GSK GSK plc

• Overall response rate (ORR) of 31% with 2.5 mg/kg regimen and no new safety signals in heavily pre-treated patient population who were refractory to an immunomodulatory drug and a proteasome inhibitor, and were refractory or intolerant to an anti-CD38 antibody
• Data published in The Lancet Oncology highlight the potential of belantamab mafodotin for patients with multiple myeloma whose disease has progressed
• GSK confirms submission of a Biologics License Application to the US Food and Drug Administration  

LONDON, Dec. 16, 2019 /CNW/ -- GlaxoSmithKline plc (LSE/NYSE: GSK) today announced treatment with the investigational single-agent belantamab mafodotin resulted in a clinically meaningful 31% overall response rate (ORR) with the 2.5 mg/kg regimen in patients with heavily pre-treated multiple myeloma. Patients in the trial received a median of seven prior lines of treatment, were refractory to an immunomodulatory drug and a proteasome inhibitor and were refractory and/or intolerant to an anti-CD38 antibody. The median duration of response has not been reached at six months of follow-up.

Full results from the DREAMM-2 (DRiving Excellence in Approaches to Multiple Myeloma) study of belantamab mafodotin were published today in The Lancet Oncology. GSK also confirmed submission of a Biologics License Application to the US Food and Drug Administration (FDA) seeking approval of belantamab mafodotin for the treatment of patients with relapsed or refractory multiple myeloma whose prior therapy included an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. Belantamab mafodotin is not currently approved for use anywhere in the world.

Dr Hal Barron, Chief Scientific Officer and President R&D, GSK said: "Patients with multiple myeloma whose disease has progressed despite currently available therapy have limited options and poor outcomes. Data from the DREAMM-2 study show that, if approved, belantamab mafodotin could offer an important new treatment option for these patients."

DREAMM-2 is an open label study of belantamab mafodotin, a humanised, immunoconjugate against B-cell maturation antigen (BCMA).ⁱ Patients in the trial had actively progressing multiple myeloma that had worsened despite current standard of care and were randomised to two arms to receive either 2.5 mg/kg or 3.4 mg/kg belantamab mafodotin every three weeks. Overall, patients in DREAMM-2 had more advanced disease, poorer prognosis and performance status and also had a greater number of prior lines of therapy in comparison with patients in DREAMM-1, the first time in human study of belantamab mafodotin.

Dr Sagar Lonial, MD, Chief Medical Officer, Winship Cancer Institute of Emory University, Chair of Emory Department of Hematology and Medical Oncology and Principal Investigator for DREAMM-2, said: "Each day in my practice, I see patients who would benefit from additional therapeutic options because their disease has advanced and is no longer responding to available treatments. In recent years, BCMA has become one of the most promising targets in multiple myeloma research. The data published today from DREAMM-2 not only reinforce the significance of BCMA as a potentially viable target, but also underscore the potential of belantamab mafodotin, if approved, as a practical treatment option in this patient population."

The results demonstrated in DREAMM-2 were consistent with those observed in a similar subset of patients in the DREAMM-1 study. Based on these data, GSK is moving forward with a US FDA submission seeking approval of the 2.5 mg/kg dose. If approved, belantamab mafodotin will be the first anti-BCMA agent available in the US.

Thirty of the 97 patients (31%) in the 2.5 mg/kg cohort achieved an overall response. Of these responders, 18 patients achieved a very good partial response or better, including three patients with stringent complete or complete responses. In addition, overall survival in patients achieving a response was not reached in the six month follow-up period.

The safety and tolerability profile was consistent with previously reported data on belantamab mafodotin. The three most commonly reported Grade 3 or 4 adverse events in the 2.5 mg/kg arm were keratopathy (27%), thrombocytopenia (20%) and anaemia (20%). Keratopathy is characterized as changes in the corneal epithelium as seen on eye examination which can manifest with or without symptoms. Corneal events leading to treatment discontinuation affected 1% of patients in the 2.5 mg/kg cohort.

Additional studies are testing the effect of belantamab mafodotin as third-line monotherapy in relapsed/refractory multiple myeloma and in combination with standard and novel treatments in the first and second line setting as part of the broader DREAMM clinical development programme.

In 2017, GSK2857916 was granted Breakthrough Therapy designation from the US FDA and PRIME designation from the European Medicines Agency.

In the US, an expanded access program for belantamab mafodotin is available to eligible patients with multiple myeloma. For patients to be considered for enrollment in the programme, they must be assessed according to specific inclusion and exclusion criteria by their treating physician. Additional information about the expanded access protocol can be found on ClinicalTrials.gov (NCT03763370).

About multiple myeloma
Multiple myeloma is the second most common blood cancer and is generally considered treatable, but not curable.ⁱⁱ Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.ⁱⁱⁱ

About B-cell maturation antigen (BCMA)
The normal function of BCMA is to promote plasma cell survival by transduction of signals from two known ligands, BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). This pathway has been shown to be important for myeloma cell growth and survival. BCMA expression is limited to B cells at later stages of development. BCMA is expressed at varying levels in myeloma patients and BCMA membrane expression is universally detected in myeloma cell lines.^iv

About the DREAMM clinical trial programme for belantamab mafodotin (GSK2857916)
Belantamab mafodotin is an investigational immunoconjugate comprising a humanised anti-B cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent auristatin F via non-cleavable linker. The drug linker technology is licensed from Seattle Genetics; monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa.

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK's pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics, and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

About GSK
GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.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 'Principal risks and uncertainties' in the company's Annual Report on Form 20-F for 2018.

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References

ⁱ NCI Drug Dictionary - Anti-BCMA Antibody-Drug Conjugate GSK2857916. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/anti-bcma-antibody-drug-conjugate-gsk2857916. Accessed October 2019.
ⁱⁱ 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.
ⁱⁱⁱ Nooka AK, Kastritis E, Dimopoulos MA. Treatment options for relapsed and refractory multiple myeloma. Blood. 2015;125(20)
^iv Carpenter RO, Evbuomwan MO et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013 Apr 15;19(8):2048-60.

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