;
Breakthrough Therapy Designation7 also granted), United Kingdom,
Canada and Switzerland (with priority review for DREAMM-8).
About the DREAMM clinical development program
The DREAMM (DRiving Excellence in Approaches to Multiple
Myeloma) clinical development program 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 multi-center,
open-label, randomized 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 randomized 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 center.12,13,14
About belantamab mafodotin
Belantamab mafodotin is an investigational antibody-drug
conjugate comprising a humanized 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.
GSK in oncology
Oncology is an emerging therapeutic area for GSK where we are
committed to maximizing patient survival with a current focus on
hematologic malignancies, gynecologic cancers and other solid
tumors through breakthroughs in immuno-oncology and tumor-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 us.gsk.com.
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
_____________________________________
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 GSK press release issued 02 June 2024. Blenrep combination
reduced the risk of disease progression or death by nearly 50%
versus standard of care combination in relapsed/refractory multiple
myeloma. Available at:
https://www.gsk.com/en-gb/media/press-releases/blenrep-combination-reduced-the-risk-of-disease-progression/.
3 Post hoc analysis using simulation to predict median OS values in
each arm utilising the observed data at the interim analysis with
39.4-month median follow up to extrapolate time to death of ongoing
censored patients. Predicted median OS values subject to change as
data matures. 4 GSK press release issued 25 November 2024. Blenrep
combinations accepted for review by the US FDA for the treatment of
relapsed/refractory multiple myeloma. Available at:
https://www.gsk.com/en-gb/media/press-releases/blenrep-combinations-accepted-for-review-by-the-us-fda-for-the-treatment-of-relapsedrefractory-multiple-myeloma/.
5 GSK press release issued 19 July 2024. Blenrep (belantamab
mafodotin) combinations in multiple myeloma accepted for review by
the European Medicines Agency. Available at:
https://www.gsk.com/en-gb/media/press-releases/blenrep-belantamab-mafodotin-combinations-in-multiple-myeloma-application-accepted-for-review-by-the-european-medicines-agency/.
6 GSK press release issued 17 September 2024. Blenrep (belantamab
mafodotin) combinations in relapsed/refractory multiple myeloma
accepted for regulatory review in Japan. Available at:
https://www.gsk.com/en-gb/media/press-releases/blenrep-belantamab-mafodotin-combinations-in-relapsedrefractory-multiple-myeloma-accepted-for-regulatory-review-in-japan/.
7 GSK press release issued 13 September 2024. Blenrep (belantamab
mafodotin) in combination receives Breakthrough Therapy Designation
in China for treatment of relapsed/refractory multiple myeloma.
Available at:
https://www.gsk.com/en-gb/media/press-releases/blenrep-belantamab-mafodotin-in-combination-receives-breakthrough-therapy-designation-in-china-for-treatment-of-relapsedrefractory-multiple-myeloma/.
8 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. 9 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. 10 Global
Cancer Observatory. International Agency for Research on Cancer.
World Health Organization. Multiple Myeloma fact sheet. Available
at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/35-multiple-myeloma-fact-sheet.pdf.
Accessed 5 July 2024. 11 Nooka AK, Kastritis E, Dimopoulos MA.
Treatment options for relapsed and refractory multiple myeloma.
Blood. 2015;125(20). 12 Information licensed from IQVIA: APLD and
DDD for the period of 2017-Jan. 2024, reflecting estimates of
real-world activity. All rights reserved. 13 Gajra A, Zalenski A,
Sannareddy A, et al. Barriers to Chimeric Antigen Receptor T-Cell
(CAR-T) Therapies in Clinical Practice. Pharmaceut Med. 2022
Jun;36(3):163-171. 14 Crombie J, Graff T, Falchi L, et al.
Consensus recommendations on the management of toxicity associated
with CD3×CD20 bispecific antibody therapy. Blood (2024) 143 (16):
1565–1575.
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