A session last Sunday at the 2015 American Society of Clinical Oncology (ASCO) annual meeting featured a num­ber of poster pre­sen­ta­tions re­lated to mul­ti­ple myeloma.

During “poster sessions” at conferences such as the ASCO meeting, re­search re­­sults are made avail­able for review by meeting attendees in the form of posters, each of which summarizes the re­­sults of a single study. Each poster is typ­i­cally about two feet high by three or four feet in length, and all posters during a ses­sion are dis­played throughout a large conference hall.

Most of the myeloma-related posters at the ASCO session last Sunday focused on re­search re­lated to either cur­rently approved myeloma ther­a­pies or po­ten­tial new myeloma treat­ments. This ASCO 2015 up­date from The Beacon will focus on the posters about po­ten­tial new ther­a­pies.

An earlier ASCO 2015 up­date summarized re­search about ther­a­pies cur­rently approved in the United States for the treat­ment of mul­ti­ple myeloma. It also covered re­search pre­sented during the session that was re­lated to the im­pact of spe­cif­ic chromosomal ab­nor­mal­i­ties, such as del(17p) and t(11;14), on the prog­nosis of myeloma patients (see re­lated Beacon ^[1] news).

Elotuzumab

One of the posters at last Sunday’s session summarized the re­­sults of a Phase 2 trial that com­pared the ef­fi­cacy and safety of two treat­ment regi­mens: elotuzumab in com­bi­na­tion with Velcade (bor­tez­o­mib) and dex­a­meth­a­sone (Decadron); and Velcade ^[2] and dexa­meth­a­sone ^[3] alone (abstract ^[4] #8573).

Elotuzumab ^[5] is being devel­oped by the pharma­ceu­tical com­pa­nies Bristol-Myers Squibb (NYSE: BMY) and AbbVie (NYSE:ABBV).  It belongs to a class of drugs known as mono­clonal anti­bodies. These drugs identify cancer cells through spe­cif­ic pro­teins on the surface of those cells. Once they have identified the cancer cells, the drugs either signal the im­mune sys­tem to attack the cancer cells, or they attack the cells themselves, or they do both (signal and attack on their own).

Elotuzumab, which is given as an in­fusion, targets a pro­tein known as SLAM7 (also known as CS1). The pro­tein is commonly found on the surface of myeloma cells.

The study pre­sented during the ASCO poster session in­cluded 152 myeloma patients with an average age of 64 years who had re­ceived be­tween one to three prior lines of ther­apy. The over­all re­sponse rate was similar be­tween the two treat­ment groups (65 per­cent for elotuzumab, Velcade, and dexa­meth­a­sone, versus 63 per­cent for Velcade and dexa­meth­a­sone alone). Median pro­gres­sion-free sur­vival was longer, how­ever, for patients re­ceiv­ing elotuzumab, Velcade, and dexa­meth­a­sone (9.7 months), com­pared to patient re­ceiv­ing Velcade and dexa­meth­a­sone alone (6.9 months).

The re­searchers also observed a trend for longer over­all sur­vival for patients re­ceiv­ing the elotuzumab com­bi­na­tion. The one-year median over­all sur­vival rate was 85 per­cent for patients re­ceiv­ing elotuzumab, Velcade, and dexa­meth­a­sone versus 74 per­cent for patients re­ceiv­ing Velcade and dexa­meth­a­sone alone.

The most common side effects observed in the patients who re­ceived the three-drug regi­men in­cluded in­fec­tions (65 per­cent), diarrhea (43 per­cent), con­sti­pa­tion (39 per­cent), and cough (39 per­cent). Infusion reac­tions, which may oc­cur with elotuzumab, oc­curred in 7 per­cent of patients and were all mild in nature.

Evofosfamide (TH-302)

Initial re­­sults from a Phase 1 study of evofosfamide ^[11] (TH-302 ^[12]) and dexamethasone with or without Velcade in heavily pre­treated myeloma patients were also pre­sented during the poster session (abstract ^[13] #8579; poster [PDF] ^[14] courtesy of Dr. Jacob Laubach). TH-302 is being devel­oped by Threshold Pharma­ceu­ticals (NASDAQ: THLD) and the German pharma­ceut­i­cal com­pany Merck KGaA for the treat­ment of sev­er­al dif­fer­en­t types of cancer. It is an in­fused drug that is activated under low oxygen level con­di­tions, which are common in solid cancer tumors and in the bone mar­row of people with blood cancers.

The TH-302 study in myeloma thus far has recruited 25 patients. Of those patients, 18 have re­ceived TH-302, Velcade, and dexa­meth­a­sone and have been eval­u­ated for re­sponse. These patients had re­ceived a median of eight prior ther­a­pies.  One of the 18 patients (6 per­cent) achieved a com­plete re­sponse and two (11 per­cent) achieved a partial re­sponse; all of these three patients re­ceived the higher of the two tested dose levels. In addi­tion, one patient (6 per­cent) achieved a minor re­sponse and two patients (11 per­cent) achieved stable dis­ease.  The most common side effects of the treat­ment in­cluded low platelet counts (72 per­cent, anemia (56 per­cent), and nausea (44 per­cent).

MOR202

Another poster summarized the re­­sults of a Phase 1/2b trial of MOR202 ^[15] in re­lapsed and re­frac­tory mul­ti­ple myeloma patients (abstract ^[16] #8574; poster [PDF] ^[17] courtesy of Dr. Marc Raab). MOR202, which is an in­fused drug being devel­oped by the Germany pharma­ceu­tical com­pany MorphoSys, is a mono­clonal anti­body that targets the CD38 pro­tein commonly found on myeloma cells. CD38 is the same pro­tein targeted by dara­tu­mu­mab ^[18] and SAR650984 ^[19], two other mono­clonal anti­bodies also under in­ves­ti­ga­tion as po­ten­tial myeloma ther­a­pies.

At the time the data for the MOR202 poster were analyzed, re­­sults were avail­able for 42 patients, who were treated with single-agent MOR202 at sev­er­al dif­fer­en­t doses. These patients had age of 70 and had re­ceived a median of four prior ther­a­pies, in­clud­ing at least one immuno­modu­la­tory agent, such as Revlimid or tha­lido­mide, and one pro­te­a­some in­hib­i­tor, such as Velcade.

Thus far, one of the 42 patients has responded to treat­ment with single-agent MOR202, achieving a very good partial re­sponse. The most common side effects have in­cluded anemia (33 per­cent), fatigue (33 per­cent), nausea (26 per­cent), low lym­pho­cyte count (19 per­cent), and low white blood cell counts (19 per­cent).

Venetoclax (ABT-199)

Two posters about venetoclax ^[20] (ABT-199 ^[21]) as a po­ten­tial myeloma ther­apy were pre­sented during the ASCO session. Venetoclax is an orally admin­istered drug that targets Bcl-2 and Bcl-2-related pro­teins, which reg­u­late cell death. It is being devel­oped by the U.S. pharma­ceu­tical com­pany AbbVie in col­lab­o­ration with the Swiss pharma­ceu­tical com­pany Roche. Venetoclax has shown good ac­­tiv­ity in pre­clin­i­cal stud­ies, par­ticu­lar­ly in myeloma cells with the chromosomal ab­nor­mal­ity t(11;14).

The first veneto­clax poster summarized the interim re­­sults from a Phase 1 trial of the drug as mono­therapy in re­lapsed and re­frac­tory mul­ti­ple myeloma (abstract ^[22] #8576; poster [PDF] ^[23] courtesy of Dr. Shaji Kumar). So far the trial has recruited 29 patients with a median age of 66 years who had re­ceived a median of six prior ther­a­pies. Almost half of the patients (41 per­cent) had t(11;14)-positive myeloma cells; 18 per­cent of these patients responded with a com­plete re­sponse. Best re­sponse among patients without t(11;14) was stable dis­ease. The most common side effects in­cluded diarrhea (41 per­cent), nausea (41 per­cent), fatigue (24 per­cent), and vomiting (24 per­cent).

The sec­ond poster reported findings from a Phase 1b trial of veneto­clax in com­bi­na­tion with Velcade and dexa­meth­a­sone in re­lapsed and re­frac­tory myeloma (abstract ^[24] #8580; poster [PDF] ^[25] courtesy of Dr. Cyrille Touzeau). So far, 38 patients with a median age of 65 years who re­ceived a median of five prior ther­a­pies have been en­rolled in the trial. Over­all 47 per­cent of patients achieved a partial re­sponse or better with the veneto­clax com­bi­na­tion. These re­sponses, how­ever, were only observed in patients who were not resistant (refractory) to Velcade, or had never been treated with Velcade. The best re­sponse observed in patients who were resistant to Velcade was a minor re­sponse. The most common side effects in­cluded con­sti­pa­tion (37 per­cent), diarrhea (32 per­cent), low platelet counts (29 per­cent), and periph­eral neu­rop­athy (26 per­cent).

CUDC-907

Another poster during the ASCO session pre­sented re­­sults of a Phase 1 trial of CUDC-907 ^[26] in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma or lym­phoma (abstract ^[27] #8537; poster [PDF] ^[28] courtesy of Dr. Jesus Berdeja). CUDC-907, which is being devel­oped by the pharma­ceu­tical com­pany Curis (NASDAQ:CRIS), is an orally admin­istered drug that in­hib­its both PI3K and histone deacetylase (HDAC) enzymes.

Farydak ^[29] (panobinostat) was the first HDAC in­hib­i­tor approved to treat mul­ti­ple myeloma. Other HDAC in­hib­i­tors that have been – or cur­rently are being – in­ves­ti­gated as po­ten­tial myeloma ther­a­pies in­clude Zolinza ^[30] (vorinostat), and ricolinostat ^[31] (ACY-1215 ^[32]).

Perifosine ^[33], a com­bined Akt and PI3k in­hib­i­tor, was once in clin­i­cal trials as a po­ten­tial myeloma ther­apy, but its de­vel­op­ment has been halted. Zydelig (idelalisib), the first PI3K in­hib­i­tors approved as a cancer ther­apy, is used in the treat­ment of cer­tain types of leukemia and lym­phoma. It also was tested as a treat­ment for mul­ti­ple myeloma in an early stage clin­i­cal trial, but re­­sults of that study were never pub­lished. Other PI3k in­hib­i­tors are cur­rently being in­ves­ti­gated as po­ten­tial blood cancer ther­a­pies, primarily leukemia and lym­phoma.

The CUDC-907 study pre­sented at ASCO in­cluded 57 patients who had re­ceived a median of five prior treat­ment regi­mens. Patients in the trial re­ceived single-agent CUDC-907. Several dif­fer­en­t doses of the drug were tested, as were sev­er­al dif­fer­en­t dosing frequencies.

Nine patients in the study had mul­ti­ple myeloma. Among these nine patients, one responded, achieving a minor re­sponse; three patients achieved stable dis­ease for at least a short period of time; and three patients have re­­sults that are not yet evaluable. One of the three patients who achieved stable dis­ease is still stable two years after start­ing treat­ment with CUDC-907.

Across all patients in the study, the most common side effects in­cluded diarrhea, fatigue, nausea, and low platelet counts.

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For all Beacon articles re­lated to this year’s ASCO meeting, see The Beacon’s full ASCO 2015 ^[10] coverage. In addi­tion, The Beacon has com­plete lists of all ASCO 2015 myeloma-related oral pre­sen­ta­tions ^[6], poster pre­sentations ^[7], education session pre­sen­ta­tions ^[9], and e-abstracts ^[8].