REG - GSK PLC - ASCO positive Blenrep DREAMM-8 trial results

GSKAnnouncement

03/06/2024 07:15

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RNS Number : 7459Q  GSK PLC  03 June 2024

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)  pomalidomide + bortezomib and dexamethasone (PVd)

                                                 (n= 155)                                                     (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), %            64% (55.8-71.4)                                              38% (30.2-46.5)

(95% CI)
 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 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 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 Characteristics
(https://mhraproducts4853.blob.core.windows.net/docs/6f7040d4dd63fafa1f228164fce767517be4e3c6)
(6) 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 enquiries
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 Investor Relations:  Nick Stone         +44 (0) 7717 618834   (London)
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                      Jeff McLaughlin    +1 215 751 7002       (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 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.

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