Belantamab Mafodotin combination reduced the risk of disease progression or death by nearly 50% versus standard of care combination in relapsed/refractory multiple myeloma

Rhea-AI Summary

GSK announced positive interim results from the DREAMM-8 phase III trial, showing that the combination of belantamab mafodotin, pomalidomide, and dexamethasone (PomDex) significantly reduced the risk of disease progression or death by nearly 50% compared to a standard of care combination in relapsed/refractory multiple myeloma. The median progression-free survival (PFS) was not yet reached at a 21.8-month median follow-up for the belantamab mafodotin combination versus 12.7 months for the bortezomib combination. Additionally, the PFS benefit was observed across all pre-specified subgroups, including high-risk patients. Although a positive trend in overall survival (OS) was noted, it was not statistically significant at this interim analysis. Safety profiles were consistent with known profiles of the individual agents, and common adverse events included neutropenia and ocular symptoms. These findings, presented at the 2024 ASCO Annual Meeting and published in the NEJM, support the potential of belantamab mafodotin in redefining treatment for multiple myeloma at or after first relapse.

Positive

• Belantamab mafodotin combination reduced the risk of disease progression or death by nearly 50%.
• Median PFS for belantamab mafodotin combination was not yet reached at 21.8 months versus 12.7 months for the bortezomib combination.
• 71% of patients in the belantamab mafodotin group were alive and had not progressed at the end of one year compared to 51% in the bortezomib group.
• Overall response rate (ORR) for belantamab mafodotin combination was 77% versus 72% for the bortezomib combination.
• Belantamab mafodotin combination showed a higher rate of complete response or better at 40% versus 16% for bortezomib.
• Belantamab mafodotin combination had a higher MRD negativity rate of 23.9% compared to 4.8% for bortezomib.

Negative

• Overall survival (OS) trend for belantamab mafodotin was positive but not statistically significant.
• Grade 3 or higher ocular adverse events occurred in 43% of patients receiving the belantamab mafodotin combination.
• 34% of patients experienced a worsening in visual acuity to 20/50 or worse in both eyes.
• Neutropenia was higher in the belantamab mafodotin combination group (57%) compared to the bortezomib group (39%).
• Pneumonia incidence was higher in the belantamab mafodotin combination group (17%) compared to the bortezomib group (8%).

Insights

Oncology Doctor

The DREAMM-8 phase III trial's results offer significant insights for patients with relapsed/refractory multiple myeloma. The combination of belantamab mafodotin with pomalidomide plus dexamethasone (PomDex) has demonstrated a nearly 50% reduction in the risk of disease progression or death compared to the bortezomib combination, which is substantial. This combination also showed a median progression-free survival (PFS) not yet reached at 21.8 months follow-up, compared to 12.7 months for the bortezomib combination. For patients who have gone through multiple lines of treatment, such an improvement in PFS is critical, as it means prolonged time without disease worsening.

Importantly, the belantamab mafodotin combination benefits pre-specified subgroups, including patients with high-risk cytogenetics and those refractory to lenalidomide, who typically have fewer treatment options and a poorer prognosis.

Medical Research Analyst

The trial data reflect a rigorous evaluation, with strong statistical backing— a hazard ratio (HR) of 0.52 and a p-value of <0.001 indicating robust statistical significance. While these results are promising, they also warrant the need for longer-term overall survival (OS) data, as the trend observed was positive but not statistically significant (HR: 0.77). The interim analysis does show encouraging signs of efficacy across multiple secondary endpoints, like the overall response rate (ORR) of 77% versus 72% and the duration of response with a median not yet reached compared to 17.5 months with the bortezomib combination.

Notably, the belantamab mafodotin combination is associated with manageable ocular adverse events, which led to a 9% treatment discontinuation rate. These were mostly reversible, emphasizing the importance of patient monitoring and potential dose adjustments to maintain treatment efficacy and quality of life.

Financial Analyst

For a retail investor, these results are promising for GSK’s oncology portfolio. A successful phase III trial positions belantamab mafodotin favorably in the competitive multiple myeloma treatment market, an area with substantial demand due to high relapse rates. This could potentially translate to a considerable market share and revenue growth. The simultaneous publication in the New England Journal of Medicine, along with the presentation at ASCO, further validates the credibility and scientific rigor of the study, which can enhance investor confidence.

In the short term, this positive data may boost GSK's stock performance as it indicates potential pipeline strength and future revenue streams. However, investors should also watch regulatory updates and upcoming OS data for a fuller picture of the drug's market potential. The consistency of these results with previous trials (like DREAMM-7) indicates a well-founded strategy for expanding belantamab mafodotin's indications.

• 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 belantamab mafodotin 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

PHILADELPHIA--(BUSINESS WIRE)-- GSK plc (LSE/NYSE: GSK) today announced positive results from an interim analysis of the DREAMM-8 phase III head-to-head trial evaluating 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 (May 31 – June 4) in Chicago, IL, were featured in the official ASCO press program 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 belantamab mafodotin 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% vs 39%; 42 patients/100 person-years in both arms); thrombocytopenia (38% vs 29%; 28 vs 31 patients/100 person-years); and pneumonia (17% vs 8%; 13 vs 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 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. 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 February 6, 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 multi-center, open-label, randomized 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 randomized 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 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 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. Accessed 19 October 2023.
5 Nooka AK, Kastritis E, Dimopoulos MA. Treatment options for relapsed and refractory multiple myeloma. Blood. 2015;125(20).

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FAQ

What were the results of the DREAMM-8 phase III trial for GSK's belantamab mafodotin?

The DREAMM-8 trial showed that the combination of belantamab mafodotin, pomalidomide, and dexamethasone reduced the risk of disease progression or death by nearly 50% compared to a standard care combination in relapsed/refractory multiple myeloma.

How did belantamab mafodotin perform in terms of progression-free survival (PFS) in the DREAMM-8 trial?

Belantamab mafodotin showed a median PFS not yet reached at 21.8 months, compared to 12.7 months for the bortezomib combination, indicating a significant improvement.

What were the overall response rates (ORR) in the DREAMM-8 trial for GSK's belantamab mafodotin combination?

The overall response rate (ORR) for the belantamab mafodotin combination was 77%, compared to 72% for the bortezomib combination.

Did the DREAMM-8 trial show any significant adverse events for GSK's belantamab mafodotin?

Yes, grade 3 or higher ocular adverse events occurred in 43% of patients, and 34% experienced a worsening in visual acuity to 20/50 or worse. Neutropenia and pneumonia were also higher in the belantamab mafodotin group.

What was the significance of the overall survival (OS) trend in the DREAMM-8 trial for GSK's belantamab mafodotin?

A positive overall survival (OS) trend was observed with a hazard ratio of 0.77, but it was not statistically significant at this interim analysis.