• 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, United Kingdom (Press Release) – 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.

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.

Source: GlaxoSmithKline.