At this year’s American Society of Hematology (ASH) meeting, which will be held in early De­cem­ber, more than 100 oral pre­sen­ta­tions and about 400 poster pre­sen­ta­tions will summarize re­search focused on multiple myeloma.

Abstracts for these pre­sen­ta­tions are now avail­able.

During the next several weeks, The Beacon will pub­lish a series of arti­cles pre­viewing the myeloma-related studies from the ASH meeting that are of par­tic­u­lar interest.

Each of the articles will cover abstracts related to a specific topic, such as new treat­ments under de­vel­op­ment, current treat­ments, stem cell trans­plan­ta­tion, prog­nos­tic factors, and the myeloma precursor dis­eases mono­clonal gam­mop­athy of un­de­ter­mined sig­nif­i­cance (MGUS) and smol­der­ing multiple myeloma.

In today's preview article, The Beacon takes a look at the ASH abstracts that report clin­i­cal trial results for a special group of poten­tial new myeloma treat­ments.  The treat­ments covered in today's article are "special" in the sense that they are among the newest poten­tial myeloma ther­a­pies being tested in clin­i­cal trials.

In particular, studies involving a total of eight new treat­ments are covered in this article, in­clud­ing afuresertib (GSK2110183), AT7519M, CUDC-907, IPH 2101, KW-2478, LGH447, NOX-A12, and SAR650984.

The results reported for each drug are based on the preliminary data avail­able in the meeting abstracts.  The drugs with results that seem particularly noteworthy are discussed first in the abstract summaries below.

Before turning to those summaries, it is worth noting that there are two very pos­i­tive aspects to the studies as a whole.

One is the simple fact that this article – which focuses solely on drugs in the very earliest stages of clin­i­cal trial testing – is able to report results for as many as eight different poten­tial new myeloma treat­ments.  Not two or three.  Eight.

The second pos­i­tive aspect of the studies discussed below is that the drugs they are chemically dif­fer­ent from one another and from existing myeloma ther­a­pies such as Revlimid (lena­lido­mide) and Vel­cade (bor­tez­o­mib).

This means that the treat­ments reviewed below offer poten­tial new avenues for the treat­ment of myeloma, which would provide patients and their physicians with genuinely new options for treating the dis­ease.

Now, this pos­i­tive news needs to be bal­anced with the fact that, at this stage, it is dif­fi­cult to assess exactly how promising these newest treat­ments are.  Many of the results below, for example, are from Phase 1 trials.  Such trials usually in­volve­ a small number of patients, and they focus on testing dif­fer­en­t doses of a drug to de­ter­mine its safety and the best dose to use in later trials.

As a result, the re­sponse­ rates seen in Phase 1 trials are quite variable and generally lower than those seen in later (Phase 2 and Phase 3) clin­i­cal trials.

So the good news, rep­re­sented by the sheer number and diversity of the treat­ments discussed below, needs to be tempered with the realization that re­searchers are just beginning to under­stand exactly how promising these new drugs are.

Afuresertib

One of the pre­sen­ta­tions to be made at this year’s ASH meeting will summarize the results of a Phase 1b study of afuresertib (GSK2110183) in com­bi­na­tion with Velcade and dexamethasone (Decadron) for the treat­ment of re­lapsed and re­frac­tory myeloma (abstract).

Afuresertib, which is being devel­oped by the pharma­ceu­tical com­pany GlaxoSmithKline (NYSE: GSK), be­longs to a class of anti-cancer drugs known as Akt-inhibitors. Akt is a protein believed to play an im­por­tant role in the devel­op­ment and growth of cancer cells.  Another Akt in­hib­i­tor that has been tested as a poten­tial myeloma ther­apy is perifosine.

The Phase 1b trial for afuresertib com­bined with Velcade and dexa­meth­a­sone in­cludes 67 myeloma pa­tients who had been treated with a median of 3.5 prior lines of ther­apy.  Most patients had been treated with both pro­te­a­some in­hib­i­tors (such as Velcade) and immuno­modu­la­tory agents (such as Revlimid), with some of the patients being resistant to one or both of those classes of drugs.  The over­all re­sponse­ rate was 41 per­cent, with 3 per­cent of the patients achieving a com­plete re­sponse­, 9 per­cent a very good partial re­sponse­, and 29 per­cent a partial re­sponse­.

Among patients treated at the maximum tolerated dose of 150 mg of afuresertib, 61 per­cent responded. However, none of these patients were resistant to pre­vi­ous Velcade ther­apy.

AT7519M

Results from a Phase 1/2 study to be pre­sented at the ASH meeting will show that AT7519M did not have sig­nif­i­cant activity in re­lapsed and re­frac­tory myeloma patients when used alone.  However, it was clearly active when used in com­bi­na­tion with Velcade (abstract).

AT7519M, which is being devel­oped by Astex Pharma­ceu­ticals (NASDAQ: ASTX), is a cyclin-dependent kinase in­hib­i­tor; it blocks enzymes that are needed for cells to divide.

In part one of the study, nine patients with re­lapsed or re­frac­tory myeloma were treated with AT7519M alone. The treat­ment was well tolerated, but no patients responded (although at least one ex­peri­enced stable dis­ease).

In part two of the study, nine patients who had been treated with a median of five prior lines of ther­apy were treated with AT7519M plus Velcade.  Overall, 33 per­cent of patients responded to the com­bi­na­tion, with 11 per­cent achieving a very good partial re­sponse­ and 22 per­cent achieving a partial re­sponse­.

NOX-A12

A Phase 2a study of NOX-A12 in com­bi­na­tion with Velcade and dexa­meth­a­sone will also be pre­sented at ASH (abstract).

NOX-A12 is being devel­oped by Noxxon Pharma.  NOX-A12 binds to a small molecule called CXCL12 that is known to play a role in drug resistance.

So far, 21 patients who had re­ceived a median of two prior lines of ther­apy have been enrolled in the trial.  Among the nine patients eval­u­ated for re­sponse­, 67 per­cent responded to the com­bi­na­tion of NOX-A12, Velcade, and dexa­meth­a­sone, with 22 per­cent achieving a very good partial re­sponse­ and 44 per­cent achieving a partial re­sponse­.

KW-2478

Researchers will present results from a Phase 1/2 study of KW-2478 plus Velcade for the treat­ment of re­lapsed and re­frac­tory myeloma (abstract).

KW-2478 belongs to a class of anti-myeloma drugs called Hsp90 in­hib­i­tors. The drug is being devel­oped by the Japanese drug manu­fac­turer Kyowa Hakko Kirin. Other Hsp90 in­hib­i­tors that have been in­ves­ti­gated as poten­tial myeloma treat­ments in­clude ganetespib and tanespimycin.

The KW-2478 study in­cluded 95 patients (15 patients in Phase 1 and 80 patients in Phase 2) who had re­ceived one to three prior treat­ment regi­mens; none of the patients were resistant to prior Velcade ther­apy.  Among the 79 patients from Phase 2 of the study who were eval­u­ated for re­sponse­, 39 per­cent responded, with 4 per­cent achieving a com­plete re­sponse­, 14 per­cent a very good partial re­sponse­, and 22 per­cent a partial re­sponse­.  Median pro­gres­sion-free sur­vival was 6 months.

IPH2101

Another pre­sen­ta­tion at the ASH meeting will summarize results from a Phase 1 study of IPH2101 plus Revlimid in re­lapsed myeloma patients (abstract).

IPH2101, which is being devel­oped by Innate Pharma, belongs to the same broad class of drugs as elo­tu­zu­mab and daratumumab, called mono­clonal anti­bodies. Monoclonal anti­bodies work by identifying proteins on the surface of myeloma cells and signal­ing for the immune sys­tem to destroy the cancer cells.  Specifically, IPH2101 activates anti-tumor immune cells known as natural killer cells.

The study in­cludes 15 re­lapsed myeloma patients who had re­ceived one or two pre­vi­ous lines of ther­apy.  Patients could par­tic­i­pate in the trial if they had pre­vi­ously been treated with Revlimid, but not if their dis­ease was con­sidered resistant to Revlimid ther­apy.

Overall, the re­sponse­ rate was 33 per­cent, with 13 per­cent of the patients achieving a very good partial re­sponse­ and 20 per­cent achieving a partial re­sponse­.  The median duration of re­sponse­ was at least 15 months.

SAR650984

Also on the agenda for the ASH meeting will be a pre­sen­ta­tion about another mono­clonal anti­body, SAR650984.  In particular, re­searchers will present results of a Phase 1 study of the drug in patients with re­lapsed or re­frac­tory myeloma or another blood cancer (abstract).

SAR650984 is being devel­oped by the pharma­ceu­tical com­pany Sanofi-Aventis.  The Phase 1 study of the drug in­cludes 32 blood cancer patients who were diag­nosed a median of 6.8 years before study par­tic­i­pa­tion.  Overall, 16 per­cent of patients achieved a partial re­sponse­.  Higher doses of SAR650964 are still being tested.

LGH447

Results of a Phase 1 study of LGH447 in re­lapsed and re­frac­tory myeloma will also be pre­sented at the meeting (abstract).

LGH447 inhibits an enzyme in cancer cells known as PIM kinase, thereby disrupting the cell division cycle and causing cancer cell death.  The drug is being devel­oped by the pharma­ceu­tical com­pany Novartis (NYSE: NVS).

In their abstract for the ASH meeting, the in­ves­ti­ga­tors in­volve­d in the Phase 1 LGH447 trial report that, among the 19 patients treated so far, multiple patients have responded and the best re­sponse­ has been a very good partial re­sponse­.

CUDC-907

Also at ASH, initial results will be pre­sented from a Phase 1 study of CUDC-907 in patients with re­lapsed or re­frac­tory multiple myeloma or lym­phoma (abstract).

CUDC-907, which is being devel­oped by the pharma­ceu­tical com­pany Curis (NASDAQ:CRIS), is a multi-targeted agent that inhibits both PI3K and histone deacetylase (HDAC) in cancer cells.

Other HDAC in­hib­i­tors that are being in­ves­ti­gated as poten­tial treat­ments for multiple myeloma in­clude Zolinza (vorinostat), panobinostat, and ricolinostat (ACY-1215).

At the time of initial analysis, the study in­cluded 6 patients who had re­ceived a median of three prior treat­ment regi­mens; 33 per­cent of the patients had multiple myeloma.  No re­sponse­ results are avail­able yet.

Additional New Therapies Being Studied For Multiple Myeloma

Researchers at the ASH meting also will present results for studies involving several other new agents being studied for the treat­ment of multiple myeloma, in­clud­ing CC-122 (abstract), Cialis (tadalafil) (abstract), PAT-SM6 (abstract), Reolysin (abstract), SNS01-T (abstract), and tivantinib (ARQ197) (abstract).  However, the results for these drugs are not yet particularly promising, with the best re­sponse­s being stable dis­ease.

In most of these cases, the drugs were tested as single agents.  Some of these drugs, such as SNS01-T, are still being tested at higher doses.  Others, such as CC-122, were tested in patients with a variety of can­cers, so the number of myeloma patients was small.  Many of these other drugs may turn out be effective if admin­istered in com­bi­na­tion with other anti-myeloma drugs.  Cialis was added to Revlimid-based reg­i­mens to which patients had pre­vi­ously failed to respond; how­ever, it did not re-sensitize patients to their prior regi­mens.

For in­for­ma­tion about addi­tional studies that will be pre­sented at ASH, see a list of all myeloma-related ASH abstracts, all abstracts about new treat­ments under devel­op­ment for myeloma, clinical trial results for new treat­ments, and preclinical re­search about new treat­ments.