REG - GSK PLC - Overall survival data presented for Blenrep

GSKAnnouncement

09/12/2024 18:30

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RNS Number : 2296P  GSK PLC  09 December 2024

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 66(th) American Society of
Hematology (ASH) Annual Meeting and Exposition.

 

The OS findings from DREAMM-7 build on previous data from the DREAMM-7
(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/)
 1  (#_edn1) and DREAMM-8
(https://www.gsk.com/en-gb/media/press-releases/blenrep-combination-reduced-the-risk-of-disease-progression/)
 2  (#_edn2) 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  (#_edn3)

 

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 +             daratumumab +
                                                                                 bortezomib + dexamethasone (BVd)   bortezomib + dexamethasone (DVd)

                                                                                 n=243                              n=251
 OS (overall survival), HR (95% CI)                                              0.58 (0.43-0.79)

 P-value(1)
                                                                                                                    p=
                                                                                                                    0.
                                                                                                                    00
                                                                                                                    02
                                                                                                                    3
 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,  25.1% (19.8-31.0)                  10.4% (6.9-14.8)
 % (95% CI)

 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
                                                                                                                    .4
                                                                                                                    5
                                                                                                                    -0
                                                                                                                    .7
                                                                                                                    7)

(1)One-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
(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/)
 4  (#_edn4) , European Union
(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/)
(( 5  (#_edn5) )), Japan
(https://www.gsk.com/en-gb/media/press-releases/blenrep-belantamab-mafodotin-combinations-in-relapsedrefractory-multiple-myeloma-accepted-for-regulatory-review-in-japan/)
(( 6  (#_edn6) )) (with priority review), China (for DREAMM-7 only, with
priority review; Breakthrough Therapy Designation
(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/)
(( 7  (#_edn7) )) 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 presented
(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/)
(1) 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  (#_edn8) (, 9  (#_edn9) )
There are approximately more than 180,000 new cases of multiple myeloma
diagnosed globally each year. 10  (#_edn10) Research into new therapies is
needed as multiple myeloma commonly becomes refractory to available
treatments. 11  (#_edn11) 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  (#_edn12)
(, 13  (#_edn13) , 14  (#_edn14) )

 

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.

 

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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 Q3 Results for 2024.

 

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WC1A 1DG

 1  (#_ednref1) 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  (#_ednref2) 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  (#_ednref3) 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  (#_ednref4) 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  (#_ednref5) 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  (#_ednref6) 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  (#_ednref7) 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  (#_ednref8) 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  (#_ednref9) 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  (#_ednref10) 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  (#_ednref11) Nooka AK, Kastritis E, Dimopoulos MA. Treatment options for
relapsed and refractory multiple myeloma. Blood. 2015;125(20).

 12  (#_ednref12) Information licensed from IQVIA: APLD and DDD for the period
of 2017-Jan. 2024, reflecting estimates of real-world activity. All rights
reserved.

 13  (#_ednref13) 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  (#_ednref14) 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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